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

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.

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 Overview

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

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-1029 150 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.	Drug: MK-1029 150 mg; 150 mg tablet administered orally, once a day (QD), at bedtime; Drug: Montelukast 10 mg; 10 mg tablet administered orally, QD, at bedtime; Other Names: SINGULAIR®; Montelukast sodium; Drug: Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation; 1 or 2 inhalations 4 times a day (QID) as needed (PRN) as a Rescue Medication
Placebo Comparator: MK-1029 Placebo + 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.	Drug: Montelukast 10 mg; 10 mg tablet administered orally, QD, at bedtime; Other Names: SINGULAIR®; Montelukast sodium; Drug: Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation; 1 or 2 inhalations 4 times a day (QID) as needed (PRN) as a Rescue Medication; Drug: MK-1029 Matching-image Placebo; Matching-image placebo tablet administered orally, QD, at bedtime

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2016
• Primary Completion (Actual): August 16, 2017
• Study Completion (Actual): September 6, 2017

Study Registration Dates

• First Submitted: March 22, 2016
• First Submitted That Met QC Criteria: March 22, 2016
• First Posted (Estimate): March 25, 2016

Study Record Updates

• Last Update Posted (Actual): September 27, 2018
• Last Update Submitted That Met QC Criteria: August 30, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Montelukast; Albuterol
• Other Study ID Numbers: 1029-015; 2015-005054-36 (EudraCT Number); MK-1029-015 (Other Identifier: Merck Registration Number); 163313 (Registry Identifier: JAPIC-CTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf