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TerminatedNCT01656395Updated Sep 13, 2018Results posted

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

A Phase 2 interventional study of MK-1029 and Montelukast 10 mg in Asthma, sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2018-09-13.

Sponsored by Merck Sharp & Dohme LLC · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
576
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Asthma

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03

In context

Asthma

3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.

This study's enrollment of 576 is above the median of 83 across 2,752 interventional studies indexed under Asthma.

Browse Asthma studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
576 participants (actual)

Study arms

  • Experimental
    MK-1029 10 mg

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

    Drug: MK-1029

  • Experimental
    MK-1029 30 mg

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

    Drug: MK-1029

  • Experimental
    MK-1029 60 mg

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

    Drug: MK-1029

  • Experimental
    MK-1029 150 mg

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

    Drug: MK-1029

  • Active comparator
    Montelukast 10 mg

    Participants will receive Montelukast 10 mg tablets QD for 12 weeks

    Drug: Montelukast 10 mg

  • Placebo comparator
    Placebo

    Participants will receive Placebo tablets QD for 12 weeks

    Drug: Placebo

  • Experimental
    MK-1029 1 mg or 3 mg

    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

  • Experimental
    Montelukast 10 mg + MK-1029

    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

  • DrugMK-1029

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

  • DrugMontelukast 10 mg

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

    Also known as: SINGULAIR®

  • DrugPlacebo

    Parts I-II: Participants will receive Placebo tablets QD

06

What researchers measure

Primary outcomes

  1. 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.

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

  2. 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.

    Time frame: Up to 14 weeks

  3. 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.

    Time frame: Up to 14 weeks

Secondary outcomes

  1. Percentage of Asthma Exacerbation Days

    An asthma exacerbation day was defined as a day with ANY of the following: a decrease from Baseline in morning (AM) Peak Expiratory Flow (PEF) of more than 20%, an AM PEF of less than 180 liters (L)/min, an increase in Short Acting Beta2 Agonist (SABA) 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%, an overnight asthma symptom of: Awake "all night", or an asthma attack. Information on asthma exacerbation days was recorded throughout the study in the participant's electronic diary (e-Diary), and an Analysis of Variance (ANOVA) was used to calculate the average percentage of days with asthma exacerbations over Week 6 to Week 12.

    Time frame: Week 6 to Week 12

  2. Average Change From Baseline in Daytime Symptom Score (DSS)

    The Daytime Symptom Score assessed daytime asthma symptoms. In the evening just before going to bed, participants scored their asthma symptoms for the period since arising by answering the following 4 questions in eDiaries: 1) How often did you experience asthma symptoms today?, 2) How much did your asthma symptoms bother you?, 3) How much activity could you do today? and 4) How often did your asthma affect your activities today? The 4 questions were scored on a 7-point scale (0=best to 6=worst) and averaged for a single score. The average change from baseline in DSS 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 cLDA model. In the cLDA analysis, baseline was the average DSS score during the placebo run-in period and the post-baseline value was the average DSS Score over Week 6 to Week 12.

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

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

    Twice daily (upon arising and before going to sleep), participants recorded the total number of puff (actuations) of SABA used for asthma symptoms in their eDiaries. The number of SABA puffs used in one day was calculated based on eDiary entries as the sum of daytime and nighttime number of puffs of SABA. The average change from baseline over the last 6 weeks of the 12-week-treatment period (visits at Week 6, Week 8, Week 10 and Week 12) in the daily number of SABA puffs was estimated using a cLDA model. In the cLDA analysis, Baseline was the average number of SABA puffs used in one day during the placebo run-in period and the post-baseline value was calculated as the average number of SABA puffs used in one day over Week 6 to Week 12.

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

  4. Average Change From Baseline in Number of Nocturnal Awakenings

    The number of nights per week (between consecutive visits) that a participant awakened with asthma was based on eDiary entries and was calculated by dividing the number of nights a participant awakened with asthma (positive responses of once, more than once, awake "all night") by the total number of nights (all responses) and then multiplying by 7 (standardized to a 7-day period). The average change from baseline in number of nocturnal awakenings 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 cLDA model. In the cLDA analysis, baseline was the average number of nocturnal awakenings during the placebo run-in period and the post-baseline value was calculated as the average number of nocturnal awakenings over Week 6 to Week 12.

