Back to resultsStudy to Evaluate the Effectiveness and Safety of MK-1029 in the Treatment of Persistent Asthma That is Not Controlled With Montelukast (ML) in Adults (MK-1029-011)
Primary Purpose
Asthma
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
MK-1029
Placebo
Montelukast (ML)
Sponsored by
About this trial
This is an interventional treatment trial for Asthma
Eligibility Criteria
Inclusion Criteria:
- not pregnant or breastfeeding and does not plan to become pregnant for the duration of the study;
- symptoms of persistent asthma for at least one year;
- current use of asthma treatments: 1) "as-needed" inhaled SABAs (albuterol/salbutamol) and no asthma controller for at least 4 weeks prior to Screening Visit OR 2) stable dose of ICS, combination ICS/LABA and/or oral asthma controller(s) for at least 4 weeks prior to Screening Visit and able to tolerate discontinuing all controllers while receiving ML;
- no history of smoking OR no smoking for at least 1 year, with a smoking history of no more than 10 pack-years;
- able to maintain a constant day/night, awake/sleep cycle;
- agrees to not change habitual consumption of beverages or foods containing caffeine throughout the study;
- Body Mass Index (BMI) of 15 kg/m^2 to 40 kg/m^2.
Exclusion Criteria:
- history of myocardial infarction, congestive heart failure, or uncontrolled cardiac arrhythmia within 3 months prior to Screening Visit;
- hospitalized or hospitalization within 4 weeks prior to Screening Visit;
- intention of moving or anticipation of missing any study visits;
- any major surgical procedure(s) within 4 weeks prior to Screening Visit;
- participation in a clinical trial involving an investigational drug within 4 weeks prior to Screening Visit;
- current regular use or a recent past abuse (within past 5 years) of alcohol (>14 drinks/week) or illicit drugs;
- donation of a unit of blood within 2 weeks prior to Screening Visit or intention of donating a unit of blood during the study;
- evidence of another active pulmonary disorder such as bronchiectasis or COPD;
- treatment in an emergency room for asthma within 4 weeks prior to Screening Visit or hospitalization for asthma within 2 months prior to Screening Visit;
- respiratory tract infection which required treatment with antibiotics within 2 months prior to Screening Visit;
- evidence of active sinus disease within 1 week prior to Screening Visit;
- history of a psychiatric disorder, other than stable depression, within 3 months prior to Screening Visit;
- history of human immunodeficiency virus (HIV);
- hypersensitivity or intolerance to inhaled beta-agonists and/or leukotriene inhibitors or any of their ingredients, including lactose and galactose;
- unstable disease of the ophthalmologic, neurological, hepatic, renal, connective tissue, genitourinary, gastrointestinal, cardiovascular or hematologic systems;
- cancer (except for successfully treated basal and squamous cell carcinomas of the skin) or history of cancer within 5 years prior to Screening Visit;
- uncontrolled hypertension.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
MK-1029/Placebo
Placebo/MK-1029
Arm Description
Participants received 4 weeks treatment with MK-1029 150 mg once daily (QD) + ML 10 mg QD in Period III and Placebo QD + ML 10 mg QD in Period V. Period IV was a 4-week wash-out period during which participants received single-blind Placebo QD and open-label ML 10 mg QD.
Participants received 4 weeks treatment with Placebo QD + ML 10 mg QD in Period III and MK-1029 150 mg QD + ML 10 mg QD in Period V. Period IV was a 4-week wash-out period during which participants received single-blind Placebo QD and open-label ML 10 mg QD.
Outcomes
Primary Outcome Measures
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 4
The change from baseline in FEV1 at Week 4 following treatment with MK-1029 + ML or placebo + ML was assessed. The pre-bronchodilator FEV1 was evaluated to assess the response to treatment for asthma. The primary efficacy evaluation period was the last week of each treatment period: Period III (Initial Therapy, Week 4) and Period V (Crossover Therapy, Week 4). The change from baseline in FEV1 was evaluated using a longitudinal data analysis (LDA) model with repeated measurements of FEV1, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect. Baseline FEV1 is defined as the measurement taken before dosing in each treatment period (i. e., at Visit 3 [Week 0], prior to Period III and at Visit 6 [Week 8], prior to Period V). The Baseline Characteristics section shows FEV1 values at baseline.
