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

Phase 2CompletedNCT02720081

Merck Sharp & Dohme LLC142 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

142

Conditions

Asthma

Interventions

MK-1029 150 mg

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Baseline Pre-dose Forced Expiratory Volume in One Second (FEV1)

FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second.

Time frame: 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.

Time frame: Before the first dose (Baseline) and at the end of Weeks 4 and 6 of treatment

Secondary Outcomes

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.

Time frame: 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.

Time frame: Up to 8 weeks

Percentage of Participants Who Discontinued Study Drug Due to an AE

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline and Week 6