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

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

    PEF was defined as a person's maximum speed (rate) of expiration as measured with a peak flow meter in liters per minute. Participants performed triplicate PEF measurements twice daily using a PEF meter, in the AM upon rising and in the PM immediately before study drug administration at bedtime. All three values were recorded and the average of the best morning PEF and the best evening PEF for each day (AM/PM) was determined through the e-Diary. The average change from Baseline in AM/PM PEF over the last 6 weeks of a 12-week treatment period (visits at Week 6, Week 8, Week 10 and Week 12) was estimated using a cLDA model. In the cLDA analysis, baseline was the average AM/PM PEF value during the placebo run-in period and the post-baseline value was calculated as the average AM/PM PEF over Week 6 to Week 12.

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

  6. Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores

    The AQLQ(S) is a 32-item questionnaire with questions on 4 domains (asthma symptoms, activity limitation, emotional function and environmental stimuli) over the previous 2 weeks. Responses were scored on a 7-point scale (1=worst to 7=best). Each domain score is defined as the average score of all answered questions in that domain. The AQLQ(S) Overall Score is defined as the average of all available item scores (1=worst to 7=best). The changes from baseline are presented for the overall scores and the individual domain scores. Baseline was the last measurement taken prior to the first double-blind study drug. The ending values were calculated as the average AQLQ(S) Overall Score and domain scores at Week 12 of a 12-week treatment period. Statistical analyses are provided for the AQLQ(S) Overall Scores only.

    Time frame: Baseline and Week 12

  7. Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores

    The AQLQ(S) is a 32-item questionnaire with questions on 4 domains (asthma symptoms, activity limitation, emotional function and environmental stimuli) over the previous 2 weeks. Responses were scored on a 7-point scale (1=worst to 7=best). Each domain score is defined as the average score of all answered questions in that domain. The AQLQ(S) Overall Score is defined as the average of all available item scores (1=worst to 7=best). The percentage of participants who experienced a ≥0.5 increase in AQLQ(S) Overall and Domain Scores at Week 12 compared to baseline was calculated using the Miettinen and Nurminen (MN) method. Statistical analyses are provide for the AQLQ(S) Overall Score response rate only.

    Time frame: Baseline and Week 12

  8. Change From Baseline in Asthma Control Questionnaire (ACQ) Score

    The ACQ is a validated 6-item measure of asthma control to evaluate asthma control in response to therapy. Participants evaluate their asthma over the previous week by answering 6 questions: How often were you woken by your asthma during the night? How bad were your asthma symptoms when you woke up in the morning? How limited were you in your activities because of your asthma? How much shortness of breath did you experience because of your asthma? How much of the time did you wheeze? How many puffs/inhalations of short-acting bronchodilator have you used each day? Each response to a question was scored on a 7-point scale (0=best to 6=worst). The ACQ score is the average of the scores for the 6 items. Change from baseline to Week 12 in ACQ was estimated using a cLDA model. In the cLDA analysis, the Baseline value was the last measurement taken prior to the first double-blind study drug and the post-baseline value was calculated as the average ACQ Score at Week 12.

    Time frame: Baseline and Week 12

  9. Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score

    The ACQ is a validated 6-item measure of asthma control to evaluate asthma control in response to therapy. Participants evaluate their asthma over the previous week by answering 6 questions: How often were you woken by your asthma during the night? How bad were your asthma symptoms when you woke up in the morning? How limited were you in your activities because of your asthma? How much shortness of breath did you experience because of your asthma? How much of the time did you wheeze? How many puffs/inhalations of short-acting bronchodilator have you used each day? Each response to a question was scored on a 7-point scale (0=best to 6=worst). The ACQ score is the average of the scores for the 6 items. The percentage of participants who experienced a ≥0.5 decrease in ACQ Score at Week 12 compared to Baseline was calculated using the MN method.

    Time frame: Baseline and Week 12

  10. Percentage of Asthma Attack Days

    An asthma attack was defined as asthma symptoms during the previous 24 hours requiring one or more of the following: corticosteroid use (systemic), unscheduled visit to the doctor or urgent care clinic, unscheduled visit to the emergency department or hospitalization. Information on asthma attacks was recorded throughout the study in the participant's e-Diary, and an Analysis of Variance (ANOVA) was used to calculate the average percentage of asthma attack days over Week 6 to Week 12 of a 12-week treatment period.