Adverse Events During Treatment and Follow-up
The number of participants who had at least one adverse event (AE) during study treatment and follow-up was assessed. 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 SPONSOR's product, whether or not considered related to the use of the product. The number of participants with at least one AE was assessed. The number of participants in any treatment group with at least one AE was assessed.
Discontinuation of Treatment Due to An Adverse Event
The number of participants who discontinued study treatment due to an AE was assessed. 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 SPONSOR's product, whether or not considered related to the use of the product.
Secondary Outcome Measures
Change From Baseline in Daytime Symptom Score (DSS) at Week 4
The change from baseline in DSS at Week 4 following treatment was assessed. Participants used an electronic diary (e-Diary) to enter their asthma symptom scores every evening. Participants scored daily symptoms (chest discomfort, wheezing, shortness of breath, and cough) by responding to 4 questions: 1) Symptom frequency (0 = None of the time, 6 = All of the time); 2) Bothersomeness (0 = Not bothered, 6 = Severely bothered); 3) Activity limitation (0 = Not limited, 6 = Totally limited); 4) Frequency of activity limitation (0 = None of the time, 6 = All of the time). The average of the 4 scores for overall DSS ranges from 0 to 6 where a higher average indicates greater symptom severity. The average overall DSS was calculated over the week-long assessment periods. The change from baseline in DSS was evaluated using the LDA model with repeated measurements of DSS, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Change From Baseline in Short-Acting Beta Agonist (SABA) Use at Week 4
The change from baseline in SABA use at Week 4 after treatment with MK-1029 + ML or placebo + ML was assessed. Participants used the e-Diary upon arising and before going to sleep to enter the total number of SABA puffs used for asthma relief. The number of SABA puffs recorded was the number of canister actuations (e. g., when SABA use was required and 3 puffs were inhaled, this was recorded as 3). Participants also recorded the number of nebulizer treatments (1 nebulized SABA use = 3 puffs). The average daily number of puffs for an individual participant was calculated over the week-long assessment periods. The change from baseline in SABA use was evaluated using the LDA model with repeated measurements of SABA use, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Change From Baseline in Nocturnal Awakenings at Week 4
The change from baseline in nocturnal awakenings due to asthma at Week 4 after treatment with MK-1029 + ML or placebo + ML was assessed. The participant scored nocturnal awakenings by answering the question, "Did you wake up with asthma symptoms in the middle of the night or upon awakening in the morning?" (No or Yes). Participants recorded in the e-Diary the number of nights per week in which they awakened with asthma, as determined by dividing the number of nights of awakening with asthma by the total number of nights and then multiplying by 7 (standardized to a 7-day period). The change from baseline in nocturnal awakenings was evaluated using the LDA model with repeated measurements of nocturnal awakenings, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Change From Baseline in Morning (AM) Peak Expiratory Flow (PEF) at Week 4
The change from baseline in AM PEF at Week 4 after treatment with MK-1029 + ML or placebo + ML was assessed in 97 participants. Participants performed triplicate AM PEF measurements in the morning upon rising. Participants entered all 3 measurements and the greatest AM PEF value was recorded by the e-Diary. Participants refrained from SABA use within the 4 hours prior to performing PEF measurements. The average AM PEF for an individual participant was calculated over the week-long assessment periods. The change from baseline in AM PEF was evaluated using the LDA model with repeated measurements of AM PEF, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Change From Baseline in Evening (PM) PEF at Week 4
The change from baseline in PM PEF at Week 4 after treatment with MK-1029 + ML or placebo + ML was assessed. Participants performed triplicate PM PEF measurements in the evening, immediately before study drug administration, at bedtime. Participants entered all 3 measurements and the greatest PM PEF value was recorded by the e-Diary. Participants refrained from SABA use within the 4 hours prior to performing PEF measurements. The average PM PEF for an individual participant was calculated over the week-long assessment periods. The change from baseline in PM PEF was evaluated using the LDA model with repeated measurements of PM PEF, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Change From Baseline in Asthma Control Questionnaire (ACQ) Score at Week 4
