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

Asthma Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02720081
• Other study ID #: 1029-015
• Secondary ID: 2015-005054-36MK
• Status: Completed
• Phase: Phase 2
• Start date: May 11, 2016
• Est. completion date: September 6, 2017

Study information

• Verified date: August 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 142
• Est. completion date: September 6, 2017
• Est. primary completion date: August 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• MK-1029 150 mg
150 mg tablet administered orally, once a day (QD), at bedtime
• MK-1029 Matching-image Placebo
Matching-image placebo tablet administered orally, QD, at bedtime
• Montelukast 10 mg
10 mg tablet administered orally, QD, at bedtime
• Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation
1 or 2 inhalations 4 times a day (QID) as needed (PRN) as a Rescue Medication

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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 ß-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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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