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CompletedNCT03449147Updated Sep 2, 2021Results posted

A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-030)

A Phase 3 interventional study of Placebo and Gefapixant 15 mg BID in Chronic Cough, sponsored by Merck Sharp & Dohme LLC. Completed at 171 sites in 20 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-02.

Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,317
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The primary objectives of this study are to evaluate the efficacy of gefapixant (MK-7264) in reducing cough frequency as measured over a 24-hour period, and to determine the safety and tolerability of gefapixant. The primary hypothesis is that at least one dose of gefapixant is superior to placebo in reducing coughs per hour (over 24 hours) at Week 24.

Read the detailed description

This study will have a main 24-week treatment period and a 28-week extension period of treatment (total treatment period of 52 weeks). Participants at selected sites and countries who complete the main and extension study periods may consent to participate in an observational, 12-week, Off-treatment Durability Study Period. Any assessments conducted in the observational period will be exploratory.

02

Conditions studied

  • Chronic Cough
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Chest radiograph or computed tomography scan of the thorax (within 5 years of Screening/Visit 1 and after the onset of chronic cough) not demonstrating any abnormality considered to be significantly contributing to the chronic cough or any other clinically significant lung disease in the opinion of the principal investigator or the sub-investigator
  • Has had chronic cough for at least 1 year with a diagnosis of refractory chronic cough or unexplained chronic cough
  • Is a female who is not pregnant, not breastfeeding, not of childbearing potential, or agrees to follow contraceptive guidance
  • Provides written informed consent and is willing and able to comply with the study protocol (including use of the digital cough recording device and completion of study questionnaires)

Exclusion criteria

Exclusion Criteria:

  • Is a current smoker or has given up smoking within 12 months of Screening, or is a former smoker with greater than 20 pack-years
  • Has a history of respiratory tract infection or recent clinically significant change in pulmonary status
  • Has a history of chronic bronchitis
  • Is currently taking an angiotensin converting enzyme inhibitor (ACEI), or has used an ACEI within 3 months of Screening
  • Has an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m\^2 at Screening OR an eGFR ≥30 mL/min/1.73 m\^2 and \<50 mL/min/1.73 m\^2 at Screening with unstable renal function
  • Has a history of malignancy ≤5 years
  • Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence
  • Has a history of anaphylaxis or cutaneous adverse drug reaction (with or without systemic symptoms) to sulfonamide antibiotics or other sulfonamide-containing drugs
  • Has a known allergy/sensitivity or contraindication to gefapixant
  • Has donated or lost ≥1 unit of blood within 8 weeks prior to the first dose of gefapixant
  • Has previously received gefapixant
  • Currently participating in or has participated in an interventional clinical study within 30 days of screening
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
1,317 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Participants will receive a matching placebo tablet BID during the 24-week main study period and the 28-week extension period.

    Drug: Placebo

  • Experimental
    Gefapixant 15 mg BID

    Participants will receive a gefapixant 15 mg tablet BID and placebo tablet to match gefapixant 45 mg BID during the 24-week main study period and the 28-week extension period.

    Drug: Placebo · Drug: Gefapixant 15 mg BID

  • Experimental
    Gefapixant 45 mg BID

    Participants will receive a gefapixant 45 mg tablet BID and placebo tablet to match gefapixant 15 mg BID during the 24-week main study period and during the 28-week extension period.

    Drug: Placebo · Drug: Gefapixant 45 mg BID

Interventions

  • DrugPlacebo

    Placebo tablet administered orally BID

  • DrugGefapixant 15 mg BID

    Gefapixant 15 mg tablet administered orally BID

    Also known as: MK-7264

  • DrugGefapixant 45 mg BID

    Gefapixant 45 mg tablet administered orally BID

    Also known as: MK-7264

05

What researchers measure

Primary outcomes

  1. Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline

    24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough data to determine geometric mean (GM) 24-hour coughs per hour at baseline and week 24. The GMR (Week 24 GM 24-hour coughs per hour divided by Baseline GM 24-hour coughs per hour) is reported.

