{"id":2901,"date":"2026-07-14T17:27:32","date_gmt":"2026-07-14T17:27:32","guid":{"rendered":"https:\/\/www.merckconnect.com\/ohtuvayre\/?page_id=2901"},"modified":"2026-08-12T15:27:02","modified_gmt":"2026-08-12T15:27:02","slug":"clinical-data-study-design","status":"publish","type":"page","link":"https:\/\/www.merckconnect.com\/ohtuvayre\/clinical-data-study-design\/","title":{"rendered":"Study design"},"content":{"rendered":"\n\n
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OHTUVAYRE TRIALS EVALUATED<\/strong><\/mark><\/p>

Lung function, safety, and \u2028health-related quality of life<\/h1>

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Study design<\/a> |<\/strong><\/p>\n<\/div>\n\n\n\n

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Primary endpoint<\/a> |<\/strong><\/p>\n<\/div>\n\n\n\n

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Secondary endpoints<\/a><\/strong><\/p>\n<\/div>\n<\/div>\n\n\n\n

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Study design<\/h2><\/div>\n\n\n\n
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The ENHANCE studies were pivotal phase 3 trials that enrolled a broad population of symptomatic adult patients with moderate to severe COPD1<\/sup><\/h3><\/div>\n\n\n\n
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Graph Secondary Endpoints improvement<\/title>The graphic shows a bar graph of parallel-group clinical trials: ENHANCE-1 and ENHANCE-2 spanning 24 weeks. A subset of ENHANCE-1 patients was evaluated for 48 weeks.\n\nThe graphic depicts a horizontal x-axis with text markers and dotted lines of 0 weeks, 12 weeks, 24 weeks, and 48 weeks. In between the 24 weeks and 48 weeks text markers is the title, \u201cENHANCE-1 Safety Cohort.\u201d The vertical y-axis labels the ENHANCE-1 N=763, R 5:3, in navy blue, and ENHANCE-2 N=790, R 5:3, in purple. \n\nThe top bar on the x-axis is in the ENHANCE-1 navy blue category and is navy blue in color. It is labeled \u201cOHTUVAYRE 3 mg BID n=477b\u201d and begins at zero weeks and ends at 48 weeks. The bar originates at 0 weeks, reaches as a solid bar to 24 weeks, then extends further as a thinner bar from 24 to 48 weeks. The second to top bar on the x-axis is in the ENHANCE-1 navy blue category and is gray in color. It is labeled \u201cPlacebo BID n=282b\u201d and begins at zero weeks and ends at 48 weeks. The bar originates at 0 weeks, reaches as a solid bar to 24 weeks, then extends further as a thinner bar from 24 to 48 weeks. \n\nThe third bar from the top on the x-axis is in the ENHANCE-2 purple category and is purple in color. It is labeled \u201cOHTUVAYRE 3 mg BID n=498b\u201d and begins at zero weeks and ends at 24 weeks. The fourth bar from the top on the x-axis is in the ENHANCE-2 purple category and is gray in color. It is labeled \u201cPlacebo BID n=291b\u201d and begins at zero weeks and ends at 24 weeks.<\/desc><\/path><\/line><\/rect><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/mask><\/path><\/g><\/path><\/mask><\/path><\/g><\/path><\/line><\/line><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/g><\/line><\/rect><\/rect><\/path><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/path><\/clipPath><\/path><\/clipPath><\/defs><\/svg> <\/div><\/div>
Graph Secondary Endpoints improvement<\/title>The graphic shows a bar graph of parallel-group clinical trials: ENHANCE-1 and ENHANCE-2 spanning 24 weeks. A subset of ENHANCE-1 patients was evaluated for 48 weeks.\n\nThe graphic depicts a horizontal x-axis with text markers and dotted lines of 0 weeks, 12 weeks, 24 weeks, and 48 weeks. In between the 24 weeks and 48 weeks text markers is the title, \u201cENHANCE-1 Safety Cohort.\u201d The vertical y-axis labels the ENHANCE-1 N=763, R 5:3, in navy blue, and ENHANCE-2 N=790, R 5:3, in purple. \n\nThe top bar on the x-axis is in the ENHANCE-1 navy blue category and is navy blue in color. It is labeled \u201cOHTUVAYRE 3 mg BID n=477b\u201d and begins at zero weeks and ends at 48 weeks. The bar originates at 0 weeks, reaches as a solid bar to 24 weeks, then extends further as a thinner bar from 24 to 48 weeks. The second to top bar on the x-axis is in the ENHANCE-1 navy blue category and is gray in color. It is labeled \u201cPlacebo BID n=282b\u201d and begins at zero weeks and ends at 48 weeks. The bar originates at 0 weeks, reaches as a solid bar to 24 weeks, then extends further as a thinner bar from 24 to 48 weeks. \n\nThe third bar from the top on the x-axis is in the ENHANCE-2 purple category and is purple in color. It is labeled \u201cOHTUVAYRE 3 mg BID n=498b\u201d and begins at zero weeks and ends at 24 weeks. The fourth bar from the top on the x-axis is in the ENHANCE-2 purple category and is gray in color. It is labeled \u201cPlacebo BID n=291b\u201d and begins at zero weeks and ends at 24 weeks.<\/desc><\/path><\/line><\/rect><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/mask><\/path><\/g><\/path><\/mask><\/path><\/g><\/path><\/line><\/line><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/g><\/line><\/rect><\/rect><\/path><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/path><\/clipPath><\/path><\/clipPath><\/defs><\/svg> <\/div><\/div>
Graph Secondary Endpoints improvement_Mobile<\/title>The graphic shows a bar graph of parallel-group clinical trials: ENHANCE-1 and ENHANCE-2 spanning 24 weeks. A subset of ENHANCE-1 patients was evaluated for 48 weeks.\n\nThe graphic depicts a horizontal x-axis with text markers and dotted lines of 0 weeks, 12 weeks, 24 weeks, and 48 weeks. In between the 24 weeks and 48 weeks text markers is the title, \u201cENHANCE-1 Safety Cohort.\u201d The vertical y-axis labels the ENHANCE-1 N=763, R 5:3, in navy blue, and ENHANCE-2 N=790, R 5:3, in purple. \n\nThe top bar on the x-axis is in the ENHANCE-1 navy blue category and is navy blue in color. It is labeled \u201cOHTUVAYRE 3 mg BID n=477b\u201d and begins at zero weeks and ends at 48 weeks. The bar originates at 0 weeks, reaches as a solid bar to 24 weeks, then extends further as a thinner bar from 24 to 48 weeks. The second to top bar on the x-axis is in the ENHANCE-1 navy blue category and is gray in color. It is labeled \u201cPlacebo BID n=282b\u201d and begins at zero weeks and ends at 48 weeks. The bar originates at 0 weeks, reaches as a solid bar to 24 weeks, then extends further as a thinner bar from 24 to 48 weeks. \n\nThe third bar from the top on the x-axis is in the ENHANCE-2 purple category and is purple in color. It is labeled \u201cOHTUVAYRE 3 mg BID n=498b\u201d and begins at zero weeks and ends at 24 weeks. The fourth bar from the top on the x-axis is in the ENHANCE-2 purple category and is gray in color. It is labeled \u201cPlacebo BID n=291b\u201d and begins at zero weeks and ends at 24 weeks.<\/desc><\/rect><\/rect><\/rect><\/path><\/rect><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/line><\/line><\/line><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/svg> <\/div><\/div><\/div><\/div><\/div><\/div>\n\n\n\n
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a<\/sup>N, number of all enrolled patients.<\/p>\n\n\n\n

b<\/sup>n, number of patients who received at least one dose of study drug and had non-missing FEV1<\/sub> value.<\/p>\n<\/div><\/div><\/div>\n\n\n\n

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Safety of OHTUVAYRE was based on the pooled safety population for 24 weeks in ENHANCE-1 and ENHANCE-2 and on a 48-week cohort (OHTUVAYRE, n=280; placebo, n=89) in ENHANCE-1.<\/strong><\/h4><\/div>\n<\/div><\/div><\/div>\n\n\n\n
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Overview<\/h3><\/div>\n\n\n\n
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The ENHANCE Trials were designed to evaluate the efficacy and safety of OHTUVAYRE in patients with moderate to severe COPD in two 24-week randomized, double-blind, placebo-controlled, parallel-group clinical studies. After a 28-day run-in to ensure stable background medication use, a total of 1553 adults (763 in ENHANCE-1, 790 in ENHANCE-2) were randomized 5:3 to receive 3 mg of OHTUVAYRE or placebo twice daily administered by oral inhalation via standard jet nebulizer.1<\/sup><\/p>\n\n\n\n

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ENHANCE-1<\/strong><\/h4><\/summary>
The ENHANCE-1 trial enrolled a total of 763 patients randomized to receive 3 mg of OHTUVAYRE or placebo twice daily administered by oral inhalation via standard jet nebulizer. A total of 68% of patients were taking concurrent therapy: 30% taking concurrent LAMA, 18% taking concurrent LABA, and 20% taking concurrent LABA\/ICS therapy throughout the trial. A subset of patients was evaluated for 48 weeks.<\/span><\/div><\/details><\/div>\n\n\n\n

ENHANCE-2<\/strong><\/h4><\/summary>
The ENHANCE-2 trial enrolled a total of 790 patients randomized to receive 3 mg of OHTUVAYRE or placebo twice daily administered by oral inhalation via standard jet nebulizer. A total of 55% of patients were taking concurrent therapy: 33% taking concurrent LAMA, 7% taking concurrent LABA, and 15% taking concurrent LABA\/ICS therapy throughout the trial.<\/span><\/div><\/details><\/div>\n\n\n\n
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Patients were allowed to remain in the trials after treatment discontinuation.1<\/sup><\/p>\n\n\n\n

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c<\/sup>Selected inclusion\/exclusion criteria.
BID, twice daily; COPD, chronic obstructive pulmonary disease; ENHANCE, E<\/strong>nsifentrine as a N<\/strong>ovel inHA<\/strong>led N<\/strong>ebulized C<\/strong>OPD thE<\/strong>rapy; FEV1<\/sub>, forced expiratory volume in one second; FVC, forced vital capacity; ICS, inhaled corticosteroids; LABA, long-acting beta2<\/sub>-agonist; LAMA, long-acting muscarinic antagonist; mMRC, modified Medical Research Council dyspnea scale; R, randomization.<\/p>\n\n\n\n

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Patients1<\/sup><\/h3><\/div>\n\n\n\n
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Selected eligibility criteriac<\/sup>:<\/strong><\/p>\n\n\n\n

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  • COPD diagnosis: FEV1<\/sub>\/FVC<0.71<\/sup><\/li>\n\n\n\n
  • Post-bronchodilator FEV1<\/sub> 30-70% predicted normal1<\/sup><\/li>\n\n\n\n
  • mMRC dyspnea scale score \u226521<\/sup><\/li>\n\n\n\n
  • Current smoker or smoking history (\u226510 pack-years)1<\/sup><\/li>\n\n\n\n
  • No asthma diagnosis1<\/sup><\/li>\n\n\n\n
  • No exacerbation requiring oral or parenteral steroids in the 3 months prior to screening1,2<\/sup><\/li>\n<\/ul>\n<\/div>\n\n\n\n
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    Selected baseline characteristics:<\/strong><\/p>\n\n\n\n

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    • Approximately 62% of patients were on maintenance background therapy, which primarily included LAMA, LABA, or LABA + ICS1<\/sup><\/li>\n\n\n\n
    • ~38% weren’t currently on concomitant maintenance COPD therapy1<\/sup><\/li>\n\n\n\n
    • In the ENHANCE-1 and ENHANCE-2 trials, 25% and 21% of patients, respectively, reported exacerbations of COPD within the 15 months prior to the studies<\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n\n\n\n
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      Primary endpoint<\/h3><\/div>\n\n\n\n
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      Change from baseline in FEV1<\/sub> AUC0-12h<\/sub> post dose at Week 12a<\/sup><\/p>\n\n\n\n

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      Selected key secondary endpoints<\/h3><\/div>\n\n\n\n
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      The ENHANCE trials were powered to statistically test secondary endpoints in a hierarchical order, including the selected endpoints below:<\/strong><\/p>\n\n\n\n

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      • Change from baseline in peak FEV1<\/sub> at Week 121,b<\/sup><\/li>\n\n\n\n
      • Change from baseline in SGRQ total score at Week 241,c<\/sup><\/li>\n\n\n\n
      • SGRQ responder rates at Week 24c<\/sup><\/li>\n<\/ul>\n<\/div>\n\n\n\n
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        Selected other endpoints<\/h3><\/div>\n\n\n\n
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        These endpoints were not part of the formal testing hierarchy and therefore were not evaluated for statistical significance. Therefore, no conclusions can be drawn.1<\/sup><\/strong><\/p>\n\n\n\n

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        • Change from baseline in peak FEV1<\/sub> at different timepoints (Day 1, Week 6, Week 12, and Week 24)3,4,b,c<\/sup><\/li>\n\n\n\n
        • Change from baseline in SGRQ total score at different timepoints (Week 6, Week 12, and Week 24)3,4,c<\/sup><\/li>\n\n\n\n
        • TDI at different timepoints (Week 6, Week 12, and Week 24)1<\/sup><\/li>\n\n\n\n
        • Moderate\/severe exacerbation risk over 24 weeks and 48 weeks1,d<\/sup><\/li>\n<\/ul>\n<\/div>\n\n\n\n
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          To address multiplicity in the analysis of the endpoints, statistical testing of the primary endpoint and selected key secondary endpoints was conducted in a hierarchical order.1,5<\/sup> As the pre-specified hierarchical testing criteria were not fully met in ENHANCE-2, SGRQ total score and proportion of SGRQ responders at Week 24 were not formally tested for statistical significance.1,6<\/sup><\/strong><\/p><\/div><\/div>\n\n\n\n

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          a<\/sup>Average FEV1<\/sub> AUC0-12h<\/sub> is defined as the AUC over 12 hours of the FEV1<\/sub>, divided by 12 hours.1<\/sup>
          b<\/sup>Peak FEV1<\/sub> was defined as the highest post-dose FEV1<\/sub> within the first 4 hours after dosing.1<\/sup>
          c<\/sup>SGRQ is a patient-reported measure of symptoms, activity, and impacts on daily life and perceived well-being in patients with obstructive airway disease.7<\/sup><\/p>\n\n\n\n

          d<\/sup>Moderate COPD exacerbations were defined as worsening of COPD symptoms requiring 2 or more major symptoms or one major symptom and one minor symptom for 2 or more days requiring a minimum of 3 days of therapy with oral or systemic corticosteroids and\/or antibiotics; severe COPD exacerbations were defined as worsening of symptoms and inpatient hospitalization.1<\/sup>
          AUC, area under the curve; FEV1<\/sub>, forced expiratory volume in one second; SGRQ, St. George\u2019s Respiratory Questionnaire; TDI, transition dyspnea index.<\/p><\/div><\/div>\n<\/div>\n<\/div>\n\n\n\n

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          Primary endpoint<\/strong><\/p><\/div><\/div>\n\n\n\n

          Change from baseline in FEV1<\/sub> AUC0-12h<\/sub> at Week 12a<\/sup><\/strong><\/h2><\/div>\n\n\n\n
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          Significantly improved lung function as demonstrated by average FEV1<\/sub> AUC0-12h<\/sub><\/strong><\/h3><\/div>\n\n\n\n
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          Graph Primary Endpoint<\/title>The vertical y-axis of this graph is labeled, \u201cLS Mean Change from Baseline FEV1 AUCo-12h(mL).\u201d The y-axis numbers begin at -60 from the bottom of the graph and end at 80 at the top of the graph, counting up from -60 to 80 in increments of ten. The horizontal x-axis label of the graph gives two different title labels to four bar graphs, two of which are grouped under the title \u201cENHANCE-1\u201d on a navy blue background with white text, and two of which are grouped under the title \u201cENHANCE-2\u201d on a purple background with white text. Underneath the graph is a color label. Solid gray color indicates Placebo bars, and a light blue to dark blue gradient color indicates OHTUVAYRE bars.\n\nThe first bar under the ENHANCE-1 grouping is labeled, \u201cPlacebo (n=282)b\u201d. This placebo bar is colored in solid gray. Within the solid gray placebo bar illustration is the number \u201c-26\u201d in white text on the gray color of the bar. The ENHANCE-1 gray placebo bar begins at zero (of the y-axis) and extends downward to slightly more than halfway between -20 and -30 positions on the y-axis, illustrating its -26 position. The second bar, to its right, within the ENHANCE-1 grouping, is a light blue to dark blue gradient colored bar labeled, \u201cOHTUVAYRE (n=477)b\u201d. Within the blue gradient OHTUVAYRE bar illustration is the number \u201c61\u201d in white text on the gradient blue color of the bar. The ENHANCE-1 blue OHTUVAYRE bar begins at zero and extends upwards to just above the 60 position on the y-axis, illustrating its 61 position. \nIn between the placebo bar and the OHTUVAYRE bar is a dotted line, extending from the -26 position upwards to the 61 position. Toward the top portion of this dotted line is a callout bubble, with a light purple background and dark purple text. The text reads, \u201c+87 mL LS Mean Difference from Placebo p<0.0001.\u201d\n\nThe third bar on this graph, which is underneath the ENHANCE-2 grouping is labeled, \u201cPlacebo (n=291)b.\u201d This placebo bar is colored in solid gray. Within the solid gray placebo bar illustration is the number \u201c-46\u201d in white text on the gray color of the bar. The ENHANCE-2 placebo bar begins at zero (of the y-axis) and extends downward to slightly more than halfway between -40 and -50 positions on the y-axis, illustrating its -46 position. The fourth bar on this graph, to its right, within the ENHANCE-2 grouping, is a light blue to dark blue gradient colored bar labeled, \u201cOHTUVAYRE (n=498)b\u201d. Within the blue gradient OHTUVAYRE bar illustration is the number \u201c48\u201d in white text on the gradient blue color of the bar. The ENHANCE-2 OHTUVAYRE bar begins at zero and extends upwards to just below the 50 position on the y-axis, illustrating its 48 position. In between the placebo bar and the OHTUVAYRE bar is a dotted line, extended from the -46 position upwards to the 48 position. Toward the top portion of this dotted line is a callout bubble, with a light purple background and dark purple text. The text reads, \u201c+94 mL LS Mean Difference from Placebo p<0.0001.\u201d<\/desc><\/rect><\/path><\/mask><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/mask><\/path><\/path><\/g><\/path><\/path><\/path><\/mask><\/path><\/g><\/path><\/path><\/path><\/mask><\/path><\/g><\/path><\/path><\/mask><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feComposite><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feComposite><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/rect><\/clipPath><\/defs><\/svg> <\/div><\/div>
          Graph Primary Endpoint<\/title>The vertical y-axis of this graph is labeled, \u201cLS Mean Change from Baseline FEV1 AUCo-12h(mL).\u201d The y-axis numbers begin at -60 from the bottom of the graph and end at 80 at the top of the graph, counting up from -60 to 80 in increments of ten. The horizontal x-axis label of the graph gives two different title labels to four bar graphs, two of which are grouped under the title \u201cENHANCE-1\u201d on a navy blue background with white text, and two of which are grouped under the title \u201cENHANCE-2\u201d on a purple background with white text. Underneath the graph is a color label. Solid gray color indicates Placebo bars, and a light blue to dark blue gradient color indicates OHTUVAYRE bars.\n\nThe first bar under the ENHANCE-1 grouping is labeled, \u201cPlacebo (n=282)b\u201d. This placebo bar is colored in solid gray. Within the solid gray placebo bar illustration is the number \u201c-26\u201d in white text on the gray color of the bar. The ENHANCE-1 gray placebo bar begins at zero (of the y-axis) and extends downward to slightly more than halfway between -20 and -30 positions on the y-axis, illustrating its -26 position. The second bar, to its right, within the ENHANCE-1 grouping, is a light blue to dark blue gradient colored bar labeled, \u201cOHTUVAYRE (n=477)b\u201d. Within the blue gradient OHTUVAYRE bar illustration is the number \u201c61\u201d in white text on the gradient blue color of the bar. The ENHANCE-1 blue OHTUVAYRE bar begins at zero and extends upwards to just above the 60 position on the y-axis, illustrating its 61 position. \nIn between the placebo bar and the OHTUVAYRE bar is a dotted line, extending from the -26 position upwards to the 61 position. Toward the top portion of this dotted line is a callout bubble, with a light purple background and dark purple text. The text reads, \u201c+87 mL LS Mean Difference from Placebo p<0.0001.\u201d\n\nThe third bar on this graph, which is underneath the ENHANCE-2 grouping is labeled, \u201cPlacebo (n=291)b.\u201d This placebo bar is colored in solid gray. Within the solid gray placebo bar illustration is the number \u201c-46\u201d in white text on the gray color of the bar. The ENHANCE-2 placebo bar begins at zero (of the y-axis) and extends downward to slightly more than halfway between -40 and -50 positions on the y-axis, illustrating its -46 position. The fourth bar on this graph, to its right, within the ENHANCE-2 grouping, is a light blue to dark blue gradient colored bar labeled, \u201cOHTUVAYRE (n=498)b\u201d. Within the blue gradient OHTUVAYRE bar illustration is the number \u201c48\u201d in white text on the gradient blue color of the bar. The ENHANCE-2 OHTUVAYRE bar begins at zero and extends upwards to just below the 50 position on the y-axis, illustrating its 48 position. In between the placebo bar and the OHTUVAYRE bar is a dotted line, extended from the -46 position upwards to the 48 position. Toward the top portion of this dotted line is a callout bubble, with a light purple background and dark purple text. The text reads, \u201c+94 mL LS Mean Difference from Placebo p<0.0001.\u201d<\/desc><\/rect><\/path><\/mask><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/mask><\/path><\/path><\/g><\/path><\/path><\/path><\/mask><\/path><\/g><\/path><\/path><\/path><\/mask><\/path><\/g><\/path><\/path><\/mask><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feComposite><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feComposite><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/rect><\/clipPath><\/defs><\/svg> <\/div><\/div>
          Graph Primary Endpoint_Mobile<\/title>The vertical y-axis of this graph is labeled, \u201cLS Mean Change from Baseline FEV1 AUCo-12h(mL).\u201d The y-axis numbers begin at -60 from the bottom of the graph and end at 80 at the top of the graph, counting up from -60 to 80 in increments of ten. The horizontal x-axis label of the graph gives two different title labels to four bar graphs, two of which are grouped under the title \u201cENHANCE-1\u201d on a navy blue background with white text, and two of which are grouped under the title \u201cENHANCE-2\u201d on a purple background with white text. Underneath the graph is a color label. Solid gray color indicates Placebo bars, and a light blue to dark blue gradient color indicates OHTUVAYRE bars.\n\nThe first bar under the ENHANCE-1 grouping is labeled, \u201cPlacebo (n=282)b\u201d. This placebo bar is colored in solid gray. Within the solid gray placebo bar illustration is the number \u201c-26\u201d in white text on the gray color of the bar. The ENHANCE-1 gray placebo bar begins at zero (of the y-axis) and extends downward to slightly more than halfway between -20 and -30 positions on the y-axis, illustrating its -26 position. The second bar, to its right, within the ENHANCE-1 grouping, is a light blue to dark blue gradient colored bar labeled, \u201cOHTUVAYRE (n=477)b\u201d. Within the blue gradient OHTUVAYRE bar illustration is the number \u201c61\u201d in white text on the gradient blue color of the bar. The ENHANCE-1 blue OHTUVAYRE bar begins at zero and extends upwards to just above the 60 position on the y-axis, illustrating its 61 position. \nIn between the placebo bar and the OHTUVAYRE bar is a dotted line, extending from the -26 position upwards to the 61 position. Toward the top portion of this dotted line is a callout bubble, with a light purple background and dark purple text. The text reads, \u201c+87 mL LS Mean Difference from Placebo p<0.0001.\u201d\n\nThe third bar on this graph, which is underneath the ENHANCE-2 grouping is labeled, \u201cPlacebo (n=291)b.\u201d This placebo bar is colored in solid gray. Within the solid gray placebo bar illustration is the number \u201c-46\u201d in white text on the gray color of the bar. The ENHANCE-2 placebo bar begins at zero (of the y-axis) and extends downward to slightly more than halfway between -40 and -50 positions on the y-axis, illustrating its -46 position. The fourth bar on this graph, to its right, within the ENHANCE-2 grouping, is a light blue to dark blue gradient colored bar labeled, \u201cOHTUVAYRE (n=498)b\u201d. Within the blue gradient OHTUVAYRE bar illustration is the number \u201c48\u201d in white text on the gradient blue color of the bar. The ENHANCE-2 OHTUVAYRE bar begins at zero and extends upwards to just below the 50 position on the y-axis, illustrating its 48 position. In between the placebo bar and the OHTUVAYRE bar is a dotted line, extended from the -46 position upwards to the 48 position. Toward the top portion of this dotted line is a callout bubble, with a light purple background and dark purple text. The text reads, \u201c+94 mL LS Mean Difference from Placebo p<0.0001.\u201d<\/desc><\/rect><\/path><\/mask><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/mask><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/mask><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feComposite><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/feFlood><\/feColorMatrix><\/feOffset><\/feGaussianBlur><\/feComposite><\/feColorMatrix><\/feBlend><\/feBlend><\/filter><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/rect><\/clipPath><\/rect><\/clipPath><\/defs><\/svg> <\/div><\/div><\/div><\/div>\n\n\n\n
          <\/div>\n<\/div>\n\n\n\n