    Time frame: Week 6 to Week 12

07

Results

Posted Sep 13, 2018

Participant flow

Participant flow — Overall Study
MilestoneMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlaceboMK-1029 1 mg or 3 mgMontelukast 10 mg + MK-1029
Started60127142536013400
Treated participants58126135526012600
Completed439310641469400
Not completed17343612144000
Withdrew: Adverse event114545700
Withdrew: Lack of efficacy18611600
Withdrew: Lost to follow-up10000000
Withdrew: Non-compliance with study drug11001100
Withdrew: Other00100100
Withdrew: Physician decision23323300
Withdrew: Pregnancy00100000
Withdrew: Progressive disease00000100
Withdrew: Protocol violation669241000
Withdrew: Screen failure21710800
Withdrew: Withdrawal by subject31420300

Outcome measures

PrimaryAverage 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.

Time frame:
Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
Reported as:
Least squares mean · Liters
Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
LitersMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)0.065 (-0.009 to 0.139)0.004 (-0.075 to 0.083)0.063 (-0.019 to 0.144)0.036 (-0.04 to 0.112)0.039 (-0.033 to 0.111)0.043 (-0.032 to 0.119)
Statistical analysis
  • MK-1029 10 mg vs Placebo · cLDA model · p = 0.685 · Mean difference (final values): 0.022 · 95% CI -0.084 to 0.127
  • MK-1029 30 mg vs Placebo · cLDA model · p = 0.477 · Mean difference (final values): -0.04 · 95% CI -0.149 to 0.07
  • MK-1029 60 mg vs Placebo · cLDA model · p = 0.733 · Mean difference (final values): 0.019 · 95% CI -0.092 to 0.13
  • MK-1029 150 mg vs Placebo · cLDA model · p = 0.89 · Mean difference (final values): -0.008 · 95% CI -0.115 to 0.1
  • Montelukast 10 mg vs Placebo · cLDA model · p = 0.935 · Mean difference (final values): -0.004 · 95% CI -0.109 to 0.1
PrimaryPercentage 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.

Time frame:
Up to 14 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants Who Experience Adverse Events (AEs)
Percentage of participantsMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Percentage of Participants Who Experience Adverse Events (AEs)44.848.447.453.856.757.9
PrimaryPercentage 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.

Time frame:
Up to 14 weeks
Reported as:
Number · Percentage of participants
Percentage of Participants Who Discontinue Study Due to AEs
Percentage of participantsMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Percentage of Participants Who Discontinue Study Due to AEs1.710.33.77.78.35.6
SecondaryPercentage of Asthma Exacerbation Days

An asthma exacerbation day was defined as a day with ANY of the following: a decrease from Baseline in morning (AM) Peak Expiratory Flow (PEF) of more than 20%, an AM PEF of less than 180 liters (L)/min, an increase in Short Acting Beta2 Agonist (SABA) 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%, an overnight asthma symptom of: Awake "all night", or an asthma attack. Information on asthma exacerbation days was recorded throughout the study in the participant's electronic diary (e-Diary), and an Analysis of Variance (ANOVA) was used to calculate the average percentage of days with asthma exacerbations over Week 6 to Week 12.

Time frame:
Week 6 to Week 12
Reported as:
Least squares mean · Percentage of Asthma Exacerbation Days
Percentage of Asthma Exacerbation Days
Percentage of Asthma Exacerbation DaysMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Percentage of Asthma Exacerbation Days17.704 (10.657 to 24.75)15.812 (8.334 to 23.29)15.435 (7.752 to 23.118)20.238 (13.353 to 27.124)19.657 (12.845 to 26.47)24.904 (17.424 to 32.384)
Statistical analysis
  • MK-1029 10 mg vs Placebo · ANOVA · p = 0.169 · Mean difference (final values): -7.2 · 95% CI -17.48 to 3.08
  • MK-1029 30 mg vs Placebo · ANOVA · p = 0.092 · Mean difference (final values): -9.092 · 95% CI -19.67 to 1.485
  • MK-1029 60 mg vs Placebo · ANOVA · p = 0.083 · Mean difference (final values): -9.469 · 95% CI -20.19 to 1.25
  • MK-1029 150 mg vs Placebo · ANOVA · p = 0.367 · Mean difference (final values): -4.666 · 95% CI -14.83 to 5.501
  • Montelukast 10 mg vs Placebo · ANOVA · p = 0.308 · Mean difference (final values): -5.247 · 95% CI -15.36 to 4.871
SecondaryAverage Change From Baseline in Daytime Symptom Score (DSS)