    Time frame: Baseline, Week 24

  2. Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

    Time frame: Up to 54 Weeks

  3. Number of Participants Who Discontinued a Study Drug Due to an AE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

    Time frame: Up to 52 weeks

Secondary outcomes

  1. Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline

    Awake coughs per hour was defined as the average hourly cough frequency while the participant is awake, based on a 24-hour interval of sound recordings using a digital recording device (cough monitor). ANCOVA model was applied to log-transformed cough data to determine GM of awake coughs per hour at baseline and week 24. The GMR (Week 24 GM awake coughs per hour divided by Baseline GM awake coughs per hour) is reported.

    Time frame: Baseline, Week 24

  2. Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24

    The 19-item LCQ assessed the impact of chronic cough in three health-related quality of life (HRQoL) domains (physical, social and psychological). The LCQ is calculated as a mean score for each domain ranging from 1 to 7, with a total score ranging from 3 to 21. Higher scores indicate better HRQoL. A clinically meaningful improvement from baseline in HRQoL was defined as ≥1.3-point increase in the LCQ total score at Week 24. The percentage of participants (logistic regression model-based) with a ≥1.3-point increase in the LCQ total score at Week 24 is presented.

    Time frame: Baseline, Week 24

  3. Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24

    24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A clinically meaningful improvement from baseline is defined as a ≤-30% change (≥30% reduction) in 24-hour coughs per hour at week 24. The percentage of participants (logistic regression model-based) with a ≤ -30% change from baseline in 24-hour coughs per hour at Week 24 (≥30% reduction from baseline) is presented.

    Time frame: Baseline, Week 24

  4. Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24

    The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-1.3 point change from baseline in CSD at Week 24 (or ≥1.3 point reduction from baseline) is reported.

    Time frame: Baseline, Week 24

  5. Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24

    The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-2.7 point change from baseline in CSD at Week 24 (or ≥2.7 point reduction from baseline) is reported.

    Time frame: Baseline, Week 24

  6. Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24

    The VAS is a single-item questionnaire with the response on a 100- point scale ranging from 0 ("No Cough") to 100 ("Extremely Severe Cough"). Mean weekly VAS score was defined as the average of the VAS scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-30 mm change from baseline in cough severity VAS score at Week 24 is reported.

    Time frame: Baseline, Week 24

06

Results

Posted Sep 2, 2021

Participant flow

52-week Treatment Period
Participant flow — 52-week Treatment Period
MilestonePlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Started436442439
Completed382368355
Not completed547484
Withdrew: Death010
Withdrew: Lost to follow-up625
Withdrew: Other012
Withdrew: Physician decision103
Withdrew: Screen failure120
Withdrew: Withdrawal by subject466874
12-Week Off-Treatment Durability Period
Participant flow — 12-Week Off-Treatment Durability Period
MilestonePlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Started483737
Completed473637
Not completed110
Withdrew: Withdrawal by subject100
Withdrew: Other010

Outcome measures

PrimaryModel-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline

24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough data to determine geometric mean (GM) 24-hour coughs per hour at baseline and week 24. The GMR (Week 24 GM 24-hour coughs per hour divided by Baseline GM 24-hour coughs per hour) is reported.

Time frame:
Baseline, Week 24
Reported as:
Geometric mean · Ratio
Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline
RatioPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline0.43 (0.39 to 0.48)0.43 (0.38 to 0.47)0.37 (0.33 to 0.41)
Statistical analysis
  • Placebo vs Gefapixant 15 mg BID · ANCOVA · p = 0.875 (Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.) · Estimated relative reduction (%): -1.14 · 95% CI -14.27 to 14.02
  • Placebo vs Gefapixant 45 mg BID · ANCOVA · p = 0.031 (Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.) · Estimated relative reduction (%): -14.64 · 95% CI -26.07 to -1.43
PrimaryNumber of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Time frame:
Up to 54 Weeks
Reported as:
Count of participants · Participants
Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up
ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up349373399
PrimaryNumber of Participants Who Discontinued a Study Drug Due to an AE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Time frame:
Up to 52 weeks
Reported as:
Count of participants · Participants
Number of Participants Who Discontinued a Study Drug Due to an AE
ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Number of Participants Who Discontinued a Study Drug Due to an AE2540100
SecondaryModel-Based GMR of Awake Coughs Per Hour at Week 24/Baseline

Awake coughs per hour was defined as the average hourly cough frequency while the participant is awake, based on a 24-hour interval of sound recordings using a digital recording device (cough monitor). ANCOVA model was applied to log-transformed cough data to determine GM of awake coughs per hour at baseline and week 24. The GMR (Week 24 GM awake coughs per hour divided by Baseline GM awake coughs per hour) is reported.