          a<\/sup>Average FEV1<\/sub> AUC0-12h<\/sub> is defined as the AUC over 12 hours of the FEV1<\/sub>, divided by 12 hours.1<\/sup>
          b<\/sup>n, number of patients who received at least one dose of study drug and had non-missing baseline FEV1<\/sub> value.<\/p>\n\n\n\n

          AUC, area under the curve; ENHANCE, E<\/strong>nsifentrlne as a N<\/strong>ovel inHA<\/strong>led N<\/strong>ebulized C<\/strong>OPD thE<\/strong>rapy; FEV1<\/sub>, forced expiratory volume in one second; mL, milliliter.<\/p>\n\n\n\n

          <\/div>\n<\/div><\/div><\/div>\n\n\n\n
          <\/div>\n\n\n\n
          \n\n\n\n
          <\/div>\n\n\n\n
          \n

          Selected key secondary endpoints<\/strong><\/h4><\/div>\n\n\n\n

          Peak FEV1 <\/sub>at Week 121,3,4,8<\/sup><\/strong><\/h2><\/div>\n\n\n\n

          Key secondary endpoint: <\/strong>Peak FEV1<\/sub> evaluated at Week 12 was included in the statistical testing hierarchy.1<\/sup><\/p>\n\n\n\n

          Limitations:<\/strong> Peak FEV1<\/sub> at Day 1, Week 6, and Week 24 were not included in the statistical hierarchy for ENHANCE-1 and ENHANCE-2 and therefore not controlled for multiplicity. Therefore, no conclusions can be drawn.1<\/sup><\/p>\n\n\n\n

