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

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ClinicalTrials.gov Identifier: NCT02720081
Recruitment Status : Completed
First Posted : March 25, 2016
Results First Posted : August 28, 2018
Last Update Posted : September 27, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Asthma Drug: MK-1029 150 mg Drug: MK-1029 Matching-image Placebo Drug: Montelukast 10 mg Drug: Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 142 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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.
Actual Study Start Date : May 11, 2016
Actual Primary Completion Date : August 16, 2017
Actual Study Completion Date : September 6, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Montelukast

Arm Intervention/treatment
Experimental: MK-1029 150 mg + Montelukast 10 mg
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.
Drug: MK-1029 150 mg
150 mg tablet administered orally, once a day (QD), at bedtime

Drug: Montelukast 10 mg
10 mg tablet administered orally, QD, at bedtime
Other Names:
  • SINGULAIR®
  • Montelukast sodium

Drug: Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation
1 or 2 inhalations 4 times a day (QID) as needed (PRN) as a Rescue Medication

Placebo Comparator: MK-1029 Placebo + Montelukast 10 mg
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.
Drug: MK-1029 Matching-image Placebo
Matching-image placebo tablet administered orally, QD, at bedtime

Drug: Montelukast 10 mg
10 mg tablet administered orally, QD, at bedtime
Other Names:
  • SINGULAIR®
  • Montelukast sodium

Drug: Albuterol/Salbutamol 90 mcg - 100 mcg per inhalation
1 or 2 inhalations 4 times a day (QID) as needed (PRN) as a Rescue Medication




Primary Outcome Measures :
  1. Baseline Pre-dose Forced Expiratory Volume in One Second (FEV1) [ Time Frame: Before the first dose of study investigational product (Baseline) ]
    FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second.

  2. Average Change From Baseline in Pre-dose FEV1 at Week 4 and Week 6 [ Time Frame: Before the first dose (Baseline) and at the end of Weeks 4 and 6 of treatment ]
    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 :
  1. Percentage of Days With Worsening Asthma Average Over Weeks 3 to 6 [ Time Frame: Up to 4 weeks ]
    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.

  2. Percentage of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to 8 weeks ]
    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.

  3. Percentage of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to 6 weeks ]
    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.

  4. Change From Baseline in Alkaline Phosphatase (ALP) at Week 6 [ Time Frame: Baseline and 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.

  5. Change From Baseline in Alanine Aminotransferase (ALT) at Week 6 [ Time Frame: Baseline and 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.

  6. Change From Baseline in Aspartate Aminotransferase (AST) at Week 6 [ Time Frame: Baseline and 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.

  7. Change From Baseline in Bilirubin at Week 6 [ Time Frame: Baseline and 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.

  8. Change From Baseline in Eosinophil (Percent [%]) at Week 6 [ Time Frame: Baseline and 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.

  9. Change From Baseline in Neutrophil (%) at Week 6 [ Time Frame: Baseline and 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.

  10. Change From Baseline in Platelet Count at Week 6 [ Time Frame: Baseline and 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.

  11. Change From Baseline in White Blood Cell Count at Week 6 [ Time Frame: Baseline and 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.

  12. Change From Baseline in Hematocrit (%) at Week 6 [ Time Frame: Baseline and 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.

  13. Change From Baseline in Systolic Blood Pressure at Week 2 [ Time Frame: Baseline and 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.

  14. Change From Baseline in Systolic Blood Pressure at Week 4 [ Time Frame: Baseline and 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.

  15. Change From Baseline in Systolic Blood Pressure at Week 6 [ Time Frame: Baseline and 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.

  16. Change From Baseline in Diastolic Blood Pressure at Week 2 [ Time Frame: Baseline and 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.

  17. Change From Baseline in Diastolic Blood Pressure at Week 4 [ Time Frame: Baseline and 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.

  18. Change From Baseline in Diastolic Blood Pressure at Week 6 [ Time Frame: Baseline and 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.

  19. Change From Baseline in Heart Rate at Week 2 [ Time Frame: Baseline and 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.

  20. Change From Baseline in Heart Rate at Week 4 [ Time Frame: Baseline and 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.

  21. Change From Baseline in Heart Rate at Week 6 [ Time Frame: Baseline and 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.

  22. Change From Baseline in Respiratory Rate at Week 2 [ Time Frame: Baseline and 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.

  23. Change From Baseline in Respiratory Rate at Week 4 [ Time Frame: Baseline and 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.

  24. Change From Baseline in Respiratory Rate at Week 6 [ Time Frame: Baseline and 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02720081


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme Corp.:

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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02720081     History of Changes
Other Study ID Numbers: 1029-015
2015-005054-36 ( EudraCT Number )
MK-1029-015 ( Other Identifier: Merck Registration Number )
163313 ( Registry Identifier: JAPIC-CTI )
First Posted: March 25, 2016    Key Record Dates
Results First Posted: August 28, 2018
Last Update Posted: September 27, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Albuterol
Montelukast
Anti-Asthmatic Agents
Respiratory System Agents
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents