Asthma
Conditions
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.
Interventions
DRUGMK-1029
MK-1029 10 mg, 30 mg or 150 mg oral tablets taken QD at bedtime, based on randomization.
Parts I-II: Participants will receive Montelukast 10 mg tablets QD
DRUGPlacebo
Parts I-II: Participants will receive Placebo tablets QD
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline and last six weeks of treatment (visits at Week 6, Week 8, Week 10 and Week 12) | 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. |
| Percentage of Participants Who Experience Adverse Events (AEs) | Up to 14 weeks | 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. |
| Percentage of Participants Who Discontinue Study Due to AEs | Up to 14 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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. |
| 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) | 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. |
| Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Baseline and Week 12 | 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. |
| Percentage of Asthma Exacerbation Days | Week 6 to Week 12 | 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. |
| Change From Baseline in Asthma Control Questionnaire (ACQ) Score | Baseline and Week 12 | 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. |
| Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score | Baseline and Week 12 | 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. |
| Percentage of Asthma Attack Days | Week 6 to Week 12 | 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. |
| Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Baseline and Week 12 | 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. |
| 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) | 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. |
| 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) | 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. |
Participant flow
Pre-assignment details
Out of 576 randomized participants, 557 received treatment. The planned MK-1029 1 or 3 mg arm and the Montelukast + MK-1029 arm did not enroll any participants.
Participants by arm
| Arm | Count |
|---|---|
| MK-1029 10 mg Participants receive MK-1029 10 mg tablets once daily (QD) for 12 weeks | 60 |
| MK-1029 30 mg Participants receive MK-1029 30 mg tablets QD for 12 weeks | 127 |
| MK-1029 60 mg Participants receive MK-1029 two 30 mg tablets QD for 12 weeks | 142 |
| MK-1029 150 mg Participants receive MK-1029 150 mg tablets QD for 12 weeks | 53 |
| Montelukast 10 mg Participants receive Montelukast 10 mg tablets QD for 12 weeks | 60 |
| Placebo Participants receive Placebo tablets QD for 12 weeks | 134 |
| Total | 576 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 14 | 5 | 4 | 5 | 7 | 0 | 0 |
| Overall Study | Lack of Efficacy | 1 | 8 | 6 | 1 | 1 | 6 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Non-Compliance with Study Drug | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 2 | 3 | 3 | 2 | 3 | 3 | 0 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 6 | 6 | 9 | 2 | 4 | 10 | 0 | 0 |
| Overall Study | Screen Failure | 2 | 1 | 7 | 1 | 0 | 8 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 4 | 2 | 0 | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | MK-1029 10 mg | MK-1029 30 mg | MK-1029 60 mg | MK-1029 150 mg | Montelukast 10 mg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 39.9 Years STANDARD_DEVIATION 13.2 | 44.3 Years STANDARD_DEVIATION 12.4 | 43 Years STANDARD_DEVIATION 13.2 | 41.7 Years STANDARD_DEVIATION 12.2 | 43.7 Years STANDARD_DEVIATION 13.3 | 41.1 Years STANDARD_DEVIATION 12.4 | 42.5 Years STANDARD_DEVIATION 12.8 |
| Asthma Phenotype Th2-High | 58 Participants | 50 Participants | 47 Participants | 52 Participants | 60 Participants | 58 Participants | 325 Participants |
| Asthma Phenotype Th2-Low | 0 Participants | 76 Participants | 88 Participants | 0 Participants | 0 Participants | 68 Participants | 232 Participants |
| Sex: Female, Male Female | 33 Participants | 78 Participants | 77 Participants | 31 Participants | 32 Participants | 47 Participants | 298 Participants |
| Sex: Female, Male Male | 27 Participants | 49 Participants | 65 Participants | 22 Participants | 28 Participants | 87 Participants | 278 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 126 | 0 / 135 | 0 / 52 | 0 / 60 | 0 / 126 |
| other Total, other adverse events | 15 / 58 | 24 / 126 | 27 / 135 | 19 / 52 | 19 / 60 | 42 / 126 |
| serious Total, serious adverse events | 0 / 58 | 2 / 126 | 2 / 135 | 1 / 52 | 0 / 60 | 1 / 126 |
Outcome results
Primary
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)
Population: T helper cell type 2 (TH2)-High participants who received ≥1 study drug dose and had FEV1 data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1029 10 mg | Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | 0.065 Liters |
| MK-1029 30 mg | Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | 0.004 Liters |
| MK-1029 60 mg | Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | 0.063 Liters |
| MK-1029 150 mg | Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | 0.036 Liters |
| Montelukast 10 mg | Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | 0.039 Liters |
