A Serious Asthma Outcome Study With Mometasone Furoate/Formoterol Versus Mometasone Furoate in Asthmatics 12 Years and Over (P06241)

Study Overview
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Brief Summary
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The purpose of this study is to test the safety of DULERA. DULERA is a pressurized metered-dose inhaler (MDI) that contains two drugs combined, namely mometasone and formoterol in a single inhaler. Mometasone is an inhaled corticosteroid (ICS), which reduces the inflammation in the airways. Formoterol is a long-acting beta 2 agonist (LABA), which helps to relax the muscles of the airways in the lungs, making it easier to breathe. In combination, mometasone and formoterol are used for the treatment of asthma. This study will evaluate whether participants taking a LABA in combination with an ICS in a single inhaler have a different risk of having serious asthma events (hospitalization, intubation and death) compared to participants taking an ICS alone. The primary safety hypothesis is that the time-to-first serious asthma outcome (SAO) with mometasone furoate/formoterol (MF/F) MDI twice daily (BID) is non-inferior to that with mometasone furoate (MF) MDI BID in adolescents and adults with persistent asthma. If non-inferiority is achieved, the key secondary safety hypothesis of superiority of MF/F over MF will be assessed.

Detailed Description
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Amendments 2 and 3 are specific to Brazil; all other countries will enroll patients under Amendment 1.

Official Title
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A 26-Week Randomized, Double-Blinded, Active Controlled Study Comparing the Safety of Mometasone Furoate/Formoterol Fumarate MDI Fixed Dose Combination Versus Mometasone Furoate MDI Monotherapy in Adolescents and Adults With Persistent Asthma (Protocol No. P06241 Also Known as P202)

Conditions
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Asthma

Intervention / Treatment
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* Drug: Mometasone Furoate/Formoterol MDI 100/5 mcg
* Drug: Mometasone Furoate/Formoterol MDI 200/5 mcg
* Drug: Mometasone Furoate MDI 100 mcg
* Drug: Mometasone Furoate MDI 200 mcg
* Drug: Albuterol 90 mcg /salbutamol 100 mcg HFA MDI
* Drug: Prednisone/prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Persistent asthma for at least 1-year Must use a daily asthma controller medication for at least 4 weeks prior to randomization, including an inhaled corticosteroid (ICS) with or without a long-acting beta agonist (LABA) or other adjunctive asthma therapy OR be using a leukotriene receptor antagonist (LTRA), xanthine or short acting beta agonist (SABA) as a monotherapy. Must be able to discontinue current asthma medication Must have a history of at least one asthma exacerbation in previous 4 to 52 weeks Exclusion Criteria: Unstable asthma Taking high dose ICS with or without other adjunctive therapy who have an Asthma Control Questionnaire 6 (ACQ6) total score ≥ 1.5 Taking LTRA, xanthine or SABA monotherapy with an ACQ-6 total score < 1.5 (controlled) Chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), or other significant, non-asthmatic, lung disease Clinically significant abnormality, illness or disorder of any body or organ system Significant underlying cardiovascular condition which may contraindicate use of a beta-agonist. History of smoking greater than 10-pack years Had an asthma exacerbation within 4 weeks of the Baseline Visit Had more than 4 asthma exacerbations or 2 hospitalizations within 52 weeks of the randomization visit Known or suspected hypersensitivity or intolerance to corticosteroids, beta-2 agonists, or any of the (inactive ingredients) excipients present in the medications used in this study Require the use of chronic systemic steroids, omalizumab, or other monoclonal or polyclonal antibodies Requires the use of beta-blockers History of life-threatening asthma, including an asthma episode that required intubation and/or was associated with hypercapnia requiring noninvasive ventilatory support Lactating, pregnant, or plans to become pregnant during the course of the trial

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mometasone Furoate/Formoterol MDI BID<br>MF/F MDI BID (pooled MF/F MDI 200/10 mcg BID and MF/F MDI 400/10 mcg BID treatments) | Drug: Mometasone Furoate/Formoterol MDI 100/5 mcg<br>* two inhalations BID<br>* Other names: MK-0887A; Dulera/Zenhale;Drug: Mometasone Furoate/Formoterol MDI 200/5 mcg<br>* two inhalations BID<br>* Other names: MK-0887A; Dulera/Zenhale;Drug: Albuterol 90 mcg /salbutamol 100 mcg HFA MDI<br>* use as needed for asthma symptoms<br>Drug: Prednisone/prednisolone<br>* Oral prednisone/prednisolone used only as an emergency rescue medication at the discretion of the investigator<br>|
| Active Comparator: Mometasone Furoate MDI BID<br>MF MDI BID (pooled from MF MDI 200 mcg BID and MF MDI 400 mcg BID treatments) | Drug: Mometasone Furoate MDI 100 mcg<br>* two inhalations BID<br>* Other names: Asmanex;Drug: Mometasone Furoate MDI 200 mcg<br>* two inhalations BID<br>* Other names: Asmanex;Drug: Albuterol 90 mcg /salbutamol 100 mcg HFA MDI<br>* use as needed for asthma symptoms<br>Drug: Prednisone/prednisolone<br>* Oral prednisone/prednisolone used only as an emergency rescue medication at the discretion of the investigator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-First Serious Asthma Outcomes (SAO): Number of First SAO in the MF/F vs MF Arms | The primary safety outcome was the time-to-first SAO (a composite endpoint of adjudicated asthma-related hospitalizations, adjudicated asthma-related intubations, and adjudicated asthma-related deaths). To accomplish this, the number of participants experiencing a first SAO was collected for 26 weeks following initiation of study treatment (or 7 days after the last treatment dose, whichever occurred later). Data generated by this methodology were used to compute a hazard ratio (HR) and 95% confidence interval (CI), modeling the likelihood of a first SAO occurring at any given time in the MF/F arm relative to the MF arm. Although data were sufficient to generate a HR and 95% CI, time-to-first SAO in the overall population could not be accurately reported due to insufficient SAO occurrence. Therefore, the number of first SAO in either arm is reported as a descriptive measure. For each participant, first SAO denotes first event per participant. | 26 weeks, or 7 days after the last treatment dose, whichever occurred later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-First Severe Asthma Exacerbation (SAEX): Number of First SAEX in the MF/F vs MF Arms | The key secondary efficacy outcome was time-to-first protocol-defined asthma exacerbation (SAEX). The SAEX were deteriorations of asthma requiring: use of systemic corticosteroids (tablets, suspension, or injection) for >= 3 consecutive days, in-patient hospitalization >= 24 hours, or an emergency department (ED) visit < 24 hours that required systemic corticosteroids in the MF/F MDI BID arm versus the MF MDI BID arm. The number of first SAEX occurred from initiation of study treatment to 7 days after the last treatment (modified intention-to-treat). This outcome was measured as the HR and 95% CI for the number of first SAEX in the MF/F MDI BID arm versus the number of first SAEX in the MF MDI BID arm. Given insufficient data for SAEX events, it was not informative to report the time-to-first SAEX in the overall population. Therefore, the number of first SAEXs in either arm is reported as a descriptive measure. For each participant, first SAEX denotes first event per participant. | 26 weeks, plus 7 days after the last treatment |