The Daytime Symptom Score assessed daytime asthma symptoms. In the evening just before going to bed, participants scored their asthma symptoms for the period since arising by answering the following 4 questions in eDiaries: 1) How often did you experience asthma symptoms today?, 2) How much did your asthma symptoms bother you?, 3) How much activity could you do today? and 4) How often did your asthma affect your activities today? The 4 questions were scored on a 7-point scale (0=best to 6=worst) and averaged for a single score. The average change from baseline in DSS 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 cLDA model. In the cLDA analysis, baseline was the average DSS score during the placebo run-in period and the post-baseline value was the average DSS Score over Week 6 to Week 12.

Time frame:
Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
Reported as:
Least squares mean · Score on a scale
Average Change From Baseline in Daytime Symptom Score (DSS)
Score on a scaleMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Average Change From Baseline in Daytime Symptom Score (DSS)-0.398 (-0.612 to -0.184)-0.134 (-0.358 to 0.091)-0.364 (-0.591 to -0.137)-0.120 (-0.325 to 0.086)-0.411 (-0.617 to -0.206)-0.276 (-0.495 to -0.056)
Statistical analysis
  • MK-1029 10 mg vs Placebo · cLDA model · p = 0.429 · Mean difference (final values): -0.122 · 95% CI -0.427 to 0.182
  • MK-1029 30 mg vs Placebo · cLDA model · p = 0.370 · Mean difference (final values): 0.142 · 95% CI -0.169 to 0.454
  • MK-1029 60 mg vs Placebo · cLDA model · p = 0.579 · Mean difference (final values): -0.089 · 95% CI -0.402 to 0.225
  • MK-1029 150 mg vs Placebo · cLDA model · p = 0.305 · Mean difference (final values): 0.156 · 95% CI -0.142 to 0.454
  • Montelukast 10 mg vs Placebo · cLDA model · p = 0.372 · Mean difference (final values): -0.136 · 95% CI -0.434 to 0.163
SecondaryAverage Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs)

Twice daily (upon arising and before going to sleep), participants recorded the total number of puff (actuations) of SABA used for asthma symptoms in their eDiaries. The number of SABA puffs used in one day was calculated based on eDiary entries as the sum of daytime and nighttime number of puffs of SABA. The average change from baseline over the last 6 weeks of the 12-week-treatment period (visits at Week 6, Week 8, Week 10 and Week 12) in the daily number of SABA puffs was estimated using a cLDA model. In the cLDA analysis, Baseline was the average number of SABA puffs used in one day during the placebo run-in period and the post-baseline value was calculated as the average number of SABA puffs used in one day over Week 6 to Week 12.

Time frame:
Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
Reported as:
Least squares mean · Number of SABA Puffs
Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs)
Number of SABA PuffsMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs)-1.373 (-1.847 to -0.899)-0.920 (-1.420 to -0.421)-0.955 (-1.461 to -0.450)-0.571 (-1.031 to -0.111)-1.234 (-1.694 to -0.774)-0.845 (-1.334 to -0.356)
Statistical analysis
  • MK-1029 10 mg vs Placebo · cLDA model · p = 0.114 · Mean difference (final values): -0.528 · 95% CI -1.184 to 0.128
  • MK-1029 30 mg vs Placebo · cLDA model · p = 0.827 · Mean difference (final values): -0.075 · 95% CI -0.75 to 0.6
  • MK-1029 60 mg vs Placebo · cLDA model · p = 0.75 · Mean difference (final values): -0.11 · 95% CI -0.789 to 0.569
  • MK-1029 150 mg vs Placebo · cLDA model · p = 0.403 · Mean difference (final values): 0.275 · 95% CI -0.371 to 0.921
  • Montelukast 10 mg vs Placebo · cLDA model · p = 0.237 · Mean difference (final values): -0.389 · 95% CI -1.035 to 0.257
SecondaryAverage Change From Baseline in Number of Nocturnal Awakenings

The number of nights per week (between consecutive visits) that a participant awakened with asthma was based on eDiary entries and was calculated by dividing the number of nights a participant awakened with asthma (positive responses of once, more than once, awake "all night") by the total number of nights (all responses) and then multiplying by 7 (standardized to a 7-day period). The average change from baseline in number of nocturnal awakenings 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 cLDA model. In the cLDA analysis, baseline was the average number of nocturnal awakenings during the placebo run-in period and the post-baseline value was calculated as the average number of nocturnal awakenings over Week 6 to Week 12.