          <\/div>\n\n\n\n

          Mean peak FEV1<\/sub> change from baseline at Day 1, Week 6, Week 12, and Week 241,3,4,8<\/sup><\/strong><\/h3><\/div>\n\n\n\n
          <\/div>\n\n\n\n
          \n
          <\/div>\n\n\n\n
          Key Secondary Endpoint Graph_Mobile (1)<\/title>The first graph is labeled, \u201cPeak FEV1: ENHANCE-1\u201d written in white text on a navy blue background. The vertical y-axis of the graph is labeled, \u201cLS Mean Change From Baseline FEV1 (mL).\u201d The y-axis numbers begin at 0 from the bottom of the graph and end at 300 at the top of the graph, counting up from 0 in increments of fifty, from 0, 50, 100, 150, 200, 250, to 300. The horizontal x-axis is labeled \u201cTime\u201d and the numerical markers of the x-axis has markers from Day 1, Week 6, Week 12 (p<0.0001) and Week 24. To the right-hand side of the graph title is a color label. Solid gray colored circle markers indicate Placebo, and light blue colored squares indicate OHTUVAYRE.\n\nThe markers for Day 1, Week 6, Week 12, and Week 24 are marked on a line graph. The placebo markers in dark gray circles are illustrated as circular dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 50 and 100 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. The OHTUVAYRE markers in light blue squares are illustrated as square dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 200 and 250 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. \n\nIn between the Day 1 placebo marker dot and the Day 1 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c152.\u201d In between the Week 6 placebo marker dot and the Week 6 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the vertical dotted line is the number, \u201c136.\u201d In between the Week 12 placebo marker dot and the Week 12 OHTUVAYRE marker dot is a light purple vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c147b.\u201d In between the Week 24 placebo marker dot and the Week 24 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c116.\u201d\n\n—\n\nThe second graph is labeled, \u201cPeak FEV1: ENHANCE-2\u201d written in white text on a purple background. The vertical y-axis of the graph is labeled, \u201cLS Mean Change From Baseline FEV1 (mL).\u201d The y-axis numbers begin at 0 from the bottom of the graph and ends at 300 at the end top of the graph, counting up from 0 in increments of fifty, from 0, 50, 100, 150, 200, 250, to 300. The horizontal x-axis is labeled \u201cTime\u201d and the numerical markers on the x-axis are labeled from Day 1, Week 6, Week 12 (p<0.0001) and Week 24. To the right-hand side of the graph title is a color label. Solid gray colored circle markers indicate Placebo, and light blue colored squares indicate OHTUVAYRE.\n\nThe markers for Day 1, Week 6, Week 12, and Week 24 are marked on a line graph. The placebo markers in dark gray circles are illustrated as circular dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 50 and 100 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. The OHTUVAYRE markers in light blue squares are illustrated as square dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 200 and 250 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. \n\nIn between the Day 1 placebo marker dot and the Day 1 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c157.\u201d In between the Week 6 placebo marker dot and the Week 6 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c152.\u201d In between the Week 12 placebo marker dot and the Week 12 OHTUVAYRE marker dot is a light purple vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the vertical dotted line is the number, \u201c146b.\u201d In between the Week 24 placebo marker dot and the Week 24 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c152.\u201d<\/desc><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/circle><\/path><\/path><\/path><\/path><\/rect><\/path><\/path><\/circle><\/circle><\/circle><\/circle><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/path><\/rect><\/rect><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/circle><\/path><\/path><\/path><\/path><\/rect><\/path><\/circle><\/circle><\/circle><\/circle><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/path><\/rect><\/rect><\/rect><\/rect><\/path><\/path><\/svg> <\/div><\/div>
          Key Secondary Endpoint Graph_Mobile (1)<\/title>The first graph is labeled, \u201cPeak FEV1: ENHANCE-1\u201d written in white text on a navy blue background. The vertical y-axis of the graph is labeled, \u201cLS Mean Change From Baseline FEV1 (mL).\u201d The y-axis numbers begin at 0 from the bottom of the graph and end at 300 at the top of the graph, counting up from 0 in increments of fifty, from 0, 50, 100, 150, 200, 250, to 300. The horizontal x-axis is labeled \u201cTime\u201d and the numerical markers of the x-axis has markers from Day 1, Week 6, Week 12 (p<0.0001) and Week 24. To the right-hand side of the graph title is a color label. Solid gray colored circle markers indicate Placebo, and light blue colored squares indicate OHTUVAYRE.\n\nThe markers for Day 1, Week 6, Week 12, and Week 24 are marked on a line graph. The placebo markers in dark gray circles are illustrated as circular dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 50 and 100 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. The OHTUVAYRE markers in light blue squares are illustrated as square dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 200 and 250 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. \n\nIn between the Day 1 placebo marker dot and the Day 1 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c152.\u201d In between the Week 6 placebo marker dot and the Week 6 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the vertical dotted line is the number, \u201c136.\u201d In between the Week 12 placebo marker dot and the Week 12 OHTUVAYRE marker dot is a light purple vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c147b.\u201d In between the Week 24 placebo marker dot and the Week 24 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c116.\u201d\n\n—\n\nThe second graph is labeled, \u201cPeak FEV1: ENHANCE-2\u201d written in white text on a purple background. The vertical y-axis of the graph is labeled, \u201cLS Mean Change From Baseline FEV1 (mL).\u201d The y-axis numbers begin at 0 from the bottom of the graph and ends at 300 at the end top of the graph, counting up from 0 in increments of fifty, from 0, 50, 100, 150, 200, 250, to 300. The horizontal x-axis is labeled \u201cTime\u201d and the numerical markers on the x-axis are labeled from Day 1, Week 6, Week 12 (p<0.0001) and Week 24. To the right-hand side of the graph title is a color label. Solid gray colored circle markers indicate Placebo, and light blue colored squares indicate OHTUVAYRE.\n\nThe markers for Day 1, Week 6, Week 12, and Week 24 are marked on a line graph. The placebo markers in dark gray circles are illustrated as circular dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 50 and 100 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. The OHTUVAYRE markers in light blue squares are illustrated as square dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 200 and 250 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. \n\nIn between the Day 1 placebo marker dot and the Day 1 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c157.\u201d In between the Week 6 placebo marker dot and the Week 6 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c152.\u201d In between the Week 12 placebo marker dot and the Week 12 OHTUVAYRE marker dot is a light purple vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the vertical dotted line is the number, \u201c146b.\u201d In between the Week 24 placebo marker dot and the Week 24 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c152.\u201d<\/desc><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/circle><\/path><\/path><\/path><\/path><\/rect><\/path><\/path><\/circle><\/circle><\/circle><\/circle><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/path><\/rect><\/rect><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/circle><\/path><\/path><\/path><\/path><\/rect><\/path><\/circle><\/circle><\/circle><\/circle><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/path><\/rect><\/rect><\/rect><\/rect><\/path><\/path><\/svg> <\/div><\/div>
          Key Secondary Endpoint Graph_Mobile (1)<\/title>The first graph is labeled, \u201cPeak FEV1: ENHANCE-1\u201d written in white text on a navy blue background. The vertical y-axis of the graph is labeled, \u201cLS Mean Change From Baseline FEV1 (mL).\u201d The y-axis numbers begin at 0 from the bottom of the graph and end at 300 at the top of the graph, counting up from 0 in increments of fifty, from 0, 50, 100, 150, 200, 250, to 300. The horizontal x-axis is labeled \u201cTime\u201d and the numerical markers of the x-axis has markers from Day 1, Week 6, Week 12 (p<0.0001) and Week 24. To the right-hand side of the graph title is a color label. Solid gray colored circle markers indicate Placebo, and light blue colored squares indicate OHTUVAYRE.\n\nThe markers for Day 1, Week 6, Week 12, and Week 24 are marked on a line graph. The placebo markers in dark gray circles are illustrated as circular dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 50 and 100 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. The OHTUVAYRE markers in light blue squares are illustrated as square dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 200 and 250 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. \n\nIn between the Day 1 placebo marker dot and the Day 1 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c152.\u201d In between the Week 6 placebo marker dot and the Week 6 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the vertical dotted line is the number, \u201c136.\u201d In between the Week 12 placebo marker dot and the Week 12 OHTUVAYRE marker dot is a light purple vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c147b.\u201d In between the Week 24 placebo marker dot and the Week 24 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c116.\u201d\n\n—\n\nThe second graph is labeled, \u201cPeak FEV1: ENHANCE-2\u201d written in white text on a purple background. The vertical y-axis of the graph is labeled, \u201cLS Mean Change From Baseline FEV1 (mL).\u201d The y-axis numbers begin at 0 from the bottom of the graph and ends at 300 at the end top of the graph, counting up from 0 in increments of fifty, from 0, 50, 100, 150, 200, 250, to 300. The horizontal x-axis is labeled \u201cTime\u201d and the numerical markers on the x-axis are labeled from Day 1, Week 6, Week 12 (p<0.0001) and Week 24. To the right-hand side of the graph title is a color label. Solid gray colored circle markers indicate Placebo, and light blue colored squares indicate OHTUVAYRE.\n\nThe markers for Day 1, Week 6, Week 12, and Week 24 are marked on a line graph. The placebo markers in dark gray circles are illustrated as circular dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 50 and 100 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. The OHTUVAYRE markers in light blue squares are illustrated as square dots placed along Day 1, Week 6, Week 12, and Week 24 on a plain white background between the 200 and 250 markers of the y-axis, with a slight downward trend of the line graph as it spans from Day 1 to Week 24. \n\nIn between the Day 1 placebo marker dot and the Day 1 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c157.\u201d In between the Week 6 placebo marker dot and the Week 6 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c152.\u201d In between the Week 12 placebo marker dot and the Week 12 OHTUVAYRE marker dot is a light purple vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the vertical dotted line is the number, \u201c146b.\u201d In between the Week 24 placebo marker dot and the Week 24 OHTUVAYRE marker dot is a light gray vertical dotted line with a downward facing arrow at the bottom and upward facing arrow at the top, and in the middle of the dotted line is the number, \u201c152.\u201d<\/desc><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/circle><\/path><\/path><\/path><\/path><\/rect><\/path><\/path><\/circle><\/circle><\/circle><\/circle><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/path><\/rect><\/rect><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/circle><\/path><\/path><\/path><\/path><\/rect><\/path><\/circle><\/circle><\/circle><\/circle><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/rect><\/path><\/rect><\/rect><\/rect><\/rect><\/path><\/path><\/svg> <\/div><\/div><\/div><\/div>\n\n\n\n
          <\/div>\n<\/div>\n\n\n\n

