Study of MK-1029 in Participants With Persistent Asthma That Cannot Be Controlled With Montelukast (MK-1029-015)

Study Overview
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Brief Summary
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The purpose of this trial is to compare the safety, tolerability, and efficacy of adding MK-1029 to montelukast in adults with persistent asthma that is uncontrolled while receiving montelukast alone. Participants will have a specific genetic marker for clinical efficacy of MK-1029. The primary hypothesis is that when added to montelukast, treatment with MK-1029 is superior to placebo, as demonstrated by an increase in forced expiratory volume in one second (FEV1), measured as the average change from baseline at the end of Week 4 and Week 6 of treatment.

Official Title
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A Phase-II, Randomized, Placebo-Controlled, Parallel-Group Clinical Trial to Study the Efficacy and Safety of MK-1029 in Adult Subjects With Persistent Asthma That is Uncontrolled While Receiving Montelukast.

Conditions
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Asthma

Intervention / Treatment
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* Drug: MK-1029 150 mg
* Drug: MK-1029 Matching-image Placebo
* Drug: Montelukast 10 mg
* Drug: Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms of persistent asthma for at least one year History of asthma treatments including as-needed inhaled short-acting beta-agonists (albuterol/salbutamol); stable doses of inhaled corticosteroids (ICS), combination ICS/long-acting (inhaled) Beta2-adrenergic agonist (LABA) and/or oral asthma controller(s) Must be able to discontinue or taper asthma controlling medications while receiving Montelukast No history of smoking or no smoking for at least 1 year, with a smoking history of no more than 10 pack-years Body Mass Index (BMI) of 15 kg/m^2 to 40 kg/m^2. Females must not be pregnant (negative serum human chorionic gonadotropin test) or breastfeeding and must not plan to become pregnant for the duration of the study, including the post-treatment follow-up period Women and male participants of reproductive potential must agree to use adequate contraception for the duration of the study Exclusion Criteria: Evidence of another active pulmonary disorder such as bronchiectasis or chronic obstructive pulmonary disease (COPD) Unable to perform acceptable, repeatable spirometry History of myocardial infarction, congestive heart failure, or uncontrolled cardiac arrhythmia within 3 months of screening visit Major surgical procedure(s) within 4 weeks of screening visit Blood donation within 2 weeks of screening visit Treatment in an emergency room for asthma (within 4 weeks) or hospitalization for asthma or respiratory condition within 2 months of screening visit Evidence of active sinus disease within 2 weeks of screening visit Upper respiratory infection (viral or bacterial) within 1 month of screening visit History of a psychiatric disorder within 3 months of screening visit History of human immunodeficiency virus (HIV) Unstable disease of the ophthalmologic, neurological, hepatic, renal, connective tissue, genitourinary, gastrointestinal, cardiovascular or hematologic systems History of cancer (except for successfully treated basal and squamous cell carcinomas of the skin) within 5 years of screening visit Uncontrolled hypertension Participation in a clinical trial involving an investigational drug within 4 weeks of screening visit Hypersensitivity or intolerance to inhaled beta-agonists and/or leukotriene inhibitors or any of their ingredients, including lactose and galactose Known sensitivity to or has not had previous exposure to aspirin or non-steroidal anti-inflammatory drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: MK-1029 150 mg + Montelukast 10 mg<br>Participants receive single-blind MK-1029 Matching-image Placebo + open-label Montelukast 10 mg for a 2 to 4 week run-in period while discontinuing or tapering off asthma controller medications. Participants receive double-blind MK-1029 150 mg + Montelukast 10 mg for 6 weeks in the treatment period. Participants can use rescue medication during both periods as needed. | Drug: MK-1029 150 mg<br>* 150 mg tablet administered orally, once a day (QD), at bedtime<br>Drug: Montelukast 10 mg<br>* 10 mg tablet administered orally, QD, at bedtime<br>* Other names: Montelukast sodium;Drug: Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation<br>* 1 or 2 inhalations 4 times a day (QID) as needed (PRN) as a Rescue Medication<br>|
| Placebo Comparator: MK-1029 Placebo + Montelukast 10 mg<br>Participants receive single-blind MK-1029 Matching-image Placebo + open-label Montelukast 10 mg for a 2 to 4 week run-in period while discontinuing or tapering off asthma controller medications. Participants receive double-blind MK-1029 Matching-image Placebo + Montelukast 10 mg for 6 weeks in the treatment period. Participants can use rescue medication during both periods as needed. | Drug: MK-1029 Matching-image Placebo<br>* Matching-image placebo tablet administered orally, QD, at bedtime<br>Drug: Montelukast 10 mg<br>* 10 mg tablet administered orally, QD, at bedtime<br>* Other names: Montelukast sodium;Drug: Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation<br>* 1 or 2 inhalations 4 times a day (QID) as needed (PRN) as a Rescue Medication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Pre-dose Forced Expiratory Volume in One Second (FEV1) | FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. | Before the first dose of study investigational product (Baseline) | 
| Average Change From Baseline in Pre-dose FEV1 at Week 4 and Week 6 | FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. Data presented represents the average change from baseline at Week 4 and Week 6. | Before the first dose (Baseline) and at the end of Weeks 4 and 6 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Days With Worsening Asthma Average Over Weeks 3 to 6 | A day with worsening asthma was defined as any day during which any of the following occurred: a decrease from baseline in morning (AM) peak expiratory flow (PEF) of more than 20%; AM PEF less than 180 liters/minute (L/min); an increase in β-agonist use of more than 70% (and a minimum increase of at least 2 puffs); an increase from baseline in daytime asthma symptom score of more than 50%; overnight asthma symptom of: Awake all night; an asthma attack, as defined by any day when one or more of the following events due to asthma has occurred: corticosteroid use (systemic); unscheduled visit to the doctor or urgent care clinic; unscheduled visit to the emergency department; and/or hospitalization. Participants needed at least 80% of days with a complete diary during Weeks 3 to 6. A diary is considered complete if none of the above 6 components used to determine asthma worsening are missing. | Up to 4 weeks | 
| Percentage of Participants Who Experienced an Adverse Event (AE) | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to 8 weeks | 
| Percentage of Participants Who Discontinued Study Drug Due to an AE | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to 6 weeks | 
| Change From Baseline in Alkaline Phosphatase (ALP) at Week 6 | Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Alanine Aminotransferase (ALT) at Week 6 | Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Aspartate Aminotransferase (AST) at Week 6 | Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Bilirubin at Week 6 | Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Eosinophil (Percent [%]) at Week 6 | Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Neutrophil (%) at Week 6 | Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Platelet Count at Week 6 | Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in White Blood Cell Count at Week 6 | Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Hematocrit (%) at Week 6 | Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Systolic Blood Pressure at Week 2 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 2 | 
| Change From Baseline in Systolic Blood Pressure at Week 4 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 4 | 
| Change From Baseline in Systolic Blood Pressure at Week 6 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Diastolic Blood Pressure at Week 2 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 2 | 
| Change From Baseline in Diastolic Blood Pressure at Week 4 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 4 | 
| Change From Baseline in Diastolic Blood Pressure at Week 6 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Heart Rate at Week 2 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 2 | 
| Change From Baseline in Heart Rate at Week 4 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 4 | 
| Change From Baseline in Heart Rate at Week 6 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 | 
| Change From Baseline in Respiratory Rate at Week 2 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 2 | 
| Change From Baseline in Respiratory Rate at Week 4 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 4 | 
| Change From Baseline in Respiratory Rate at Week 6 | Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline. | Baseline and Week 6 |