Time frame:
Baseline, Week 24
Reported as:
Geometric mean · Ratio
Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline
RatioPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline0.42 (0.38 to 0.47)0.41 (0.37 to 0.46)0.36 (0.32 to 0.40)
Statistical analysis
  • Placebo vs Gefapixant 15 mg BID · ANCOVA · p = 0.677 (Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.) · Estimated relative reduction (%): -3.03 · 95% CI -16.14 to 12.12
  • Placebo vs Gefapixant 45 mg BID · ANCOVA · p = 0.022 (Comparison based on a longitudinal ANCOVA model that included treatment, visit, treatment-by-visit interaction, gender, region, log-transformed baseline value, and log-transformed baseline value-by-visit as covariates.) · Estimated relative reduction (%): -15.79 · 95% CI -27.27 to -2.50
SecondaryPercentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24

The 19-item LCQ assessed the impact of chronic cough in three health-related quality of life (HRQoL) domains (physical, social and psychological). The LCQ is calculated as a mean score for each domain ranging from 1 to 7, with a total score ranging from 3 to 21. Higher scores indicate better HRQoL. A clinically meaningful improvement from baseline in HRQoL was defined as ≥1.3-point increase in the LCQ total score at Week 24. The percentage of participants (logistic regression model-based) with a ≥1.3-point increase in the LCQ total score at Week 24 is presented.

Time frame:
Baseline, Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24
Percentage of ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg
Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 2470.175.976.8
Statistical analysis
  • Placebo vs Gefapixant 15 mg BID · Regression, Logistic · p = 0.077 (Comparison based on logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline LCQ total score, and the interaction of baseline LCQ total score by visit as covariates.) · Odds ratio (or): 1.34 · 95% CI 0.97 to 1.85
  • Placebo vs Gefapixant 45 mg · Regression, Logistic · p = 0.040 (Comparison based on logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline LCQ total score, and the interaction of baseline LCQ total score by visit as covariates.) · Odds ratio (or): 1.41 · 95% CI 1.02 to 1.96
SecondaryPercentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24

24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A clinically meaningful improvement from baseline is defined as a ≤-30% change (≥30% reduction) in 24-hour coughs per hour at week 24. The percentage of participants (logistic regression model-based) with a ≤ -30% change from baseline in 24-hour coughs per hour at Week 24 (≥30% reduction from baseline) is presented.

Time frame:
Baseline, Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24
Percentage of ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 2466.967.472.9
Statistical analysis
  • Placebo vs Gefapixant 15 mg BID · Regression, Logistic · p = 0.872 (Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline 24-hour coughs per hour and the interaction of baseline 24-hour coughs per hour as covariates.) · Odds ratio (or): 1.03 · 95% CI 0.75 to 1.40
  • Placebo vs Gefapixant 45 mg BID · Regression, Logistic · p = 0.082 (Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline 24-hour coughs per hour and the interaction of baseline 24-hour coughs per hour as covariates.) · Odds ratio (or): 1.33 · 95% CI 0.96 to 1.83
SecondaryPercentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24

The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-1.3 point change from baseline in CSD at Week 24 (or ≥1.3 point reduction from baseline) is reported.

Time frame:
Baseline, Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24
Percentage of ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg
Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 2469.174.877.1
Statistical analysis
  • Placebo vs Gefapixant 15 mg BID · Odds ratio (or): 1.33 · 95% CI 0.96 to 1.83
  • Placebo vs Gefapixant 45 mg · Odds ratio (or): 1.50 · 95% CI 1.08 to 2.09
SecondaryPercentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24

The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-2.7 point change from baseline in CSD at Week 24 (or ≥2.7 point reduction from baseline) is reported.

Time frame:
Baseline, Week 24
Reported as:
Number · Percentage of Participants
Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24
Percentage of ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg
Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 2441.046.655.2
Statistical analysis
  • Placebo vs Gefapixant 15 mg BID · Odds ratio (or): 1.25 · 95% CI 0.93 to 1.69
  • Placebo vs Gefapixant 45 mg · Odds ratio (or): 1.77 · 95% CI 1.31 to 2.39
SecondaryPercentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24

The VAS is a single-item questionnaire with the response on a 100- point scale ranging from 0 ("No Cough") to 100 ("Extremely Severe Cough"). Mean weekly VAS score was defined as the average of the VAS scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-30 mm change from baseline in cough severity VAS score at Week 24 is reported.