Time frame:
Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
Reported as:
Least squares mean · Number of awakenings
Average Change From Baseline in Number of Nocturnal Awakenings
Number of awakeningsMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Average Change From Baseline in Number of Nocturnal Awakenings-1.277 (-1.861 to -0.692)-0.900 (-1.518 to -0.282)-1.286 (-1.912 to -0.661)-1.277 (-1.844 to -0.710)-1.107 (-1.674 to -0.540)-1.036 (-1.639 to -0.432)
Statistical analysis
  • MK-1029 10 mg vs Placebo · cLDA model · p = 0.565 · Mean difference (final values): -0.241 · 95% CI -1.066 to 0.583
  • MK-1029 30 mg vs Placebo · cLDA model · p = 0.754 · Mean difference (final values): 0.135 · 95% CI -0.713 to 0.983
  • MK-1029 60 mg vs Placebo · cLDA model · p = 0.563 · Clda model: -0.251 · 95% CI -1.104 to 0.603
  • MK-1029 150 mg vs Placebo · cLDA model · p = 0.559 · Mean difference (final values): -0.241 · 95% CI -1.053 to 0.571
  • Montelukast 10 mg vs Placebo · cLDA model · p = 0.863 · Mean difference (final values): -0.071 · 95% CI -0.883 to 0.741
SecondaryAverage Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF)

PEF was defined as a person's maximum speed (rate) of expiration as measured with a peak flow meter in liters per minute. Participants performed triplicate PEF measurements twice daily using a PEF meter, in the AM upon rising and in the PM immediately before study drug administration at bedtime. All three values were recorded and the average of the best morning PEF and the best evening PEF for each day (AM/PM) was determined through the e-Diary. The average change from Baseline in AM/PM PEF over the last 6 weeks of a 12-week treatment period (visits at Week 6, Week 8, Week 10 and Week 12) was estimated using a cLDA model. In the cLDA analysis, baseline was the average AM/PM PEF value during the placebo run-in period and the post-baseline value was calculated as the average AM/PM PEF over Week 6 to Week 12.

Time frame:
Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12)
Reported as:
Least squares mean · Liters/minutes
Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF)
Liters/minutesMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF)-1.857 (-16.13 to 12.413)3.850 (-11.26 to 18.960)7.174 (-8.124 to 22.472)2.713 (-11.12 to 16.543)-4.005 (-17.83 to 9.825)-2.401 (-17.16 to 12.357)
Statistical analysis
  • MK-1029 10 mg vs Placebo · cLDA model · p = 0.958 · Mean difference (final values): 0.544 · 95% CI -19.92 to 21.007
  • MK-1029 30 mg vs Placebo · cLDA model · p = 0.559 · Mean difference (final values): 6.251 · 95% CI -14.81 to 27.307
  • MK-1029 60 mg vs Placebo · cLDA model · p = 0.374 · Median difference (final values): 9.575 · 95% CI -11.62 to 30.766
  • MK-1029 150 mg vs Placebo · cLDA model · p = 0.618 · Mean difference (final values): 5.114 · 95% CI -15.04 to 25.272
  • Montelukast 10 mg vs Placebo · cLDA model · p = 0.876 · Mean difference (final values): -1.604 · 95% CI -21.76 to 18.554
SecondaryChange From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores

The AQLQ(S) is a 32-item questionnaire with questions on 4 domains (asthma symptoms, activity limitation, emotional function and environmental stimuli) over the previous 2 weeks. Responses were scored on a 7-point scale (1=worst to 7=best). Each domain score is defined as the average score of all answered questions in that domain. The AQLQ(S) Overall Score is defined as the average of all available item scores (1=worst to 7=best). The changes from baseline are presented for the overall scores and the individual domain scores. Baseline was the last measurement taken prior to the first double-blind study drug. The ending values were calculated as the average AQLQ(S) Overall Score and domain scores at Week 12 of a 12-week treatment period. Statistical analyses are provided for the AQLQ(S) Overall Scores only.