The change from baseline in the ACQ score at Week 4, after treatment, was assessed in 97 participants. Participants completed 6 items of the ACQ (i. e., ACQ-6) and provided the average of responses over the past week: 1) Frequency of nocturnal awakenings (0 = Never, 6 = Unable to sleep); 2) Symptom severity (0 = None, 6 = Very severe); 3) Activity limitations (0 = Not limited, 6 = Totally limited); 4) Breathlessness (0 = None, 6 = Very great deal); 5) Wheezing (0 = Not at all, 6 = All the time); 6) Daily SABA use (0 = None, 6 = More than 16 puffs on most days). The ACQ score ranges from 0 to 6 where a lower score indicates greater performance. The investigator reviewed the participant-completed ACQ-6 to ensure its completeness. The change from baseline in the ACQ score was evaluated using the LDA model with repeated measurements of the ACQ score, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Full Information
NCT ID
NCT01624974
First Posted
June 19, 2012
Last Updated
December 10, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01624974
Brief Title
Study to Evaluate the Effectiveness and Safety of MK-1029 in the Treatment of Persistent Asthma That is Not Controlled With Montelukast (ML) in Adults (MK-1029-011)
Official Title
A Double-Blind, Randomized, Placebo-Controlled, Multicenter, Crossover Study of MK-1029 in Adult Subjects With Persistent Asthma Who Remain Uncontrolled While Being Maintained on Montelukast
Study Type
Interventional
2. Study Status
Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
August 9, 2012 (Actual)
Primary Completion Date
May 5, 2014 (Actual)
Study Completion Date
May 5, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the effect of MK-1029 on lung function in the treatment of adults who have persistent asthma that is uncontrolled with the use of montelukast (ML). Participants will use randomized study drug (either MK-1029 or placebo) for two separate 4-week treatment periods. All participants will also use ML during the treatment periods. The primary hypothesis is that MK-1029 is superior to placebo in change from baseline in forced expiratory volume in one second (FEV1) at the end of the 4-week treatment period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
107 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MK-1029/Placebo
Arm Type
Experimental
Arm Description
Participants received 4 weeks treatment with MK-1029 150 mg once daily (QD) + ML 10 mg QD in Period III and Placebo QD + ML 10 mg QD in Period V. Period IV was a 4-week wash-out period during which participants received single-blind Placebo QD and open-label ML 10 mg QD.
Arm Title
Placebo/MK-1029
Arm Type
Experimental
Arm Description
Participants received 4 weeks treatment with Placebo QD + ML 10 mg QD in Period III and MK-1029 150 mg QD + ML 10 mg QD in Period V. Period IV was a 4-week wash-out period during which participants received single-blind Placebo QD and open-label ML 10 mg QD.
Intervention Type
Drug
Intervention Name(s)
MK-1029
Intervention Description
MK-1029 150 mg tablets taken QD
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets (matching the MK-1029 150 mg tablets) QD
Intervention Type
Drug
Intervention Name(s)
Montelukast (ML)
Intervention Description
ML 10 mg tablets QD
Primary Outcome Measure Information:
Title
Change From Baseline in Forced Expiratory Volume in One Second (FEV1) at Week 4
Description
The change from baseline in FEV1 at Week 4 following treatment with MK-1029 + ML or placebo + ML was assessed. The pre-bronchodilator FEV1 was evaluated to assess the response to treatment for asthma. The primary efficacy evaluation period was the last week of each treatment period: Period III (Initial Therapy, Week 4) and Period V (Crossover Therapy, Week 4). The change from baseline in FEV1 was evaluated using a longitudinal data analysis (LDA) model with repeated measurements of FEV1, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect. Baseline FEV1 is defined as the measurement taken before dosing in each treatment period (i. e., at Visit 3 [Week 0], prior to Period III and at Visit 6 [Week 8], prior to Period V). The Baseline Characteristics section shows FEV1 values at baseline.
Time Frame
The week before the first dose in Period III or V (Baseline) and the last week of Period III or V
Title
Adverse Events During Treatment and Follow-up
Description
The number of participants who had at least one adverse event (AE) during study treatment and follow-up was assessed. 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 SPONSOR's product, whether or not considered related to the use of the product. The number of participants with at least one AE was assessed. The number of participants in any treatment group with at least one AE was assessed.
Time Frame
Up to 14 days after the last dose in Period III or Period V (up to 6 weeks)
Title
Discontinuation of Treatment Due to An Adverse Event
Description
The number of participants who discontinued study treatment due to an AE was assessed. 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 SPONSOR's product, whether or not considered related to the use of the product.
Time Frame
Up to the last dose in Period III or Period V (up to 4 weeks)
Secondary Outcome Measure Information:
Title
Change From Baseline in Daytime Symptom Score (DSS) at Week 4
Description
The change from baseline in DSS at Week 4 following treatment was assessed. Participants used an electronic diary (e-Diary) to enter their asthma symptom scores every evening. Participants scored daily symptoms (chest discomfort, wheezing, shortness of breath, and cough) by responding to 4 questions: 1) Symptom frequency (0 = None of the time, 6 = All of the time); 2) Bothersomeness (0 = Not bothered, 6 = Severely bothered); 3) Activity limitation (0 = Not limited, 6 = Totally limited); 4) Frequency of activity limitation (0 = None of the time, 6 = All of the time). The average of the 4 scores for overall DSS ranges from 0 to 6 where a higher average indicates greater symptom severity. The average overall DSS was calculated over the week-long assessment periods. The change from baseline in DSS was evaluated using the LDA model with repeated measurements of DSS, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Time Frame
The week before the first dose in Period III or V (Baseline) and the last week of Period III or V
Title
Change From Baseline in Short-Acting Beta Agonist (SABA) Use at Week 4
Description
The change from baseline in SABA use at Week 4 after treatment with MK-1029 + ML or placebo + ML was assessed. Participants used the e-Diary upon arising and before going to sleep to enter the total number of SABA puffs used for asthma relief. The number of SABA puffs recorded was the number of canister actuations (e. g., when SABA use was required and 3 puffs were inhaled, this was recorded as 3). Participants also recorded the number of nebulizer treatments (1 nebulized SABA use = 3 puffs). The average daily number of puffs for an individual participant was calculated over the week-long assessment periods. The change from baseline in SABA use was evaluated using the LDA model with repeated measurements of SABA use, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Time Frame
The week before the first dose in Period III or V (Baseline) and the last week of Period III or V
Title
Change From Baseline in Nocturnal Awakenings at Week 4
Description
The change from baseline in nocturnal awakenings due to asthma at Week 4 after treatment with MK-1029 + ML or placebo + ML was assessed. The participant scored nocturnal awakenings by answering the question, "Did you wake up with asthma symptoms in the middle of the night or upon awakening in the morning?" (No or Yes). Participants recorded in the e-Diary the number of nights per week in which they awakened with asthma, as determined by dividing the number of nights of awakening with asthma by the total number of nights and then multiplying by 7 (standardized to a 7-day period). The change from baseline in nocturnal awakenings was evaluated using the LDA model with repeated measurements of nocturnal awakenings, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Time Frame
The week before the first dose in Period III or V (Baseline) and the last week of Period III or V
Title
Change From Baseline in Morning (AM) Peak Expiratory Flow (PEF) at Week 4
Description
The change from baseline in AM PEF at Week 4 after treatment with MK-1029 + ML or placebo + ML was assessed in 97 participants. Participants performed triplicate AM PEF measurements in the morning upon rising. Participants entered all 3 measurements and the greatest AM PEF value was recorded by the e-Diary. Participants refrained from SABA use within the 4 hours prior to performing PEF measurements. The average AM PEF for an individual participant was calculated over the week-long assessment periods. The change from baseline in AM PEF was evaluated using the LDA model with repeated measurements of AM PEF, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Time Frame
The week before the first dose in Period III or V (Baseline) and the last week of Period III or V
Title
Change From Baseline in Evening (PM) PEF at Week 4
Description