| Placebo | Average Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | 0.043 Liters |
Comparison: Difference in least squares (LS) means for average change from Baseline over Week 6 to Week 12 in FEV1: MK-1029 10 mg vs. Placebo. Constrained longitudinal data analysis (cLDA) model includes terms for visit as categorical variable, prior inhaled corticosteroid (ICS) use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.68595% CI: [-0.084, 0.127]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in FEV1: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.47795% CI: [-0.149, 0.07]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in FEV1: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.73395% CI: [-0.092, 0.13]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in FEV1: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.8995% CI: [-0.115, 0.1]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in FEV1: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.93595% CI: [-0.109, 0.1]cLDA model
Primary
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
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1029 10 mg | Percentage of Participants Who Discontinue Study Due to AEs | 1.7 Percentage of participants |
| MK-1029 30 mg | Percentage of Participants Who Discontinue Study Due to AEs | 10.3 Percentage of participants |
| MK-1029 60 mg | Percentage of Participants Who Discontinue Study Due to AEs | 3.7 Percentage of participants |
| MK-1029 150 mg | Percentage of Participants Who Discontinue Study Due to AEs | 7.7 Percentage of participants |
| Montelukast 10 mg | Percentage of Participants Who Discontinue Study Due to AEs | 8.3 Percentage of participants |
| Placebo | Percentage of Participants Who Discontinue Study Due to AEs | 5.6 Percentage of participants |
Primary
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
Population: All randomized participants who received ≥1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1029 10 mg | Percentage of Participants Who Experience Adverse Events (AEs) | 44.8 Percentage of participants |
| MK-1029 30 mg | Percentage of Participants Who Experience Adverse Events (AEs) | 48.4 Percentage of participants |
| MK-1029 60 mg | Percentage of Participants Who Experience Adverse Events (AEs) | 47.4 Percentage of participants |
| MK-1029 150 mg | Percentage of Participants Who Experience Adverse Events (AEs) | 53.8 Percentage of participants |
| Montelukast 10 mg | Percentage of Participants Who Experience Adverse Events (AEs) | 56.7 Percentage of participants |
| Placebo | Percentage of Participants Who Experience Adverse Events (AEs) | 57.9 Percentage of participants |
Secondary
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)
Population: TH2-High participants who received ≥1 study drug dose and had DSS data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1029 10 mg | Average Change From Baseline in Daytime Symptom Score (DSS) | -0.398 Score on a scale |
| MK-1029 30 mg | Average Change From Baseline in Daytime Symptom Score (DSS) | -0.134 Score on a scale |
| MK-1029 60 mg | Average Change From Baseline in Daytime Symptom Score (DSS) | -0.364 Score on a scale |
| MK-1029 150 mg | Average Change From Baseline in Daytime Symptom Score (DSS) | -0.120 Score on a scale |
| Montelukast 10 mg | Average Change From Baseline in Daytime Symptom Score (DSS) | -0.411 Score on a scale |
| Placebo | Average Change From Baseline in Daytime Symptom Score (DSS) | -0.276 Score on a scale |
Comparison: Difference in LS means for average change from Baseline to Week 12 in DSS: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.42995% CI: [-0.427, 0.182]cLDA model
Comparison: Difference in LS means for average change from Baseline to Week 12 in DSS: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.3795% CI: [-0.169, 0.454]cLDA model
Comparison: Difference in LS means for average change from Baseline to Week 12 in DSS: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK- 1029 or Montelukast).p-value: 0.57995% CI: [-0.402, 0.225]cLDA model
Comparison: Difference in LS means for average change from Baseline to Week 12 in DSS: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.30595% CI: [-0.142, 0.454]cLDA model
Comparison: Difference in LS means for average change from Baseline to Week 12 in DSS: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.37295% CI: [-0.434, 0.163]cLDA model
Secondary
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)
Population: TH2-High participants who received ≥1 study drug dose and had AM/PM PEF data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1029 10 mg | Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF) | -1.857 Liters/minutes |
| MK-1029 30 mg | Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF) | 3.850 Liters/minutes |
| MK-1029 60 mg | Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF) | 7.174 Liters/minutes |
| MK-1029 150 mg | Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF) | 2.713 Liters/minutes |
| Montelukast 10 mg | Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF) | -4.005 Liters/minutes |
| Placebo | Average Change From Baseline in Morning/Evening Peak Expiratory Flow (AM/PM PEF) | -2.401 Liters/minutes |