          Peak FEV1<\/sub> was defined as the highest post-dose FEV1<\/sub> within the first 4 hours after dosing.1<\/sup>
          a<\/sup>One patient was randomized to placebo and treated but was not included in the endpoint analysis due to missing baseline FEV1<\/sub>.3<\/sup><\/p>\n\n\n\n

          <\/div>\n\n\n\n

          Anzueto A, Barjaktarevic IZ, Siler TM, et al. Ensifentrine, a novel phosphodiesterase 3 and 4 inhibitor for the treatment of chronic obstructive pulmonary disease: randomized, double-blind, placebo-controlled, multicenter phase III trials (the ENHANCE Trials). Am J Respir Crit Care Med.<\/em> 2023;208(4):406-416 by permission of the American Thoracic Society.<\/p>\n\n\n\n

          <\/div>\n<\/div><\/div><\/div>\n\n\n\n
          \n\n\n\n
          <\/div>\n\n\n\n
          \n

          The St. George\u2019s Respiratory Questionnaire (SGRQ)<\/h2><\/div>\n\n\n\n
          <\/div>\n\n\n\n

          The SGRQ is designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease.7<\/sup><\/p>\n\n\n\n

          <\/div>\n\n\n\n
          \n
            \n
          • During clinical visits, patients had their HRQoL assessed by a physician using the St. George\u2019s Respiratory Questionnaire1<\/sup><\/li>\n<\/ul>\n<\/div>\n\n\n\n
            <\/div>\n\n\n\n
            \n
            \n

            Part 1: One component<\/h3><\/div>\n\n\n\n
            <\/div>\n\n\n\n\n

            Symptoms<\/mark> (frequency and severity)<\/mark><\/h4>
            \n

            Covers the patients’ recollection of their symptoms (eg, cough, sputum production, shortness of breath, and wheezing) over a preceding period that may range from 1 month to 1 year9<\/sup><\/p>\n<\/div><\/div><\/div><\/div>\n<\/div>\n\n\n\n

            \n

            Part 2: Two components<\/h3><\/div>\n\n\n\n
            <\/div>\n\n\n\n

            Activity<\/mark><\/h4>
            \n

            Evaluates activities that cause breathlessness or are limited because of breathlessness9<\/sup><\/p>\n<\/div><\/div><\/div><\/div>\n\n\n\n

            <\/div>\n\n\n\n
            <\/div>\n\n\n\n

            Impact<\/mark><\/h4>
            \n

            Covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease9<\/sup><\/p>\n<\/div><\/div><\/div><\/div>\n<\/div>\n<\/div>\n\n\n\n

            <\/div>\n\n\n\n

            HRQoL, Health-Related Quality of Life.<\/p>\n\n\n\n

            <\/div>\n<\/div><\/div><\/div>\n\n\n\n
            \n\n\n\n
            <\/div>\n\n\n\n
            \n

            SGRQ responder rates in the ENHANCE trials<\/h2><\/div>\n\n\n\n
            <\/div>\n\n\n\n

            Selected key secondary endpoint:<\/strong> OHTUVAYRE SGRQ responder rate vs placeboa,b<\/sup><\/p>\n\n\n\n

            <\/div>\n\n\n\n

            Key secondary endpoint:<\/strong> SGRQ responder rate at Week 24 was included in the statistical testing hierarchy.1,5,6<\/sup><\/p>\n\n\n\n

            \n
              \n
            • As the pre-specified hierarchical testing criteria were not fully met in ENHANCE-2, SGRQ responder proportion at Week 24 was not formally tested for statistical significance.1,6<\/sup><\/li>\n<\/ul>\n<\/div>\n\n\n\n

              Limitations: <\/strong>SGRQ responder rates at Week 6 and Week 12 were not included in the statistical hierarchy for ENHANCE-1 and ENHANCE-2 and therefore not controlled for multiplicity. Therefore, no conclusions can be drawn.1,5,6<\/sup><\/p>\n\n\n\n

              <\/div>\n\n\n\n
              \n
              \n

              ENHANCE-1:<\/strong> The SGRQ responder rate for patients on OHTUVAYRE was 58.2% compared to 45.9% on placebo at Week 24 [Odds Ratio: 1.49; 95% CI: 1.07, 2.07].4<\/sup><\/p>\n\n\n\n

              <\/div>\n<\/div>\n\n\n\n
              \n

              ENHANCE-2:<\/strong> The SGRQ responder rate for patients on OHTUVAYRE was 45.4% compared to 50.3% on placebo at Week 24 [Odds Ratio: 0.92; 95% CI: 0.66, 1.29].3<\/sup><\/p>\n<\/div>\n<\/div>\n\n\n\n

              <\/div>\n\n\n\n

              a<\/sup>Responder rate is defined as the proportion of patients who achieved minimal clinically important difference (MCID).1,3,4<\/sup>
              b<\/sup>MCID for SGRQ is defined as an improvement from baseline of at least 4 units.7<\/sup>
              CI, confidence interval; ENHANCE, E<\/strong>nsifentrine as a N<\/strong>ovel inHA<\/strong>led N<\/strong>ebulized C<\/strong>OPD thE<\/strong>rapy; LS, least-squares; NS, not significant.<\/p>\n\n\n\n

              <\/div>\n<\/div><\/div><\/div>\n\n\n\n
              <\/div>\n\n\n\n
              \n

              SGRQ total score data<\/h2><\/div>\n\n\n\n
              <\/div>\n\n\n\n

              Secondary endpoints: Mean change from baseline in the SGRQ total scores at Week 6, Week 12, and Week 241,3,4,8<\/sup><\/h3><\/div>\n\n\n\n
              <\/div>\n\n\n\n

              Key secondary endpoint:<\/strong> SGRQ total score at Week 24 was included in the statistical testing hierarchy.<\/p><\/div><\/div>\n\n\n\n

              \n
                \n
              • As the pre-specified hierarchical testing criteria were not fully met in ENHANCE-2, SGRQ total score at Week 24 was not formally tested for statistical significance.1<\/sup><\/li>\n<\/ul>\n<\/div>\n\n\n\n

