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Study of MK-1029 in Participants With Persistent Asthma That Cannot Be Controlled With Montelukast (MK-1029-015)

Primary Purpose

Asthma

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
MK-1029 150 mg
MK-1029 Matching-image Placebo
Montelukast 10 mg
Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Symptoms of persistent asthma for at least one year
  • History of asthma treatments including "as-needed" inhaled short-acting beta-agonists (albuterol/salbutamol); stable doses of inhaled corticosteroids (ICS), combination ICS/long-acting (inhaled) Beta2-adrenergic agonist (LABA) and/or oral asthma controller(s)
  • Must be able to discontinue or taper asthma controlling medications while receiving Montelukast
  • No history of smoking or no smoking for at least 1 year, with a smoking history of no more than 10 pack-years
  • Body Mass Index (BMI) of 15 kg/m^2 to 40 kg/m^2.
  • Females must not be pregnant (negative serum human chorionic gonadotropin test) or breastfeeding and must not plan to become pregnant for the duration of the study, including the post-treatment follow-up period
  • Women and male participants of reproductive potential must agree to use adequate contraception for the duration of the study

Exclusion Criteria:

  • Evidence of another active pulmonary disorder such as bronchiectasis or chronic obstructive pulmonary disease (COPD)
  • Unable to perform acceptable, repeatable spirometry
  • History of myocardial infarction, congestive heart failure, or uncontrolled cardiac arrhythmia within 3 months of screening visit
  • Major surgical procedure(s) within 4 weeks of screening visit
  • Blood donation within 2 weeks of screening visit
  • Treatment in an emergency room for asthma (within 4 weeks) or hospitalization for asthma or respiratory condition within 2 months of screening visit
  • Evidence of active sinus disease within 2 weeks of screening visit
  • Upper respiratory infection (viral or bacterial) within 1 month of screening visit
  • History of a psychiatric disorder within 3 months of screening visit
  • History of human immunodeficiency virus (HIV)
  • Unstable disease of the ophthalmologic, neurological, hepatic, renal, connective tissue, genitourinary, gastrointestinal, cardiovascular or hematologic systems
  • History of cancer (except for successfully treated basal and squamous cell carcinomas of the skin) within 5 years of screening visit
  • Uncontrolled hypertension
  • Participation in a clinical trial involving an investigational drug within 4 weeks of screening visit
  • Hypersensitivity or intolerance to inhaled beta-agonists and/or leukotriene inhibitors or any of their ingredients, including lactose and galactose
  • Known sensitivity to or has not had previous exposure to aspirin or non-steroidal anti-inflammatory drugs

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    MK-1029 150 mg + Montelukast 10 mg

    MK-1029 Placebo + Montelukast 10 mg

    Arm Description

    Participants receive single-blind MK-1029 Matching-image Placebo + open-label Montelukast 10 mg for a 2 to 4 week run-in period while discontinuing or tapering off asthma controller medications. Participants receive double-blind MK-1029 150 mg + Montelukast 10 mg for 6 weeks in the treatment period. Participants can use rescue medication during both periods as needed.

    Participants receive single-blind MK-1029 Matching-image Placebo + open-label Montelukast 10 mg for a 2 to 4 week run-in period while discontinuing or tapering off asthma controller medications. Participants receive double-blind MK-1029 Matching-image Placebo + Montelukast 10 mg for 6 weeks in the treatment period. Participants can use rescue medication during both periods as needed.

    Outcomes

    Primary Outcome Measures

    Baseline Pre-dose Forced Expiratory Volume in One Second (FEV1)
    FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second.
    Average Change From Baseline in Pre-dose FEV1 at Week 4 and Week 6
    FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. Data presented represents the average change from baseline at Week 4 and Week 6.

    Secondary Outcome Measures

    Percentage of Days With Worsening Asthma Average Over Weeks 3 to 6
    A day with worsening asthma was defined as any day during which any of the following occurred: a decrease from baseline in morning (AM) peak expiratory flow (PEF) of more than 20%; AM PEF less than 180 liters/minute (L/min); an increase in β-agonist 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%; overnight asthma symptom of: Awake "all night"; an asthma attack, as defined by any day when one or more of the following events due to asthma has occurred: corticosteroid use (systemic); unscheduled visit to the doctor or urgent care clinic; unscheduled visit to the emergency department; and/or hospitalization. Participants needed at least 80% of days with a complete diary during Weeks 3 to 6. A diary is considered complete if none of the above 6 components used to determine asthma worsening are missing.
    Percentage of Participants Who Experienced an Adverse Event (AE)
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
    Percentage of Participants Who Discontinued Study Drug Due to an AE
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
    Change From Baseline in Alkaline Phosphatase (ALP) at Week 6
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Alanine Aminotransferase (ALT) at Week 6
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Aspartate Aminotransferase (AST) at Week 6
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Bilirubin at Week 6
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Eosinophil (Percent [%]) at Week 6
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Neutrophil (%) at Week 6
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Platelet Count at Week 6
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in White Blood Cell Count at Week 6
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Hematocrit (%) at Week 6
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Systolic Blood Pressure at Week 2
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Systolic Blood Pressure at Week 4
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Systolic Blood Pressure at Week 6
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Diastolic Blood Pressure at Week 2
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Diastolic Blood Pressure at Week 4
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Diastolic Blood Pressure at Week 6
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Heart Rate at Week 2
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Heart Rate at Week 4
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Heart Rate at Week 6
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Respiratory Rate at Week 2
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Respiratory Rate at Week 4
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Change From Baseline in Respiratory Rate at Week 6
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.

    Full Information

    First Posted
    March 22, 2016
    Last Updated
    August 30, 2018
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT02720081
    Brief Title
    Study of MK-1029 in Participants With Persistent Asthma That Cannot Be Controlled With Montelukast (MK-1029-015)
    Official Title
    A Phase-II, Randomized, Placebo-Controlled, Parallel-Group Clinical Trial to Study the Efficacy and Safety of MK-1029 in Adult Subjects With Persistent Asthma That is Uncontrolled While Receiving Montelukast.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2018
    Overall Recruitment Status
    Completed
    Study Start Date
    May 11, 2016 (Actual)
    Primary Completion Date
    August 16, 2017 (Actual)
    Study Completion Date
    September 6, 2017 (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 trial is to compare the safety, tolerability, and efficacy of adding MK-1029 to montelukast in adults with persistent asthma that is uncontrolled while receiving montelukast alone. Participants will have a specific genetic marker for clinical efficacy of MK-1029. The primary hypothesis is that when added to montelukast, treatment with MK-1029 is superior to placebo, as demonstrated by an increase in forced expiratory volume in one second (FEV1), measured as the average change from baseline at the end of Week 4 and Week 6 of treatment.

    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
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    142 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    MK-1029 150 mg + Montelukast 10 mg
    Arm Type
    Experimental
    Arm Description
    Participants receive single-blind MK-1029 Matching-image Placebo + open-label Montelukast 10 mg for a 2 to 4 week run-in period while discontinuing or tapering off asthma controller medications. Participants receive double-blind MK-1029 150 mg + Montelukast 10 mg for 6 weeks in the treatment period. Participants can use rescue medication during both periods as needed.
    Arm Title
    MK-1029 Placebo + Montelukast 10 mg
    Arm Type
    Placebo Comparator
    Arm Description
    Participants receive single-blind MK-1029 Matching-image Placebo + open-label Montelukast 10 mg for a 2 to 4 week run-in period while discontinuing or tapering off asthma controller medications. Participants receive double-blind MK-1029 Matching-image Placebo + Montelukast 10 mg for 6 weeks in the treatment period. Participants can use rescue medication during both periods as needed.
    Intervention Type
    Drug
    Intervention Name(s)
    MK-1029 150 mg
    Intervention Description
    150 mg tablet administered orally, once a day (QD), at bedtime
    Intervention Type
    Drug
    Intervention Name(s)
    MK-1029 Matching-image Placebo
    Intervention Description
    Matching-image placebo tablet administered orally, QD, at bedtime
    Intervention Type
    Drug
    Intervention Name(s)
    Montelukast 10 mg
    Other Intervention Name(s)
    SINGULAIR®, Montelukast sodium
    Intervention Description
    10 mg tablet administered orally, QD, at bedtime
    Intervention Type
    Drug
    Intervention Name(s)
    Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation
    Intervention Description
    1 or 2 inhalations 4 times a day (QID) as needed (PRN) as a Rescue Medication
    Primary Outcome Measure Information:
    Title
    Baseline Pre-dose Forced Expiratory Volume in One Second (FEV1)
    Description
    FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second.
    Time Frame
    Before the first dose of study investigational product (Baseline)
    Title
    Average Change From Baseline in Pre-dose FEV1 at Week 4 and Week 6
    Description
    FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. Data presented represents the average change from baseline at Week 4 and Week 6.
    Time Frame
    Before the first dose (Baseline) and at the end of Weeks 4 and 6 of treatment
    Secondary Outcome Measure Information:
    Title
    Percentage of Days With Worsening Asthma Average Over Weeks 3 to 6
    Description
    A day with worsening asthma was defined as any day during which any of the following occurred: a decrease from baseline in morning (AM) peak expiratory flow (PEF) of more than 20%; AM PEF less than 180 liters/minute (L/min); an increase in β-agonist 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%; overnight asthma symptom of: Awake "all night"; an asthma attack, as defined by any day when one or more of the following events due to asthma has occurred: corticosteroid use (systemic); unscheduled visit to the doctor or urgent care clinic; unscheduled visit to the emergency department; and/or hospitalization. Participants needed at least 80% of days with a complete diary during Weeks 3 to 6. A diary is considered complete if none of the above 6 components used to determine asthma worsening are missing.
    Time Frame
    Up to 4 weeks
    Title
    Percentage of Participants Who Experienced an Adverse Event (AE)
    Description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
    Time Frame
    Up to 8 weeks
    Title
    Percentage of Participants Who Discontinued Study Drug Due to an AE
    Description
    An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
    Time Frame
    Up to 6 weeks
    Title
    Change From Baseline in Alkaline Phosphatase (ALP) at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Alanine Aminotransferase (ALT) at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Aspartate Aminotransferase (AST) at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Bilirubin at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Eosinophil (Percent [%]) at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Neutrophil (%) at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Platelet Count at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in White Blood Cell Count at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Hematocrit (%) at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement is not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Systolic Blood Pressure at Week 2
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 2
    Title
    Change From Baseline in Systolic Blood Pressure at Week 4
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline in Systolic Blood Pressure at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Diastolic Blood Pressure at Week 2
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 2
    Title
    Change From Baseline in Diastolic Blood Pressure at Week 4
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline in Diastolic Blood Pressure at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Heart Rate at Week 2
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 2
    Title
    Change From Baseline in Heart Rate at Week 4
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline in Heart Rate at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6
    Title
    Change From Baseline in Respiratory Rate at Week 2
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 2
    Title
    Change From Baseline in Respiratory Rate at Week 4
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 4
    Title
    Change From Baseline in Respiratory Rate at Week 6
    Description
    Baseline was defined at Week 0. If Week 0 measurement was not available, the last non-missing value before treatment was used as Baseline.
    Time Frame
    Baseline and Week 6

