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

Phase 2

Completed

• Conditions: Asthma
• Interventions: Drug: MK-1029 150 mg; Drug: MK-1029 Matching-image Placebo; Drug: Montelukast 10 mg; Drug: Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation

• Registration Number: NCT02720081
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-22
• Study First Submitted QC: 2016-03-22
• Study First Posted: 2016-03-25
• Study Start: 2016-05-11
• Primary Completion: 2017-08-16
• Study Completion: 2017-09-06
• Results First Submitted: 2018-07-16
• Status Verified: 2018-08
• Results First Submitted QC: 2018-08-24
• Results First Posted: 2018-08-28
• Last Update Submitted: 2018-08-30
• Last Update Posted: 2018-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 142

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MK-1029 Placebo + Montelukast 10 mg	Montelukast 10 mg	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.
MK-1029 150 mg + Montelukast 10 mg	MK-1029 150 mg	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.
MK-1029 150 mg + Montelukast 10 mg	Montelukast 10 mg	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.
MK-1029 150 mg + Montelukast 10 mg	Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation	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.
MK-1029 Placebo + Montelukast 10 mg	MK-1029 Matching-image Placebo	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.
MK-1029 Placebo + Montelukast 10 mg	Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation	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.

Primary Outcome Measures

Name	Time	Method
Average Change From Baseline in Pre-dose FEV1 at Week 4 and Week 6	Before the first dose (Baseline) and at the end of Weeks 4 and 6 of treatment	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.
Baseline Pre-dose Forced Expiratory Volume in One Second (FEV1)	Before the first dose of study investigational product (Baseline)	FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second.

Secondary Outcome Measures

Name	Time	Method
Percentage of Days With Worsening Asthma Average Over Weeks 3 to 6	Up to 4 weeks	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.
Percentage of Participants Who Discontinued Study Drug Due to an AE	Up to 6 weeks	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.
Change From Baseline in Aspartate Aminotransferase (AST) at Week 6	Baseline and 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.
Change From Baseline in Bilirubin at Week 6	Baseline and 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.
Change From Baseline in Eosinophil (Percent [%]) at Week 6	Baseline and 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.
Percentage of Participants Who Experienced an Adverse Event (AE)	Up to 8 weeks	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.
Change From Baseline in Alkaline Phosphatase (ALP) at Week 6	Baseline and 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.
Change From Baseline in Alanine Aminotransferase (ALT) at Week 6	Baseline and 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.
Change From Baseline in Neutrophil (%) at Week 6	Baseline and 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.
Change From Baseline in Platelet Count at Week 6	Baseline and 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.
Change From Baseline in White Blood Cell Count at Week 6	Baseline and 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.
Change From Baseline in Hematocrit (%) at Week 6	Baseline and 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.
Change From Baseline in Systolic Blood Pressure at Week 2	Baseline and 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.
Change From Baseline in Systolic Blood Pressure at Week 4	Baseline and 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.
Change From Baseline in Systolic Blood Pressure at Week 6	Baseline and 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.
Change From Baseline in Diastolic Blood Pressure at Week 2	Baseline and 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.
Change From Baseline in Diastolic Blood Pressure at Week 4	Baseline and 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.
Change From Baseline in Diastolic Blood Pressure at Week 6	Baseline and 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.
Change From Baseline in Heart Rate at Week 2	Baseline and 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.
Change From Baseline in Heart Rate at Week 4	Baseline and 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.
Change From Baseline in Heart Rate at Week 6	Baseline and 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.
Change From Baseline in Respiratory Rate at Week 2	Baseline and 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.
Change From Baseline in Respiratory Rate at Week 4	Baseline and 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.
Change From Baseline in Respiratory Rate at Week 6	Baseline and 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.