Time frame:
Baseline, Week 24
Reported as:
Number · Percentage of participants
Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24
Percentage of participantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg
Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 2440.951.453.3
Statistical analysis
  • Placebo vs Gefapixant 15 mg BID · Odds ratio (or): 1.53 · 95% CI 1.14 to 2.05
  • Placebo vs Gefapixant 45 mg · Odds ratio (or): 1.65 · 95% CI 1.23 to 2.22

Adverse events

Collected over On-Treatment Period: Up to Week 54; Off-Treatment (Off-Tx) Period: From Week 52 through Week 64 (approximately 12 weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/433 (0%)25/432 (5.8%)248/432 (57.4%)
Gefapixant 15 mg BID1/444 (0.2%)24/442 (5.4%)290/442 (65.6%)
Gefapixant 45 mg BID0/440 (0%)25/440 (5.7%)359/440 (81.6%)
Placebo: Off Tx0/48 (0%)0/48 (0%)6/48 (12.5%)
Gefapixant 15 mg BID: Off Tx0/37 (0%)0/37 (0%)3/37 (8.1%)
Gefapixant 45 mg BID: Off Tx0/37 (0%)1/37 (2.7%)1/37 (2.7%)
Most frequent serious events
Showing 10 of 77
Most frequent serious events
EventPlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDPlacebo: Off TxGefapixant 15 mg BID: Off TxGefapixant 45 mg BID: Off Tx
ArrhythmiaCardiac disorders0/4320/4420/4400/480/371/37
PneumoniaInfections and infestations0/4323/4421/4400/480/370/37
GastritisGastrointestinal disorders2/4320/4420/4400/480/370/37
UrosepsisInfections and infestations2/4320/4420/4400/480/370/37
Laryngeal stenosisRespiratory, thoracic and mediastinal disorders2/4320/4420/4400/480/370/37
InfluenzaInfections and infestations0/4322/4420/4400/480/370/37
Myocardial infarctionCardiac disorders1/4320/4420/4400/480/370/37
PyrexiaGeneral disorders1/4320/4420/4400/480/370/37
BronchitisInfections and infestations1/4320/4420/4400/480/370/37
COVID-19 pneumoniaInfections and infestations1/4320/4420/4400/480/370/37
Most frequent other events
Showing 10 of 19
Most frequent other events
EventPlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDPlacebo: Off TxGefapixant 15 mg BID: Off TxGefapixant 45 mg BID: Off Tx
DysgeusiaNervous system disorders28/43256/442193/4400/480/370/37
NasopharyngitisInfections and infestations70/43293/44270/4402/480/370/37
HeadacheNervous system disorders67/43274/44270/4401/480/370/37
AgeusiaNervous system disorders6/43213/44267/4400/480/370/37
HypogeusiaNervous system disorders3/43217/44260/4400/480/370/37
NauseaGastrointestinal disorders32/43226/44247/4400/480/370/37
Upper respiratory tract infectionInfections and infestations26/43238/44230/4400/480/370/37
Taste disorderNervous system disorders1/4328/44237/4400/480/370/37
AsthmaRespiratory, thoracic and mediastinal disorders11/43213/44219/4401/483/371/37
InfluenzaInfections and infestations35/43229/44224/4400/480/370/37

Baseline characteristics

Age, Continuous
Age, Continuous(Years)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
Mean58.4 ± 12.558.4 ± 11.357.8 ± 12.458.2 ± 12.1
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
Female326331329986
Male110111110331
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
Hispanic or Latino859389267
Not Hispanic or Latino3483473441039
Unknown or Not Reported32611
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
American Indian or Alaska Native20282472
Asian15141544
Native Hawaiian or Other Pacific Islander4239
Black or African American591428
White3563583461060
More than one race363137104
Unknown or Not Reported0000
Baseline 24-Hour Coughs Per Hour
Baseline 24-Hour Coughs Per Hour(Coughs/Hour)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
Mean27.45 ± 24.4426.82 ± 21.2526.84 ± 27.0427.04 ± 24.35
07

Study locations

171 sites
  • Phoenix Medical Group ( Site 0022)
    Peoria, Arizona 85381, United States
  • Pulmonary Associates, PA ( Site 0063)
    Phoenix, Arizona 85006, United States
  • Clinical Research Consortium ( Site 0088)
    Tempe, Arizona 85283, United States
  • Allergy & Asthma Associates of SCV Research Center ( Site 0064)
    San Jose, California 95117, United States
  • Lenus Research & Medical Group Llc ( Site 0075)
    Sweetwater, Florida 33172, United States
  • Atlanta Allergy & Asthma Clinic PA ( Site 0029)
    Stockbridge, Georgia 30281, United States
  • Rush University Medical Center ( Site 0103)
    Chicago, Illinois 60612, United States
  • Healthcare Research Network LLC ( Site 0093)
    Flossmoor, Illinois 60422, United States
  • Abraham Research, PLLC ( Site 0107)
    Fort Mitchell, Kentucky 41017, United States
  • Paul A. Shapero, MD ( Site 0104)
    Bangor, Maine 04401, United States
  • Bethesda Allergy Asthma and Research Center LLC ( Site 0019)
    Bethesda, Maryland 20814, United States
  • Respiratory Medicine Research Institute of Michigan, PLC ( Site 0034)
    Ypsilanti, Michigan 48197, United States
  • Minnesota Lung Center ( Site 0108)
    Edina, Minnesota 55435, United States
  • Mayo Clinic - Rochester ( Site 0006)
    Rochester, Minnesota 55905, United States
  • Minnesota Lung Center ( Site 0041)
    Woodbury, Minnesota 55125, United States
  • The Lung Research Center ( Site 0072)
    Chesterfield, Missouri 63017, United States
  • University of Missouri ENT & Allergy Center ( Site 0066)
    Columbia, Missouri 65201, United States
  • CHI Health Creighton University Medical Center ( Site 0024)
    Omaha, Nebraska 68134, United States
  • Clinical Research Consortium ( Site 0050)
    Las Vegas, Nevada 89109, United States
  • Atlantic Research Center LLC ( Site 0012)
    Ocean City, New Jersey 07712, United States
  • Albuquerque Clinical Trials ( Site 0039)
    Albuquerque, New Mexico 87102, United States
  • Montefiore Medical Center ( Site 0098)
    Bronx, New York 10461, United States
  • Wake Research Associates, LLC ( Site 0058)
    Raleigh, North Carolina 27612, United States
  • Remington-Davis, Inc. ( Site 0082)
    Columbus, Ohio 43215, United States
  • Clinical Research Institute of Southern Oregon, PC ( Site 0099)
    Medford, Oregon 97504, United States
  • Allergy Associates Research Center ( Site 0026)
    Portland, Oregon 97202, United States
  • AAPRI Clinical Research Institute ( Site 0001)
    Warwick, Rhode Island 02886, United States
  • Lowcountry Lung & Critical Care, PA ( Site 0045)
    Charleston, South Carolina 29406, United States
  • Allergic Disease and Asthma Center ( Site 0043)
    Greenville, South Carolina 29607, United States
  • Clinical Research of Rock Hill ( Site 0079)
    Rock Hill, South Carolina 29732, United States
  • Clinical Research Partners, LLC. ( Site 0080)
    Richmond, Virginia 23235, United States
  • Bellingham Asthma & Allergy ( Site 0076)
    Bellingham, Washington 98225, United States
  • Marycliff Clinical Research ( Site 0062)
    Spokane, Washington 99202, United States
  • Multicare Health System ( Site 0018)
    Tacoma, Washington 98405, United States
  • Australian Clinical Research Network ( Site 0201)
    Maroubra, New South Wales 2035, Australia
  • Holdsworth House Medical Practice ( Site 0206)
    Sydney, New South Wales 2010, Australia
  • Royal Adelaide Hospital [Adelaide, Australia] ( Site 0214)
    Adelaide, South Australia 5000, Australia
  • Trialswest ( Site 0208)
    Murdoch, 6150, Australia
  • Hamilton Medical Research Group ( Site 0510)
    Hamilton, Ontario L8M 1K7, Canada
  • Recherche GCP Research ( Site 0500)
    Montreal, Quebec H1M 1B1, Canada
  • Q & T Research Sherbrooke Inc. ( Site 0512)
    Sherbrooke, Quebec J1J 2G2, Canada
  • Clinique de Pneumologie et du Sommeil de Lanaudiere- CPSL ( Site 0516)
    St-Charles-Borromee, Quebec J6E 2B4, Canada
  • CIC Mauricie Inc. ( Site 0503)
    Trois-Rivieres, Quebec G8T 7A1, Canada
  • Diex Recherche Victoriaville Inc. ( Site 0514)
    Victoriaville, Quebec G6P 6P6, Canada
  • Diex Recherche Quebec Inc ( Site 0515)
    Quebec, G1N 4V3, Canada
  • Clinique Specialisee en Allergie de la Capitale - CSAC ( Site 0504)
    Quebec, G1V 4W2, Canada
  • The First Affiliated Hospital of Fujian Medical University ( Site 5017)
    Fuzhou, Fujian 350005, China