Time frame:
Baseline and Week 12
Reported as:
Mean · Score on a scale
Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores
Score on a scaleMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Overall Score0.533 ± 1.0070.256 ± 0.9970.696 ± 1.0400.999 ± 1.2550.736 ± 1.0280.458 ± 1.176
Activity Domain0.46 ± 1.050.27 ± 0.980.62 ± 1.080.96 ± 1.320.66 ± 1.030.44 ± 1.18
Symptoms Domain0.59 ± 1.200.34 ± 1.240.80 ± 1.121.02 ± 1.250.83 ± 1.110.47 ± 1.29
Emotional Function Domain0.55 ± 1.350.06 ± 1.170.75 ± 1.261.12 ± 1.620.70 ± 1.200.45 ± 1.37
Environmental Stimuli Domain0.53 ± 1.190.21 ± 0.900.54 ± 1.200.89 ± 1.470.70 ± 1.180.49 ± 1.43
Statistical analysis
  • MK-1029 10 mg vs Placebo · cLDA model · p = 0.682 · Mean difference (final values): 0.076 · 95% CI -0.288 to 0.440
  • MK-1029 30 mg vs Placebo · cLDA model · p = 0.807 · Mean difference (final values): -0.047 · 95% CI -0.422 to 0.329
  • MK-1029 60 mg vs Placebo · cLDA model · p = 0.403 · Mean difference (final values): 0.165 · 95% CI -0.222 to 0.552
  • MK-1029 150 mg vs Placebo · cLDA model · p = 0.051 · Mean difference (final values): 0.375 · 95% CI -0.001 to 0.751
  • Montelukast 10 mg vs Placebo · cLDA model · p = 0.086 · Mean difference (final values): 0.319 · 95% CI -0.045 to 0.683
SecondaryPercentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores

The AQLQ(S) is a 32-item questionnaire with questions on 4 domains (asthma symptoms, activity limitation, emotional function and environmental stimuli) over the previous 2 weeks. Responses were scored on a 7-point scale (1=worst to 7=best). Each domain score is defined as the average score of all answered questions in that domain. The AQLQ(S) Overall Score is defined as the average of all available item scores (1=worst to 7=best). The percentage of participants who experienced a ≥0.5 increase in AQLQ(S) Overall and Domain Scores at Week 12 compared to baseline was calculated using the Miettinen and Nurminen (MN) method. Statistical analyses are provide for the AQLQ(S) Overall Score response rate only.

Time frame:
Baseline and Week 12
Reported as:
Number · Percentage of participants
Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores
Percentage of participantsMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Overall Score48.9940.4957.2264.4864.0846.14
Activity Domain47.1940.4650.0060.0752.3642.61
Symptoms Domain52.5942.6359.6657.7664.0848.13
Emotional Function Domain56.1931.9562.1057.7653.9149.90
Environmental Stimuli Domain41.7942.6059.6659.9753.1648.13
Statistical analysis
  • MK-1029 10 mg vs Placebo · MN method · p = 0.7687 · Mean difference (final values): 2.8 · 95% CI -16.0 to 21.3
  • MK-1029 30 mg vs Placebo · MN Method · p = 0.4943 · Mean difference (final values): -6.6 · 95% CI -24.9 to 12.2
  • MK-1029 60 mg vs Placebo · MN method · p = 0.3003 · Mean difference (final values): 10.5 · 95% CI -9.4 to 29.6
  • MK-1029 150 mg vs Placebo · MN method · p = 0.0774 · Mean difference (final values): 17.5 · 95% CI -1.9 to 35.7
  • Montelukast 10 mg vs Placebo · MN method · p = 0.0555 · Mean difference (final values): 18.2 · 95% CI -0.4 to 35.5
SecondaryChange From Baseline in Asthma Control Questionnaire (ACQ) Score

The ACQ is a validated 6-item measure of asthma control to evaluate asthma control in response to therapy. Participants evaluate their asthma over the previous week by answering 6 questions: How often were you woken by your asthma during the night? How bad were your asthma symptoms when you woke up in the morning? How limited were you in your activities because of your asthma? How much shortness of breath did you experience because of your asthma? How much of the time did you wheeze? How many puffs/inhalations of short-acting bronchodilator have you used each day? Each response to a question was scored on a 7-point scale (0=best to 6=worst). The ACQ score is the average of the scores for the 6 items. Change from baseline to Week 12 in ACQ was estimated using a cLDA model. In the cLDA analysis, the Baseline value was the last measurement taken prior to the first double-blind study drug and the post-baseline value was calculated as the average ACQ Score at Week 12.

