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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 2

Conditions: Asthma

Treatments: Drug: MK-1029; Drug: Placebo; Drug: Montelukast 10 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01656395

1029-012

132230 (Registry Identifier)

2012-000643-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 576 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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576 participants in 8 patient groups, including a placebo group

MK-1029 10 mg

Experimental group

Description:

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

Treatment:

Drug: MK-1029

MK-1029 30 mg

Experimental group

Description:

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

Treatment:

Drug: MK-1029

MK-1029 60 mg

Experimental group

Description:

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

Treatment:

Drug: MK-1029

MK-1029 150 mg

Experimental group

Description:

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

Treatment:

Drug: MK-1029

Montelukast 10 mg

Active Comparator group

Description:

Participants will receive Montelukast 10 mg tablets QD for 12 weeks

Treatment:

Drug: Montelukast 10 mg

Placebo

Placebo Comparator group

Description:

Participants will receive Placebo tablets QD for 12 weeks

Treatment:

Drug: Placebo

MK-1029 1 mg or 3 mg

Experimental group

Description:

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.

Treatment:

Drug: MK-1029

Montelukast 10 mg + MK-1029

Experimental group

Description:

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

Treatment:

Drug: Montelukast 10 mg