Secondary endpoints

In a clinical study¹ in patients with asthma previously uncontrolled on a medium-dose ICS, the coprimary endpoints were FEV₁ AUC (0-12 hr) and clinically judged deterioration in asthma or reductions in lung function (asthma flare-ups).

Proportion of nights with nocturnal awakenings, change in total rescue medication use, and asthma-specific quality of life were secondary endpoints.

All study medications were administered as 2 inhalations twice daily.

Nocturnal awakenings: 60% reduction with DULERA vs 15% with placebo

In a clinical study in patients with asthma previously uncontrolled on a medium-dose ICS, DULERA demonstrated significant reduction in the proportion of nights with nocturnal awakenings^g vs placebo through 6 months (P<0.001).¹

(g) The proportion of nights with nocturnal awakenings due to asthma requiring rescue medication use (secondary endpoint), where baseline was the proportion of nights with nocturnal awakenings during the week before first treatment dose.

Treatment	Reduction
DULERA 100 mcg/5 mcg (n=186)	Reduction of 60% from baseline (0.18) at endpoint
Placebo (n=194)	Reduction of 15% from baseline (0.15) at endpoint

Rescue medication: Reduced nearly 2 puffs per day with DULERA vs placebo (P<0.001)^1,2

Treatment	Reduction
DULERA 100 mcg/5 mcg (n=186)	Reduction of –0.6 puffs/day from baseline (2.02 puffs/day) at endpoint.
Placebo (n=195)	Increase of 1.1 puffs/day from baseline (1.95 puffs/day) at endpoint.

DULERA is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms.

Asthma-specific quality of life: DULERA demonstrated a clinically meaningful improvement on the subjective impact of asthma on patients’ health-related quality of life as measured by the AQLQ(S)¹

AQLQ(S) results:

A change from baseline ≥0.5 points is considered a clinically meaningful improvement.
The mean difference in AQLQ(S) between patients taking DULERA 100 mcg/5 mcg and placebo was 0.5 points (95% CI: 0.32, 0.68).
Measurement is based on a 7-point scale where 1 = maximum impairment and 7 = no impairment.

Study design

In a 26-week, placebo-controlled study of 781 patients ≥ 12 years of age comparing DULERA 100 mcg/5 mcg (n = 191), mometasone furoate 100 mcg (n = 192), formoterol fumarate 5 mcg (n=202), and placebo (n = 196), each administered as 2 inhalations twice daily by metered-dose inhalation aerosols. All other maintenance therapies were discontinued. This study included a 2- to 3-week run-in period with mometasone furoate 100 mcg, 2 inhalations twice daily. Patients had persistent asthma that was not well controlled on a medium dose of ICS prior to randomization. All treatment groups were balanced with regard to baseline characteristics. This trial included patients ranging from 12 to 76 years of age, 41% male and 59% female, and 72% Caucasian and 28% non-Caucasian. The coprimary endpoints were FEV₁ AUC (0–12 hr) and clinically judged deterioration in asthma or reductions in lung function (asthma flare-ups).¹

Definitions

AQLQ(S) = Asthma Quality of Life Questionnaire (standardized)

AUC = area under the curve

CI = confidence interval

FEV₁ = forced expiratory volume in 1 second

ICS = inhaled corticosteroid

QoL = quality of life

References

1. Nathan RA, Nolte H, Pearlman DS; for P04334 Study Investigators. Twenty-six-week efficacy and safety study of mometasone furoate/formoterol 200/10 μg combination treatment in patients with persistent asthma previously receiving medium-dose inhaled corticosteroids. Allergy Asthma Proc. 2010;31(4):269–279.

2. Data available on request from Merck, Professional Services-DAP, WPI-27, PO Box 4, West Point, PA 19486-0004. Please specify information package US-XFV-00170.

Selected Safety Information

Serious Asthma-Related Events—Hospitalizations, Intubations, and Death

Use of long-acting beta₂-adrenergic agonist (LABA) as monotherapy [without inhaled corticosteroids (ICS)] for asthma is associated with an increased risk of asthma-related death [see Salmeterol Multicenter Asthma Research Trial (SMART) in PI section 5.1]. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy. When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared to ICS alone.

DULERA is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. DULERA is contraindicated in patients with known hypersensitivity to any of the ingredients in DULERA.

DULERA is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms. Increasing use of inhaled, short-acting beta₂-agonists is a marker for deteriorating asthma. In this situation, the patient requires immediate reevaluation with reassessment of the treatment regimen.

Patients using DULERA should not use additional formoterol or other long-acting inhaled beta₂-agonists for any reason.

Oropharyngeal candidiasis may occur. If candidiasis develops, it should be treated with appropriate antifungal therapy, but at times therapy with DULERA may need to be interrupted. Advise patients to rinse the mouth after inhalation.

DULERA should be used with caution in patients with tuberculosis, fungal, bacterial, viral (including chickenpox or measles), or parasitic infections; or ocular herpes simplex infections because of the potential for worsening of these infections. A more serious or even fatal course of chickenpox or measles can occur in susceptible patients.

Particular care is needed for patients who are transferred from systemically active corticosteroids to DULERA. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.

Hypercorticism and adrenal suppression may occur with very high dosages of DULERA or at the regular dosage in susceptible individuals. Patients treated with DULERA should be observed carefully for any evidence of systemic corticosteroid effects. If such changes occur, discontinue DULERA slowly.

Caution should be exercised when considering the coadministration of DULERA with long-term ketoconazole and other known strong CYP3A4 inhibitors, or in patients being treated with MAO inhibitors, tricyclic antidepressants, macrolides, or drugs known to prolong the QTc interval.

There is an elevated risk of arrhythmias in patients receiving concomitant anesthesia with halogenated hydrocarbons.

Discontinue DULERA and institute alternative therapy if paradoxical bronchospasm occurs.

Excessive beta-adrenergic stimulation has been associated with central nervous system and cardiovascular effects. DULERA should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids, including mometasone furoate, a component of DULERA. Patients with major risk factors for decreased BMD should be monitored and treated with established standards of care.

Inhaled corticosteroids, including DULERA, may cause a reduction in growth velocity when administered in pediatric patients.

Glaucoma, increased intraocular pressure, and cataracts have been reported following the use of long-term inhaled corticosteroids, including mometasone furoate, a component of DULERA. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use DULERA long term.

DULERA, like other medications containing sympathomimetic amines, should be used with caution in patients with aneurysm, pheochromocytoma, convulsive disorders, or thyrotoxicosis; and in patients who are unusually responsive to sympathomimetic amines. Doses of the related beta₂-agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.

Be alert to hypokalemia and hyperglycemia as beta₂-agonist medications such as DULERA have the potential to produce adverse cardiovascular effects.

The most common treatment-emergent adverse events reported in ≥3% of patients and more common than placebo included nasopharyngitis, sinusitis, and headache.

Dysphonia was reported in a longer-term treatment trial at an incidence of 5% in patients receiving DULERA 100 mcg/5 mcg and 3.8% in patients receiving DULERA 200 mcg/5 mcg.

Before prescribing DULERA, please read the accompanying Prescribing Information. The Patient Information also is available.

Indication

DULERA is indicated for the twice-daily treatment of asthma in patients 12 years of age and older.

DULERA is NOT indicated for the relief of acute bronchospasm.