Time frame:
Baseline and Week 12
Reported as:
Least squares mean · Score on a scale
Change From Baseline in Asthma Control Questionnaire (ACQ) Score
Score on a scaleMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Change From Baseline in Asthma Control Questionnaire (ACQ) Score-0.807 (-1.088 to -0.527)-0.736 (-1.033 to -0.438)-0.855 (-1.170 to -0.541)-1.066 (-1.364 to -0.768)-0.931 (-1.215 to -0.648)-0.704 (-0.982 to -0.426)
Statistical analysis
  • MK-1029 10 mg vs Placebo · cLDA model · p = 0.603 · Mean difference (final values): -0.104 · 95% CI -0.495 to 0.288
  • MK-1029 30 mg vs Placebo · cLDA model · p = 0.875 · Mean difference (final values): -0.032 · 95% CI -0.436 to 0.372
  • MK-1029 60 mg vs Placebo · cLDA model · p = 0.476 · Mean difference (final values): -0.151 · 95% CI -0.568 to 0.265
  • MK-1029 150 mg vs Placebo · cLDA model · p = 0.079 · Mean difference (final values): -0.362 · 95% CI -0.767 to 0.042
  • Montelukast 10 mg vs Placebo · cLDA model · p = 0.257 · Mean difference (final values): -0.227 · 95% CI -0.621 to 0.166
SecondaryPercentage of Participants With a ≥0.5 Change From Baseline in ACQ Score

The ACQ is a validated 6-item measure of asthma control to evaluate asthma control in response to therapy. Participants evaluate their asthma over the previous week by answering 6 questions: How often were you woken by your asthma during the night? How bad were your asthma symptoms when you woke up in the morning? How limited were you in your activities because of your asthma? How much shortness of breath did you experience because of your asthma? How much of the time did you wheeze? How many puffs/inhalations of short-acting bronchodilator have you used each day? Each response to a question was scored on a 7-point scale (0=best to 6=worst). The ACQ score is the average of the scores for the 6 items. The percentage of participants who experienced a ≥0.5 decrease in ACQ Score at Week 12 compared to Baseline was calculated using the MN method.

Time frame:
Baseline and Week 12
Reported as:
Number · Percentage of participants
Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score
Percentage of participantsMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score65.5159.5766.6071.1164.7262.43
Statistical analysis
  • MK-1029 10 mg vs Placebo · MN method · p = 0.742 · Mean difference (final values): 3.1 · 95% CI -15.1 to 21.1
  • MK-1029 30 mg vs Placebo · MN method · p = 0.7248 · Mean difference (final values): -3.4 · 95% CI -22.1 to 15.4
  • MK-1029 60 mg vs Placebo · MN method · p = 0.6991 · Mean difference (final values): 3.8 · 95% CI -15.6 to 22.6
  • MK-1029 150 mg vs Placebo · MN method · p = 0.3934 · Mean difference (final values): 8.1 · 95% CI -10.6 to 26.2
  • Montelukast 10 mg vs Placebo · MN method · p = 0.8032 · Mean difference (final values): 2.3 · 95% CI -16.0 to 20.5
SecondaryPercentage of Asthma Attack Days

An asthma attack was defined as asthma symptoms during the previous 24 hours requiring one or more of the following: corticosteroid use (systemic), unscheduled visit to the doctor or urgent care clinic, unscheduled visit to the emergency department or hospitalization. Information on asthma attacks was recorded throughout the study in the participant's e-Diary, and an Analysis of Variance (ANOVA) was used to calculate the average percentage of asthma attack days over Week 6 to Week 12 of a 12-week treatment period.