                Limitations:<\/strong> SGRQ total scores at Week 6 and Week 12 were not included in the statistical hierarchy for ENHANCE-1 and ENHANCE-2 and therefore not controlled for multiplicity. Therefore, no conclusions can be drawn.1<\/sup><\/p>\n\n\n

                Graph Secondary Endpoint SGRQ Desk<\/title>This graphic contains two separate bar charts, one for ENHANCE-1 and one for ENHANCE-2. \n\nThe first graphic is a vertical stacked-bar chart titled, \u201cENHANCE-1\u201d on a navy blue background in white text.\nThe format of the graph is bar graphs that run left to right vertically, indicating Week 6, Week 12, and Week 24 on the x-axis. Week 6 and Week 12 are in standard text and Week 24 is in bold text. The y-axis label is \u201cLS Mean Change from Baseline\u201d in navy blue text. The y-axis numbers begin at -7.0 at the bottom and mark upwards in increments of one (-6.0, -5.0, -4.0, -3.0, -2.0, -1.0, and 0) ending at zero. Underneath the graph is a color label. The light blue gradient color indicates OHTUVAYRE (n=474) and the solid gray indicates Placebo (n=281). \nThe first bar on this graph under the \u201cWeek 6\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-6.2\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just beyond the -6.0 mark on the y-axis, illustrating its -6.2 position. \nThe second bar to the right on this graph under the \u201cWeek 6\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-4.0\u201d written in white text on it. This Placebo bar extends from zero to exactly at the -4.0 mark on the y-axis, illustrating its -4.0 position. \nThe third bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-5.7\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just before the -6.0 mark on the y-axis, illustrating its -5.7 position.\nThe fourth bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-2.7\u201d written in white text on it. This Placebo bar extends from zero just before the -3.0 mark on the y-axis, illustrating its -2.7 position. \nThe fifth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark blue gradient colored OHTUVAYRE bar. It has \u201c-6.2\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just beyond the -6.0 mark on the y-axis, illustrating its -6.2 position.\nThe sixth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark gray colored Placebo bar. It has \u201c-3.9\u201d written in white text on it. This Placebo bar extends from zero just before the -4.0 mark on the y-axis, illustrating its -3.9 position. \nIn small navy blue text, \u201cLS mean difference -2.3 (95% CI: -4.3, -0.3; p=0.025)\u201d is written near the sixth bar of the graph but just outside the bar graph area. \n\n—\nThe second graphic is a vertical stacked-bar chart titled, \u201cENHANCE-2\u201d on a purple background in white text.\nThe format of the graph is bar graphs that run left to right vertically, indicating Week 6, Week 12, and Week 24 on the x-axis. The y-axis label is \u201cLS Mean Change from Baseline\u201d in navy blue text. The y-axis numbers begin at -7.0 at the bottom and mark upwards in increments of one (-6.0, -5.0, -4.0, -3.0, -2.0, -1.0, and 0) ending at zero. Underneath the graph is a color label. The light blue gradient color indicates OHTUVAYRE (n=489) and the light gray indicates Placebo (n=286). \nThe first bar on this graph under the \u201cWeek 6\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-3.6\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just beyond the midpoint between the -3.0 and -4.0 marks on the y-axis, illustrating its -3.6 position. \nThe second bar to the right on this graph under the \u201cWeek 6\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-1.9\u201d written in white text on it. This Placebo bar extends from zero to just before the -2.0 mark on the y-axis, illustrating its -1.9 position. \nThe third bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-4.0\u201d written in white text on it. This OHTUVAYRE bar extends from zero to the -4.0 mark on the y-axis, illustrating its -4.0 position. \nThe fourth bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-2.9\u201d written in white text on it. This Placebo bar extends from zero to just before the -3.0 mark on the y-axis, illustrating its -2.9 position. \nThe fifth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark blue gradient colored OHTUVAYRE bar. It has \u201c-4.5\u201d written in white text on it. This OHTUVAYRE bar extends from zero to exactly between -4.0 mark and the -5.0 mark on the y-axis, illustrating its -4.5 position. \nThe sixth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark gray colored Placebo bar. It has \u201c-4.1\u201d written in white text on it. This Placebo bar extends from zero to just beyond the -4.0 mark on the y-axis, illustrating its -4.1 position. \nA text note that reads, \u201cLS mean difference -0.5 (95% CI: -2.7, 1.7; p=NS)\u201d in small navy blue text is written near the sixth bar of the graph but just outside the bar graph area.<\/desc><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/rect><\/path><\/g><\/g><\/g><\/path><\/path><\/path><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/rect><\/path><\/g><\/g><\/path><\/path><\/path><\/rect><\/path><\/rect><\/path><\/rect><\/path><\/rect><\/path><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/rect><\/clipPath><\/rect><\/clipPath><\/rect><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/rect><\/clipPath><\/rect><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/defs><\/svg> <\/div><\/div>
                Graph Secondary Endpoint SGRQ Desk<\/title>This graphic contains two separate bar charts, one for ENHANCE-1 and one for ENHANCE-2. \n\nThe first graphic is a vertical stacked-bar chart titled, \u201cENHANCE-1\u201d on a navy blue background in white text.\nThe format of the graph is bar graphs that run left to right vertically, indicating Week 6, Week 12, and Week 24 on the x-axis. Week 6 and Week 12 are in standard text and Week 24 is in bold text. The y-axis label is \u201cLS Mean Change from Baseline\u201d in navy blue text. The y-axis numbers begin at -7.0 at the bottom and mark upwards in increments of one (-6.0, -5.0, -4.0, -3.0, -2.0, -1.0, and 0) ending at zero. Underneath the graph is a color label. The light blue gradient color indicates OHTUVAYRE (n=474) and the solid gray indicates Placebo (n=281). \nThe first bar on this graph under the \u201cWeek 6\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-6.2\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just beyond the -6.0 mark on the y-axis, illustrating its -6.2 position. \nThe second bar to the right on this graph under the \u201cWeek 6\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-4.0\u201d written in white text on it. This Placebo bar extends from zero to exactly at the -4.0 mark on the y-axis, illustrating its -4.0 position. \nThe third bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-5.7\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just before the -6.0 mark on the y-axis, illustrating its -5.7 position.\nThe fourth bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-2.7\u201d written in white text on it. This Placebo bar extends from zero just before the -3.0 mark on the y-axis, illustrating its -2.7 position. \nThe fifth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark blue gradient colored OHTUVAYRE bar. It has \u201c-6.2\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just beyond the -6.0 mark on the y-axis, illustrating its -6.2 position.\nThe sixth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark gray colored Placebo bar. It has \u201c-3.9\u201d written in white text on it. This Placebo bar extends from zero just before the -4.0 mark on the y-axis, illustrating its -3.9 position. \nIn small navy blue text, \u201cLS mean difference -2.3 (95% CI: -4.3, -0.3; p=0.025)\u201d is written near the sixth bar of the graph but just outside the bar graph area. \n\n—\nThe second graphic is a vertical stacked-bar chart titled, \u201cENHANCE-2\u201d on a purple background in white text.