  • The First Affiliated Hospital of Guangzhou Medical University ( Site 5000)
    Guangzhou, Guangdong 510120, China
  • Inner Mongolia Autonomous Region Hospital ( Site 5018)
    Hohhot, Inner Mongolia 010017, China
  • The First Affiliated Hospital of Nanchang University ( Site 5012)
    Nanchang, Jiangxi 330006, China
  • ShengJing Hospital of China Medical University ( Site 5024)
    Shenyang, Liaoning 110004, China
  • Shanghai General Hospital ( Site 5010)
    Shanghai, Shanghai 200080, China
  • The First Affiliated Hospital of Zhejiang University ( Site 5014)
    Hangzhou, Zhejiang 310003, China
  • Peking University Third Hospital ( Site 5005)
    Beijing, 100191, China
  • Fundacion Centro de Investigacion Clinica CIC ( Site 0603)
    Medellin, Antioquia 050021, Colombia
  • Hospital Pablo Tobon Uribe ( Site 0600)
    Medellin, Antioquia 050034, Colombia
  • Universidad Pontificia Bolivariana - Clinica Universitaria Bolivariana ( Site 0602)
    Medellin, Antioquia 050036, Colombia
  • Neumo Investigaciones SAS ( Site 0622)
    Bogota, Cundinamarca 110311, Colombia
  • Centro Especializado en Enfermedades Pulmonares. ( Site 0620)
    Bogota, Cundinamarca 111831, Colombia
  • Fundacion Valle del Lili ( Site 0618)
    Cali, Valle Del Cauca 760032, Colombia
  • Centro Medico Imbanaco de Cali S.A ( Site 0619)
    Cali, Valle Del Cauca 760042, Colombia
  • MedPlus Medicina Prepagada S.A. ( Site 0612)
    Bogota, 110221, Colombia
  • Instituto Neumologico del Oriente S.A. ( Site 0649)
    Bucaramanga, 681004, Colombia
  • Inst. Prestadora de Servicios de Salud Universidad Antioquia ( Site 0621)
    Medellin, 050010, Colombia
  • MUDr. I. Cierna Peterova s.r.o. ( Site 0707)
    Brandys nad Labem, 250 01, Czechia
  • MediTrial s.r.o ( Site 0702)
    Jindrichuv Hradec III, 377 01, Czechia
  • Ordinace Pneumologie a diagnostiky Plicnich funkci ( Site 0705)
    Karlovy Vary, 360 17, Czechia
  • PNEUMO-NB s.r.o. ( Site 0710)
    Novy Bor, 473 01, Czechia
  • Nemocnice Tabor a.s. ( Site 0703)
    Tabor, 390 03, Czechia
  • Herlev Hospital ( Site 0803)
    Herlev, 2730, Denmark
  • Bispebjerg Hospital ( Site 0804)
    Kobenhavn NV, 2400, Denmark
  • Aerztezentrum Axel Springer Passage ( Site 1009)
    Berlin, 10969, Germany
  • Atemwegszentrum Neukoeln ( Site 1003)
    Berlin, 12043, Germany
  • Gemeinschaftspraxis Zentrum ( Site 1005)
    Frankfurt, 60318, Germany
  • Pneumologicum im Suedstadtforum ( Site 1004)
    Hannover, 30173, Germany
  • Pneumologenzentrum ( Site 1006)
    Leipzig, 04207, Germany
  • Ballenberger Freytag Wenisch Institut fuer klinische Forschung GmbH ( Site 1011)
    Neu-Isenburg, 63263, Germany
  • PneumoConsult Ulm ( Site 1008)
    Ulm, 89073, Germany
  • Clinipharm ( Site 2902)
    Guatemala, 01001, Guatemala
  • Celan SA ( Site 2900)
    Guatemala, 01010, Guatemala
  • Consultorio Privado Dr. Jeremias Guerra ( Site 2909)
    Guatemala, 01010, Guatemala
  • Clinica Medica Especializada en Neumologia ( Site 2901)
    Guatemala, 01011, Guatemala
  • Clinica Privada Dr. Jose Francisco Flores Lopez ( Site 2903)
    Guatemala, 01015, Guatemala
  • Dr Kenessey Albert Korhaz-Rendelointezet ( Site 1200)
    Balassagyarmat, 2660, Hungary
  • Synexus Magyarorszag Kft. ( Site 1208)
    Budapest, 1036, Hungary
  • Erzsebet Gondozohaz ( Site 1207)
    Godollo, 2100, Hungary
  • Synexus Magyarorszag Kft. ( Site 1210)
    Gyula, 5700, Hungary
  • Lumniczer Sandor Korhaz es Rendelointezet ( Site 1212)
    Kapuvar, 9330, Hungary
  • CRU Hungary KFT ( Site 1205)
    Miskolc, 3529, Hungary
  • Da Vinci Private Clinic - Da Vinci Maganklinika ( Site 1201)
    Pecs, 7626, Hungary
  • Puspokladanyi Egeszsegugyi Szolgaltato Nonprofit Kft ( Site 1203)
    Puspokladany, 4150, Hungary
  • Kaplan Medical Center ( Site 1300)
    Rehovot, 7661041, Israel
  • Azienda Ospedaliero Universitaria Careggi ( Site 1400)
    Firenze, 50134, Italy
  • Hospital Sultanah Bahiyah ( Site 1607)
    Alor Star, Kedah 05460, Malaysia
  • Hospital Taiping ( Site 1600)
    Taiping, Perak 34000, Malaysia
  • Hospital Pulau Pinang. ( Site 1606)
    George town, Pulau Pinang 10990, Malaysia
  • Universiti Teknologi MARA ( Site 1602)
    Batu Caves, Selangor 68100, Malaysia
  • Institut Perubatan Respiratori ( Site 1605)
    Kuala Lumpur, 53000, Malaysia
  • University Malaya Medical Centre ( Site 1601)
    Kuala Lumpur, 59100, Malaysia
  • Southern Clinical Trials - Waitemata ( Site 0230)
    Auckland, 0626, New Zealand