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.95895% CI: [-19.92, 21.007]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: MK- 1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.55995% CI: [-14.81, 27.307]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.37495% CI: [-11.62, 30.766]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.61895% CI: [-15.04, 25.272]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in AM/PM PEF: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.87695% CI: [-21.76, 18.554]cLDA model
Secondary
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)
Population: TH2-High participants who received ≥1 study drug dose and had nocturnal awakening data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1029 10 mg | Average Change From Baseline in Number of Nocturnal Awakenings | -1.277 Number of awakenings |
| MK-1029 30 mg | Average Change From Baseline in Number of Nocturnal Awakenings | -0.900 Number of awakenings |
| MK-1029 60 mg | Average Change From Baseline in Number of Nocturnal Awakenings | -1.286 Number of awakenings |
| MK-1029 150 mg | Average Change From Baseline in Number of Nocturnal Awakenings | -1.277 Number of awakenings |
| Montelukast 10 mg | Average Change From Baseline in Number of Nocturnal Awakenings | -1.107 Number of awakenings |
| Placebo | Average Change From Baseline in Number of Nocturnal Awakenings | -1.036 Number of awakenings |
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.56595% CI: [-1.066, 0.583]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.75495% CI: [-0.713, 0.983]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.56395% CI: [-1.104, 0.603]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.55995% CI: [-1.053, 0.571]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in nocturnal awakenings: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.86395% CI: [-0.883, 0.741]cLDA model
Secondary
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)
Population: TH2-High participants who received ≥1 study drug dose and had SABA usage data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1029 10 mg | Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs) | -1.373 Number of SABA Puffs |
| MK-1029 30 mg | Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs) | -0.920 Number of SABA Puffs |
| MK-1029 60 mg | Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs) | -0.955 Number of SABA Puffs |
| MK-1029 150 mg | Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs) | -0.571 Number of SABA Puffs |
| Montelukast 10 mg | Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs) | -1.234 Number of SABA Puffs |
| Placebo | Average Change From Baseline in Use of Short-Acting Beta-Agonists (SABAs) | -0.845 Number of SABA Puffs |
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use(Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.11495% CI: [-1.184, 0.128]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.82795% CI: [-0.75, 0.6]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.7595% CI: [-0.789, 0.569]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.40395% CI: [-0.371, 0.921]cLDA model
Comparison: Difference in LS means for average change from Baseline over Week 6 to Week 12 in SABA use: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.23795% CI: [-1.035, 0.257]cLDA model
Secondary
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
Population: TH2-High participants who received ≥1 study drug dose and had ACQ data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1029 10 mg | Change From Baseline in Asthma Control Questionnaire (ACQ) Score | -0.807 Score on a scale |
| MK-1029 30 mg | Change From Baseline in Asthma Control Questionnaire (ACQ) Score | -0.736 Score on a scale |
| MK-1029 60 mg | Change From Baseline in Asthma Control Questionnaire (ACQ) Score | -0.855 Score on a scale |
| MK-1029 150 mg | Change From Baseline in Asthma Control Questionnaire (ACQ) Score | -1.066 Score on a scale |
| Montelukast 10 mg | Change From Baseline in Asthma Control Questionnaire (ACQ) Score | -0.931 Score on a scale |
| Placebo | Change From Baseline in Asthma Control Questionnaire (ACQ) Score | -0.704 Score on a scale |
Comparison: Difference in LS means for change from Baseline to Week 12 in ACQ Score: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.60395% CI: [-0.495, 0.288]cLDA model
Comparison: Difference in LS means for change from Baseline to Week 12 in ACQ Score: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.87595% CI: [-0.436, 0.372]cLDA model
Comparison: Difference in LS means for change from Baseline to Week 12 in ACQ Score: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.47695% CI: [-0.568, 0.265]cLDA model
Comparison: Difference in LS means for change from Baseline to Week 12 in ACQ Score: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.07995% CI: [-0.767, 0.042]cLDA model
Comparison: Difference in LS means for change from Baseline to Week 12 in ACQ Score: Montelukast vs. Placebo.~cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.25795% CI: [-0.621, 0.166]cLDA model
Secondary
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
Population: TH2-High participants who received ≥1 study drug dose and had AQLQ(S) data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MK-1029 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Emotional Function Domain | 0.55 Score on a scale | Standard Deviation 1.35 |