Time frame:
Week 6 to Week 12
Reported as:
Least squares mean · Percentage
Percentage of Asthma Attack Days
PercentageMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
Percentage of Asthma Attack Days0.482 (-0.159 to 1.122)0.182 (-0.49 to 0.854)0.017 (-0.673 to 0.708)0.637 (0.011 to 1.262)0.248 (-0.364 to 0.86)0.557 (-0.115 to 1.230)
Statistical analysis
  • MK-1029 10 mg vs Placebo · ANOVA · p = 0.873 · Mean difference (final values): -0.075 · 95% CI -1.004 to 0.853
  • MK-1029 30 mg vs Placebo · ANOVA · p = 0.437 · Mean difference (final values): -0.376 · 95% CI -1.326 to 0.575
  • MK-1029 60 mg vs Placebo · ANOVA · p = 0.270 · Mean difference (final values): -0.540 · 95% CI -1.504 to 0.423
  • MK-1029 150 mg vs Placebo · ANOVA · p = 0.865 · Mean difference (final values): 0.079 · 95% CI -0.839 to 0.997
  • Montelukast 10 mg vs Placebo · ANOVA · p = 0.503 · Mean difference (final values): -0.309 · 95% CI -1.219 to 0.600

Adverse events

Collected over Up to 14 weeks (Up to 2 weeks after last dose of study drug). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
MK-1029 10 mg0/58 (0%)0/58 (0%)15/58 (25.9%)
MK-1029 30 mg0/126 (0%)2/126 (1.6%)24/126 (19%)
MK-1029 60 mg0/135 (0%)2/135 (1.5%)27/135 (20%)
MK-1029 150 mg0/52 (0%)1/52 (1.9%)19/52 (36.5%)
Montelukast 10 mg0/60 (0%)0/60 (0%)19/60 (31.7%)
Placebo0/126 (0%)1/126 (0.8%)42/126 (33.3%)
Most frequent serious events
Most frequent serious events
EventMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
HyperglycaemiaMetabolism and nutrition disorders0/580/1260/1351/520/600/126
Kaposi's varicelliform eruptionInfections and infestations0/581/1260/1350/520/600/126
Uterine leiomyomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/581/1260/1350/520/600/126
Tension headacheNervous system disorders0/580/1260/1350/520/601/126
AsthmaRespiratory, thoracic and mediastinal disorders0/581/1260/1350/520/600/126
Cardiac failure congestiveCardiac disorders0/580/1261/1350/520/600/126
PneumoniaInfections and infestations0/580/1261/1350/520/600/126
Respiratory failureRespiratory, thoracic and mediastinal disorders0/580/1261/1350/520/600/126
Most frequent other events
Most frequent other events
EventMK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlacebo
AsthmaRespiratory, thoracic and mediastinal disorders4/5815/1265/1358/5211/6017/126
NasopharyngitisInfections and infestations4/586/12610/1357/525/6012/126
Accidental overdoseInjury, poisoning and procedural complications4/582/1267/1351/522/606/126
DiarrhoeaGastrointestinal disorders0/584/1262/1353/520/603/126
BronchitisInfections and infestations1/582/1262/1353/521/603/126
CystitisInfections and infestations0/581/1262/1353/520/602/126
GastroenteritisInfections and infestations3/580/1261/1352/520/602/126

Baseline characteristics

All Randomized Participants

Age, Continuous
Age, Continuous(Years)MK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlaceboTotal
Mean39.9 ± 13.244.3 ± 12.443 ± 13.241.7 ± 12.243.7 ± 13.341.1 ± 12.442.5 ± 12.8
Sex: Female, Male
Sex: Female, Male(Participants)MK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlaceboTotal
Female337877313247298
Male274965222887278
Asthma Phenotype
Asthma Phenotype(Participants)MK-1029 10 mgMK-1029 30 mgMK-1029 60 mgMK-1029 150 mgMontelukast 10 mgPlaceboTotal
Th2-High585047526058325
Th2-Low076880068232
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Study locations

No study locations are listed for this record.

09

References and documents

Individual participant data

Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

No publications or documents are linked to this record.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 13, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01656395
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Aug 3, 2012
Start date
Aug 23, 2012
Primary completion
Jun 10, 2014
Completion
Jul 8, 2014
Results posted
Sep 13, 2018
Last update
Sep 13, 2018

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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