{"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":"2026-09-29T10:02:46","modified_gmt":"2026-09-29T10:02:46","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<\/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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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>
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>
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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