Showing the first 100 of 171 sites across 20 countries.

08

References and documents

Publications

  • Dicpinigaitis PV, Birring SS, Blaiss M, McGarvey LP, Morice AH, Pavord ID, Satia I, Smith JA, La Rosa C, Li Q, Nguyen AM, Schelfhout J, Tzontcheva A, Muccino D. Demographic, clinical, and patient-reported outcome data from 2 global, phase 3 trials of chronic cough. Ann Allergy Asthma Immunol. 2023 Jan;130(1):60-66. doi: 10.1016/j.anai.2022.05.003. Epub 2022 May 13. PubMed 35569802 ↗
  • McGarvey LP, Birring SS, Morice AH, Dicpinigaitis PV, Pavord ID, Schelfhout J, Nguyen AM, Li Q, Tzontcheva A, Iskold B, Green SA, Rosa C, Muccino DR, Smith JA; COUGH-1 and COUGH-2 Investigators. Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet. 2022 Mar 5;399(10328):909-923. doi: 10.1016/S0140-6736(21)02348-5. PubMed 35248186 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 26, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

09

Registry details

Key details

Study ID
NCT03449147
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Feb 28, 2018
Start date
Mar 15, 2018
Primary completion
Aug 20, 2020
Completion
Oct 30, 2020
Results posted
Sep 2, 2021
Last update
Sep 2, 2021

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2021. You cannot join it, but the record below documents what was studied.

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