A Dose-Ranging Study of MK-1029 in Adults With Persistent Asthma (MK-1029-012)

NCT01656395 | Terminated Phase 2 Results

• 3 other identifiers: 1029-0122012-000643-27132230
• Study Type: interventional
• Target: 576
• Locations: 0 countries
• Sites: N/A

Brief Summary

This adaptive design, dose-ranging study of MK-1029 will assess the dose-related efficacy and safety of MK-1029 compared with placebo using measures of lung function (forced expiratory volume in 1 second \[FEV1\]). The primary objectives are (1) To demonstrate that MK-1029, compared with placebo, results in dose-related improvements in FEV1 over the last 6 weeks of the 12-week active-treatment period; and (2) To determine the dose-related safety and tolerability of MK-1029 as monotherapy and as concomitant dosing with montelukast over 12 weeks. The primary hypothesis is: MK-1029 is superior to placebo in a dose-related fashion in the average change from baseline in FEV1 over the last 6 weeks of the 12-week active-treatment period.

Conditions

Asthma

Outcome Measures

Primary Outcomes (3)

• Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)

  FEV1 is the amount of air (in liters) forcibly exhaled in one second. Repeated measurements of FEV1 were collected at visits during the 12 week active treatment period and the average change from baseline in FEV1 over the last 6 weeks of the 12-week-treatment period (visits at Week 6, Week 8, Week 10 and Week 12) was estimated using a constrained longitudinal data analysis (cLDA) model. In the cLDA analysis, baseline was the average FEV1 during the placebo run-in period and the post-baseline value was the average FEV1 over Week 6 to Week 12.

  Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)

• Percentage of Participants Who Experience Adverse Events (AEs)

  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the study drug, is also an AE.

  Up to 14 weeks

• Percentage of Participants Who Discontinue Study Due to AEs

  An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the study drug, is also an AE.

  Up to 14 weeks

Secondary Outcomes (10)

• Percentage of Asthma Exacerbation Days

  Week 6 to Week 12

• Average Change From Baseline in Daytime Symptom Score (DSS)

  Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)

• Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs)

  Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)

• Average Change From Baseline in Number of Nocturnal Awakenings

  Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)

• Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF)

  Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)

Study Arms (8)

MK-1029 10 mg

EXPERIMENTAL

Participants receive MK-1029 10 mg tablets once daily (QD) for 12 weeks

Drug: MK-1029

MK-1029 30 mg

EXPERIMENTAL

Participants receive MK-1029 30 mg tablets QD for 12 weeks

Drug: MK-1029

MK-1029 60 mg

EXPERIMENTAL

Participants will receive MK-1029 two 30 mg tablets QD for 12 weeks

Drug: MK-1029

MK-1029 150 mg

EXPERIMENTAL

Participants will receive MK-1029 150 mg tablets QD for 12 weeks

Drug: MK-1029

Montelukast 10 mg

ACTIVE COMPARATOR

Participants will receive Montelukast 10 mg tablets QD for 12 weeks

Drug: Montelukast 10 mg

Placebo

PLACEBO COMPARATOR

Participants will receive Placebo tablets QD for 12 weeks

Drug: Placebo

MK-1029 1 mg or 3 mg

EXPERIMENTAL

Participants will receive either MK-1029 1 mg or 3 mg tablets (dose to be determined based on results of interim analysis from Part I) QD.

Drug: MK-1029

Montelukast 10 mg + MK-1029

EXPERIMENTAL

Participants will receive Montelukast 10 mg tablets QD and MK-1029 tablets (dose to be determined based on results of interim analysis from Part I) QD

Drug: Montelukast 10 mg

Interventions

MK-1029 DRUG

MK-1029 10 mg, 30 mg or 150 mg oral tablets taken QD at bedtime, based on randomization.

MK-1029 1 mg or 3 mg; MK-1029 10 mg; MK-1029 150 mg; MK-1029 30 mg; MK-1029 60 mg

Montelukast 10 mg DRUG

Parts I-II: Participants will receive Montelukast 10 mg tablets QD

Also known as: SINGULAIR®

Montelukast 10 mg; Montelukast 10 mg + MK-1029

Placebo DRUG

Parts I-II: Participants will receive Placebo tablets QD

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• not pregnant or breastfeeding, and not planning to become pregnant during the study
• history of symptoms of persistent asthma for at least one year
• current use of acceptable asthma treatments and willingness to taper or discontinue these treatments; acceptable asthma treatments:
• use of inhaled SABAs (e.g., albuterol/salbutamol) only "as-needed" with no use of asthma controller medications; OR
• use of stable doses of low- or medium-dose inhaled corticosteroids (ICS), alone, or in combination with either a long-acting beta-agonist (LABA) or other asthma controller medications (including leukotriene receptor antagonists) and can tolerate tapering or discontinuation
• no history of smoking OR no smoking within \<1 year with a smoking history of ≤10 pack-years
• ability to maintain a constant day/night, awake/sleep cycle
• agreement to not change habitual consumption of beverages or food containing caffeine throughout the study
• Body Mass Index (BMI) of 15 to 40 kg/m\^2

You may not qualify if:

• myocardial infarction, congestive heart failure, or uncontrolled cardiac arrhythmia within past ≤3 months
• hospitalization within past ≤4 weeks
• major surgical procedure within past ≤4 weeks
• participation in a clinical study involving an investigational drug within past ≤4 weeks
• current regular use or recent (within past ≤5 years) past abuse of alcohol (\>14 drinks/week) or illicit drugs
• donation of a unit of blood within past ≤2 weeks or intention to donate a unit of blood during the study
• evidence of another clinically significant, active pulmonary disorder such as chronic obstructive pulmonary disease (COPD)
• emergency room treatment for asthma within past ≤4 weeks or hospitalization for asthma within past ≤8 weeks
• respiratory tract infection requiring antibiotic treatment within past ≤8 weeks
• evidence of active, clinically significant sinus disease within past ≤1 week
• history of a clinically significant psychiatric disorder, other than stable depression, within past ≤12 weeks
• history of HIV
• hypersensitivity or intolerance to inhaled beta-agonists, leukotriene antagonists, leukotriene synthesis inhibitors, or any of their ingredients, including lactose and galactose
• clinically unstable disease of the ophthalmologic, neurological, hepatic, renal, connective tissue, genitourinary, gastrointestinal, cardiovascular or hematologic systems
• current cancer or history (within past ≤5 years) of cancer (except for successfully treated basal and squamous cell carcinomas of the skin); if cancer-free for \>5 years, study participation may be allowed

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Asthma

Interventions

montelukast

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2012
• First Posted: August 3, 2012
• Study Start: August 23, 2012
• Primary Completion: June 10, 2014
• Study Completion: July 8, 2014
• Last Updated: September 13, 2018
• Results First Posted: September 13, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share