The change from baseline in PM PEF at Week 4 after treatment with MK-1029 + ML or placebo + ML was assessed. Participants performed triplicate PM PEF measurements in the evening, immediately before study drug administration, at bedtime. Participants entered all 3 measurements and the greatest PM PEF value was recorded by the e-Diary. Participants refrained from SABA use within the 4 hours prior to performing PEF measurements. The average PM PEF for an individual participant was calculated over the week-long assessment periods. The change from baseline in PM PEF was evaluated using the LDA model with repeated measurements of PM PEF, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Time Frame
Baseline (Week 0 and Week 8), Last week of the 4-week treatment period
Title
Change From Baseline in Asthma Control Questionnaire (ACQ) Score at Week 4
Description
The change from baseline in the ACQ score at Week 4, after treatment, was assessed in 97 participants. Participants completed 6 items of the ACQ (i. e., ACQ-6) and provided the average of responses over the past week: 1) Frequency of nocturnal awakenings (0 = Never, 6 = Unable to sleep); 2) Symptom severity (0 = None, 6 = Very severe); 3) Activity limitations (0 = Not limited, 6 = Totally limited); 4) Breathlessness (0 = None, 6 = Very great deal); 5) Wheezing (0 = Not at all, 6 = All the time); 6) Daily SABA use (0 = None, 6 = More than 16 puffs on most days). The ACQ score ranges from 0 to 6 where a lower score indicates greater performance. The investigator reviewed the participant-completed ACQ-6 to ensure its completeness. The change from baseline in the ACQ score was evaluated using the LDA model with repeated measurements of the ACQ score, with treatment, visit, treatment-by-visit interaction, and period as fixed effects, and participant as random effect.
Time Frame
The week before the first dose in Period III or V (Baseline) and the last week of Period III or V
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
not pregnant or breastfeeding and does not plan to become pregnant for the duration of the study;
symptoms of persistent asthma for at least one year;
current use of asthma treatments: 1) "as-needed" inhaled SABAs (albuterol/salbutamol) and no asthma controller for at least 4 weeks prior to Screening Visit OR 2) stable dose of ICS, combination ICS/LABA and/or oral asthma controller(s) for at least 4 weeks prior to Screening Visit and able to tolerate discontinuing all controllers while receiving ML;
no history of smoking OR no smoking for at least 1 year, with a smoking history of no more than 10 pack-years;
able to maintain a constant day/night, awake/sleep cycle;
agrees to not change habitual consumption of beverages or foods containing caffeine throughout the study;
Body Mass Index (BMI) of 15 kg/m^2 to 40 kg/m^2.
Exclusion Criteria:
history of myocardial infarction, congestive heart failure, or uncontrolled cardiac arrhythmia within 3 months prior to Screening Visit;
hospitalized or hospitalization within 4 weeks prior to Screening Visit;
intention of moving or anticipation of missing any study visits;
any major surgical procedure(s) within 4 weeks prior to Screening Visit;
participation in a clinical trial involving an investigational drug within 4 weeks prior to Screening Visit;
current regular use or a recent past abuse (within past 5 years) of alcohol (>14 drinks/week) or illicit drugs;
donation of a unit of blood within 2 weeks prior to Screening Visit or intention of donating a unit of blood during the study;
evidence of another active pulmonary disorder such as bronchiectasis or COPD;
treatment in an emergency room for asthma within 4 weeks prior to Screening Visit or hospitalization for asthma within 2 months prior to Screening Visit;
respiratory tract infection which required treatment with antibiotics within 2 months prior to Screening Visit;
evidence of active sinus disease within 1 week prior to Screening Visit;
history of a psychiatric disorder, other than stable depression, within 3 months prior to Screening Visit;
history of human immunodeficiency virus (HIV);
hypersensitivity or intolerance to inhaled beta-agonists and/or leukotriene inhibitors or any of their ingredients, including lactose and galactose;
unstable disease of the ophthalmologic, neurological, hepatic, renal, connective tissue, genitourinary, gastrointestinal, cardiovascular or hematologic systems;
cancer (except for successfully treated basal and squamous cell carcinomas of the skin) or history of cancer within 5 years prior to Screening Visit;
uncontrolled hypertension.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Learn more about this trial
Study to Evaluate the Effectiveness and Safety of MK-1029 in the Treatment of Persistent Asthma That is Not Controlled With Montelukast (ML) in Adults (MK-1029-011)
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