Clinical trial NCT01656395: A Dose-Ranging Study of MK-1029 in Adults With Persistent Asthma (MK-1029-012)
Official title: A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Parallel-Group, Adaptive-Design, Dose-Ranging Study of MK-1029 in Adult Subjects With Persistent Asthma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Asthma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-08-03
Enrollment: 576
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* evidence of uncontrolled hypertension

Primary outcomes:
measure: Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
measure: Percentage of Participants Who Experience Adverse Events (AEs)
timeFrame: Up to 14 weeks
measure: Percentage of Participants Who Discontinue Study Due to AEs
timeFrame: Up to 14 weeks
Secondary outcomes:
measure: Percentage of Asthma Exacerbation Days
timeFrame: Week 6 to Week 12
measure: Average Change From Baseline in Daytime Symptom Score (DSS)
timeFrame: Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
measure: Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs)
timeFrame: Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
measure: Average Change From Baseline in Number of Nocturnal Awakenings
timeFrame: Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
measure: Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF)
timeFrame: Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
measure: Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores
timeFrame: Baseline and Week 12
measure: Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores
timeFrame: Baseline and Week 12
measure: Change From Baseline in Asthma Control Questionnaire (ACQ) Score
timeFrame: Baseline and Week 12
measure: Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score
timeFrame: Baseline and Week 12
measure: Percentage of Asthma Attack Days
timeFrame: Week 6 to Week 12
Other outcomes:
Locations:
Study officials:
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