\nThe format of the graph is bar graphs that run left to right vertically, indicating Week 6, Week 12, and Week 24 on the x-axis. The y-axis label is \u201cLS Mean Change from Baseline\u201d in navy blue text. The y-axis numbers begin at -7.0 at the bottom and mark upwards in increments of one (-6.0, -5.0, -4.0, -3.0, -2.0, -1.0, and 0) ending at zero. Underneath the graph is a color label. The light blue gradient color indicates OHTUVAYRE (n=489) and the light gray indicates Placebo (n=286). \nThe first bar on this graph under the \u201cWeek 6\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-3.6\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just beyond the midpoint between the -3.0 and -4.0 marks on the y-axis, illustrating its -3.6 position. \nThe second bar to the right on this graph under the \u201cWeek 6\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-1.9\u201d written in white text on it. This Placebo bar extends from zero to just before the -2.0 mark on the y-axis, illustrating its -1.9 position. \nThe third bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-4.0\u201d written in white text on it. This OHTUVAYRE bar extends from zero to the -4.0 mark on the y-axis, illustrating its -4.0 position. \nThe fourth bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-2.9\u201d written in white text on it. This Placebo bar extends from zero to just before the -3.0 mark on the y-axis, illustrating its -2.9 position. \nThe fifth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark blue gradient colored OHTUVAYRE bar. It has \u201c-4.5\u201d written in white text on it. This OHTUVAYRE bar extends from zero to exactly between -4.0 mark and the -5.0 mark on the y-axis, illustrating its -4.5 position. \nThe sixth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark gray colored Placebo bar. It has \u201c-4.1\u201d written in white text on it. This Placebo bar extends from zero to just beyond the -4.0 mark on the y-axis, illustrating its -4.1 position. \nA text note that reads, \u201cLS mean difference -0.5 (95% CI: -2.7, 1.7; p=NS)\u201d in small navy blue text is written near the sixth bar of the graph but just outside the bar graph area.<\/desc><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/rect><\/path><\/g><\/g><\/g><\/path><\/path><\/path><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/rect><\/path><\/g><\/g><\/path><\/path><\/path><\/rect><\/path><\/rect><\/path><\/rect><\/path><\/rect><\/path><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/rect><\/clipPath><\/rect><\/clipPath><\/rect><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/rect><\/clipPath><\/rect><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/defs><\/svg> <\/div><\/div>
                Graph Secondary Endpoint SGRQ Mob<\/title>This graphic contains two separate bar charts, one for ENHANCE-1 and one for ENHANCE-2. \n\nThe first graphic is a vertical stacked-bar chart titled, \u201cENHANCE-1\u201d on a navy blue background in white text.\nThe format of the graph is bar graphs that run left to right vertically, indicating Week 6, Week 12, and Week 24 on the x-axis. Week 6 and Week 12 are in standard text and Week 24 is in bold text. The y-axis label is \u201cLS Mean Change from Baseline\u201d in navy blue text. The y-axis numbers begin at -7.0 at the bottom and mark upwards in increments of one (-6.0, -5.0, -4.0, -3.0, -2.0, -1.0, and 0) ending at zero. Underneath the graph is a color label. The light blue gradient color indicates OHTUVAYRE (n=474) and the solid gray indicates Placebo (n=281). \nThe first bar on this graph under the \u201cWeek 6\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-6.2\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just beyond the -6.0 mark on the y-axis, illustrating its -6.2 position. \nThe second bar to the right on this graph under the \u201cWeek 6\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-4.0\u201d written in white text on it. This Placebo bar extends from zero to exactly at the -4.0 mark on the y-axis, illustrating its -4.0 position. \nThe third bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-5.7\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just before the -6.0 mark on the y-axis, illustrating its -5.7 position.\nThe fourth bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-2.7\u201d written in white text on it. This Placebo bar extends from zero just before the -3.0 mark on the y-axis, illustrating its -2.7 position. \nThe fifth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark blue gradient colored OHTUVAYRE bar. It has \u201c-6.2\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just beyond the -6.0 mark on the y-axis, illustrating its -6.2 position.\nThe sixth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark gray colored Placebo bar. It has \u201c-3.9\u201d written in white text on it. This Placebo bar extends from zero just before the -4.0 mark on the y-axis, illustrating its -3.9 position. \nIn small navy blue text, \u201cLS mean difference -2.3 (95% CI: -4.3, -0.3; p=0.025)\u201d is written near the sixth bar of the graph but just outside the bar graph area. \n\n—\nThe second graphic is a vertical stacked-bar chart titled, \u201cENHANCE-2\u201d on a purple background in white text.\nThe format of the graph is bar graphs that run left to right vertically, indicating Week 6, Week 12, and Week 24 on the x-axis. The y-axis label is \u201cLS Mean Change from Baseline\u201d in navy blue text. The y-axis numbers begin at -7.0 at the bottom and mark upwards in increments of one (-6.0, -5.0, -4.0, -3.0, -2.0, -1.0, and 0) ending at zero. Underneath the graph is a color label. The light blue gradient color indicates OHTUVAYRE (n=489) and the light gray indicates Placebo (n=286). \nThe first bar on this graph under the \u201cWeek 6\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-3.6\u201d written in white text on it. This OHTUVAYRE bar extends from zero to just beyond the midpoint between the -3.0 and -4.0 marks on the y-axis, illustrating its -3.6 position. \nThe second bar to the right on this graph under the \u201cWeek 6\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-1.9\u201d written in white text on it. This Placebo bar extends from zero to just before the -2.0 mark on the y-axis, illustrating its -1.9 position. \nThe third bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a light blue gradient colored OHTUVAYRE bar. It has \u201c-4.0\u201d written in white text on it. This OHTUVAYRE bar extends from zero to the -4.0 mark on the y-axis, illustrating its -4.0 position. \nThe fourth bar to the right on this graph under the \u201cWeek 12\u201d x-axis marker is a gray colored Placebo bar. It has \u201c-2.9\u201d written in white text on it. This Placebo bar extends from zero to just before the -3.0 mark on the y-axis, illustrating its -2.9 position. \nThe fifth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark blue gradient colored OHTUVAYRE bar. It has \u201c-4.5\u201d written in white text on it. This OHTUVAYRE bar extends from zero to exactly between -4.0 mark and the -5.0 mark on the y-axis, illustrating its -4.5 position. \nThe sixth bar to the right on this graph under the \u201cWeek 24\u201d x-axis marker is a dark gray colored Placebo bar. It has \u201c-4.1\u201d written in white text on it. This Placebo bar extends from zero to just beyond the -4.0 mark on the y-axis, illustrating its -4.1 position. \nA text note that reads, \u201cLS mean difference -0.5 (95% CI: -2.7, 1.7; p=NS)\u201d in small navy blue text is written near the sixth bar of the graph but just outside the bar graph area.<\/desc><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/path><\/rect><\/path><\/rect><\/path><\/path><\/path><\/path><\/path><\/mask><\/path><\/path><\/path><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/mask><\/path><\/path><\/path><\/g><\/rect><\/path><\/g><\/path><\/path><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/path><\/g><\/path><\/path><\/rect><\/path><\/rect><\/path><\/path><\/path><\/path><\/path><\/path><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/stop><\/stop><\/linearGradient><\/rect><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/path><\/clipPath><\/rect><\/clipPath><\/defs><\/svg> <\/div><\/div><\/div>\n\n\n
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                The Transition Dyspnea Index (TDI)10,11<\/sup><\/h2><\/div>\n\n\n\n

                Designed to quantify breathlessness based on activities of daily living, the TDI is an evaluative instrument that measures how dyspnea changes over time relative to the patient\u2019s baseline.<\/p>\n\n\n\n

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                The TDI focuses on the change over time in three components: functional impairment, magnitude of task, and magnitude of effort.<\/strong><\/p>\n\n\n\n

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