    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: Symptoms of persistent asthma for at least one year History of asthma treatments including "as-needed" inhaled short-acting beta-agonists (albuterol/salbutamol); stable doses of inhaled corticosteroids (ICS), combination ICS/long-acting (inhaled) Beta2-adrenergic agonist (LABA) and/or oral asthma controller(s) Must be able to discontinue or taper asthma controlling medications while receiving Montelukast No history of smoking or no smoking for at least 1 year, with a smoking history of no more than 10 pack-years Body Mass Index (BMI) of 15 kg/m^2 to 40 kg/m^2. Females must not be pregnant (negative serum human chorionic gonadotropin test) or breastfeeding and must not plan to become pregnant for the duration of the study, including the post-treatment follow-up period Women and male participants of reproductive potential must agree to use adequate contraception for the duration of the study Exclusion Criteria: Evidence of another active pulmonary disorder such as bronchiectasis or chronic obstructive pulmonary disease (COPD) Unable to perform acceptable, repeatable spirometry History of myocardial infarction, congestive heart failure, or uncontrolled cardiac arrhythmia within 3 months of screening visit Major surgical procedure(s) within 4 weeks of screening visit Blood donation within 2 weeks of screening visit Treatment in an emergency room for asthma (within 4 weeks) or hospitalization for asthma or respiratory condition within 2 months of screening visit Evidence of active sinus disease within 2 weeks of screening visit Upper respiratory infection (viral or bacterial) within 1 month of screening visit History of a psychiatric disorder within 3 months of screening visit History of human immunodeficiency virus (HIV) Unstable disease of the ophthalmologic, neurological, hepatic, renal, connective tissue, genitourinary, gastrointestinal, cardiovascular or hematologic systems History of cancer (except for successfully treated basal and squamous cell carcinomas of the skin) within 5 years of screening visit Uncontrolled hypertension Participation in a clinical trial involving an investigational drug within 4 weeks of screening visit Hypersensitivity or intolerance to inhaled beta-agonists and/or leukotriene inhibitors or any of their ingredients, including lactose and galactose Known sensitivity to or has not had previous exposure to aspirin or non-steroidal anti-inflammatory drugs
    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
    https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php

    Learn more about this trial

    Study of MK-1029 in Participants With Persistent Asthma That Cannot Be Controlled With Montelukast (MK-1029-015)

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