| MK-1029 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Environmental Stimuli Domain | 0.53 Score on a scale | Standard Deviation 1.19 |
| MK-1029 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Overall Score | 0.533 Score on a scale | Standard Deviation 1.007 |
| MK-1029 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Activity Domain | 0.46 Score on a scale | Standard Deviation 1.05 |
| MK-1029 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Symptoms Domain | 0.59 Score on a scale | Standard Deviation 1.2 |
| MK-1029 30 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Overall Score | 0.256 Score on a scale | Standard Deviation 0.997 |
| MK-1029 30 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Emotional Function Domain | 0.06 Score on a scale | Standard Deviation 1.17 |
| MK-1029 30 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Symptoms Domain | 0.34 Score on a scale | Standard Deviation 1.24 |
| MK-1029 30 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Activity Domain | 0.27 Score on a scale | Standard Deviation 0.98 |
| MK-1029 30 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Environmental Stimuli Domain | 0.21 Score on a scale | Standard Deviation 0.9 |
| MK-1029 60 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Activity Domain | 0.62 Score on a scale | Standard Deviation 1.08 |
| MK-1029 60 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Environmental Stimuli Domain | 0.54 Score on a scale | Standard Deviation 1.2 |
| MK-1029 60 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Emotional Function Domain | 0.75 Score on a scale | Standard Deviation 1.26 |
| MK-1029 60 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Symptoms Domain | 0.80 Score on a scale | Standard Deviation 1.12 |
| MK-1029 60 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Overall Score | 0.696 Score on a scale | Standard Deviation 1.04 |
| MK-1029 150 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Symptoms Domain | 1.02 Score on a scale | Standard Deviation 1.25 |
| MK-1029 150 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Environmental Stimuli Domain | 0.89 Score on a scale | Standard Deviation 1.47 |
| MK-1029 150 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Overall Score | 0.999 Score on a scale | Standard Deviation 1.255 |
| MK-1029 150 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Activity Domain | 0.96 Score on a scale | Standard Deviation 1.32 |
| MK-1029 150 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Emotional Function Domain | 1.12 Score on a scale | Standard Deviation 1.62 |
| Montelukast 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Symptoms Domain | 0.83 Score on a scale | Standard Deviation 1.11 |
| Montelukast 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Overall Score | 0.736 Score on a scale | Standard Deviation 1.028 |
| Montelukast 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Environmental Stimuli Domain | 0.70 Score on a scale | Standard Deviation 1.18 |
| Montelukast 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Emotional Function Domain | 0.70 Score on a scale | Standard Deviation 1.2 |
| Montelukast 10 mg | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Activity Domain | 0.66 Score on a scale | Standard Deviation 1.03 |
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Emotional Function Domain | 0.45 Score on a scale | Standard Deviation 1.37 |
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Overall Score | 0.458 Score on a scale | Standard Deviation 1.176 |
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Activity Domain | 0.44 Score on a scale | Standard Deviation 1.18 |
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Symptoms Domain | 0.47 Score on a scale | Standard Deviation 1.29 |
| Placebo | Change From Baseline in Asthma Quality of Life Questionnaire With Standardised Activities [AQLQ(S)] Overall and Domain Scores | Environmental Stimuli Domain | 0.49 Score on a scale | Standard Deviation 1.43 |
Comparison: Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: MK-1029 10 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.68295% CI: [-0.288, 0.44]cLDA model
Comparison: Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: MK-1029 30 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.80795% CI: [-0.422, 0.329]cLDA model
Comparison: Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: MK-1029 60 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.40395% CI: [-0.222, 0.552]cLDA model
Comparison: Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: MK-1029 150 mg vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.05195% CI: [-0.001, 0.751]cLDA model
Comparison: Difference in LS means for change from Baseline to Week 12 in AQLQ(S) Overall Score: Montelukast vs. Placebo. cLDA model includes terms for visit as categorical variable, prior ICS use (Yes/No) and treatment by visit. Positive differences are in favor of the first treatment group in the comparison (MK- 1029 or Montelukast).p-value: 0.08695% CI: [-0.045, 0.683]cLDA model
Secondary
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
Population: TH2-High participants who received ≥1 study drug dose and had asthma attack data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1029 10 mg | Percentage of Asthma Attack Days | 0.482 Percentage |
| MK-1029 30 mg | Percentage of Asthma Attack Days | 0.182 Percentage |
| MK-1029 60 mg | Percentage of Asthma Attack Days | 0.017 Percentage |
| MK-1029 150 mg | Percentage of Asthma Attack Days | 0.637 Percentage |
| Montelukast 10 mg | Percentage of Asthma Attack Days | 0.248 Percentage |
| Placebo | Percentage of Asthma Attack Days | 0.557 Percentage |
Comparison: Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: MK-1209 10 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK- 1029 or Montelukast).p-value: 0.87395% CI: [-1.004, 0.853]ANOVA
Comparison: Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: MK-1209 30 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.43795% CI: [-1.326, 0.575]ANOVA
Comparison: Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: MK-1209 60 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.2795% CI: [-1.504, 0.423]ANOVA
Comparison: Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: MK-1209 150 mg vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.86595% CI: [-0.839, 0.997]ANOVA
Comparison: Difference in LS means for percent of asthma attack days over Week 6 to Week 12 of a 12-week treatment period: Montelukast vs. Placebo. ANOVA model includes terms for prior ICS use (Yes/No) and treatment. Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.50395% CI: [-1.219, 0.6]ANOVA
Secondary
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
Population: TH2-High participants who received ≥1 study drug dose and had asthma exacerbation data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| MK-1029 10 mg | Percentage of Asthma Exacerbation Days | 17.704 Percentage of Asthma Exacerbation Days |
| MK-1029 30 mg | Percentage of Asthma Exacerbation Days | 15.812 Percentage of Asthma Exacerbation Days |
| MK-1029 60 mg | Percentage of Asthma Exacerbation Days | 15.435 Percentage of Asthma Exacerbation Days |
| MK-1029 150 mg | Percentage of Asthma Exacerbation Days | 20.238 Percentage of Asthma Exacerbation Days |
| Montelukast 10 mg | Percentage of Asthma Exacerbation Days | 19.657 Percentage of Asthma Exacerbation Days |
| Placebo | Percentage of Asthma Exacerbation Days | 24.904 Percentage of Asthma Exacerbation Days |
Comparison: Difference in LS means for percent of asthma exacerbation day over Week 6 through Week 12: MK- 1029 10 mg vs. Placebo. Analysis of variance (ANOVA) model includes the terms for treatment groups and prior ICS use (Yes/No). Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.16995% CI: [-17.48, 3.08]ANOVA
Comparison: Difference in LS means for percent of asthma exacerbation day over Week 6 through Week 12: MK- 1029 30 mg vs. Placebo. ANOVA model includes the terms for treatment groups and prior ICS use (Yes/No). Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.09295% CI: [-19.67, 1.485]ANOVA
Comparison: Difference in LS means for percent of asthma exacerbation day over Week 6 through Week 12: MK- 1029 60 mg vs. Placebo. ANOVA model includes the terms for treatment groups and prior ICS use (Yes/No). Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.08395% CI: [-20.19, 1.25]ANOVA
Comparison: Difference in LS means for percent of asthma exacerbation day over Week 6 through Week 12: MK- 1029 150 mg vs. Placebo. ANOVA model includes the terms for treatment groups and prior ICS use (Yes/No). Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.36795% CI: [-14.83, 5.501]ANOVA
Comparison: Difference in LS means for percent of asthma exacerbation day over Week 6 through Week 12: Montelukast vs. Placebo. ANOVA model includes the terms for treatment groups and prior ICS use (Yes/No). Negative differences are in favor of the first treatment group in the comparison (MK-1029 or Montelukast).p-value: 0.30895% CI: [-15.36, 4.871]ANOVA
Secondary
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
Population: TH2-High participants who received ≥1 study drug dose and had ACQ data at Week 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1029 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score | 65.51 Percentage of participants |
| MK-1029 30 mg | Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score | 59.57 Percentage of participants |
| MK-1029 60 mg | Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score | 66.60 Percentage of participants |
| MK-1029 150 mg | Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score | 71.11 Percentage of participants |
| Montelukast 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score | 64.72 Percentage of participants |
| Placebo | Percentage of Participants With a ≥0.5 Change From Baseline in ACQ Score | 62.43 Percentage of participants |
Comparison: Difference for change from Baseline to Week 12 in ACQ response rate: MK-1029 10 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).p-value: 0.74295% CI: [-15.1, 21.1]MN method
Comparison: Difference for change from Baseline to Week 12 in ACQ response rate: MK-1029 30 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).p-value: 0.724895% CI: [-22.1, 15.4]MN method
Comparison: Difference for change from Baseline to Week 12 in ACQ response rate: MK-1029 60 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).p-value: 0.699195% CI: [-15.6, 22.6]MN method
Comparison: Difference for change from Baseline to Week 12 in ACQ response rate: MK-1029 150 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).p-value: 0.393495% CI: [-10.6, 26.2]MN method
Comparison: Difference for change from Baseline to Week 12 in ACQ response rate: Montelukast vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).p-value: 0.803295% CI: [-16, 20.5]MN method
Secondary
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
Population: TH2-High participants who received ≥1 study drug dose and had AQLQ(S) data at Week 12.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-1029 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Emotional Function Domain | 56.19 Percentage of participants |
| MK-1029 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Overall Score | 48.99 Percentage of participants |
| MK-1029 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Activity Domain | 47.19 Percentage of participants |
| MK-1029 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Environmental Stimuli Domain | 41.79 Percentage of participants |
| MK-1029 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Symptoms Domain | 52.59 Percentage of participants |
| MK-1029 30 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Activity Domain | 40.46 Percentage of participants |
| MK-1029 30 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Overall Score | 40.49 Percentage of participants |
| MK-1029 30 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Emotional Function Domain | 31.95 Percentage of participants |
| MK-1029 30 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Symptoms Domain | 42.63 Percentage of participants |
| MK-1029 30 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Environmental Stimuli Domain | 42.60 Percentage of participants |
| MK-1029 60 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Environmental Stimuli Domain | 59.66 Percentage of participants |
| MK-1029 60 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Activity Domain | 50.00 Percentage of participants |
| MK-1029 60 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Overall Score | 57.22 Percentage of participants |
| MK-1029 60 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Emotional Function Domain | 62.10 Percentage of participants |
| MK-1029 60 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Symptoms Domain | 59.66 Percentage of participants |
| MK-1029 150 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Symptoms Domain | 57.76 Percentage of participants |
| MK-1029 150 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Emotional Function Domain | 57.76 Percentage of participants |
| MK-1029 150 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Environmental Stimuli Domain | 59.97 Percentage of participants |
| MK-1029 150 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Overall Score | 64.48 Percentage of participants |
| MK-1029 150 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Activity Domain | 60.07 Percentage of participants |
| Montelukast 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Environmental Stimuli Domain | 53.16 Percentage of participants |
| Montelukast 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Symptoms Domain | 64.08 Percentage of participants |
| Montelukast 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Emotional Function Domain | 53.91 Percentage of participants |
| Montelukast 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Overall Score | 64.08 Percentage of participants |
| Montelukast 10 mg | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Activity Domain | 52.36 Percentage of participants |
| Placebo | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Symptoms Domain | 48.13 Percentage of participants |
| Placebo | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Activity Domain | 42.61 Percentage of participants |
| Placebo | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Environmental Stimuli Domain | 48.13 Percentage of participants |
| Placebo | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Emotional Function Domain | 49.90 Percentage of participants |
| Placebo | Percentage of Participants With a ≥0.5 Change From Baseline in AQLQ(S) Overall and Domain Scores | Overall Score | 46.14 Percentage of participants |
Comparison: Difference for AQLQ(S) Response Rate: MK-1029 10 mg vs. Placebo. P-values, estimates and 95% confidence intervals (CIs) are based on the Miettinen and Nurminen (MN) method stratified by prior ICS use (Yes/No).p-value: 0.768795% CI: [-16, 21.3]MN method
Comparison: Difference for AQLQ(S) Response Rate: MK-1029 30 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).p-value: 0.494395% CI: [-24.9, 12.2]MN Method
Comparison: Difference for AQLQ(S) Response Rate: MK-1029 60 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).p-value: 0.300395% CI: [-9.4, 29.6]MN method
Comparison: Difference for AQLQ(S) Response Rate: MK-1029 150 mg vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).p-value: 0.077495% CI: [-1.9, 35.7]MN method
Comparison: Difference for AQLQ(S) Response Rate: Montelukast vs. Placebo. P-values, estimates and 95% CIs are based on the MN method stratified by prior ICS use (Yes/No).p-value: 0.055595% CI: [-0.4, 35.5]MN method