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CompletedNCT03449134Updated Jun 16, 2021Results posted

A Study of Gefapixant (MK-7264) in Adult Participants With Chronic Cough (MK-7264-027)

A Phase 3 interventional study of Placebo and Gefapixant in Chronic Cough, sponsored by Merck Sharp & Dohme LLC. Completed at 156 sites in 17 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-06-16.

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

Phase
Phase 3
Study type
Interventional
Enrollment
732
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The main objectives of this study will be to evaluate the efficacy of gefapixant in reducing cough frequency as measured over a 24-hour period at Week 12, and to evaluate the safety and tolerability of gefapixant. The primary hypothesis is that at least one gefapixant dose is superior to placebo in reducing coughs per hour (over 24 hours) at Week 12.

Read the detailed description

The study will include a screening period to determine participant inclusion, and the Baseline visit will include 24 hours of objective measurement of cough. The study will consist of two treatment periods, a main 12-week treatment period and a 40-week extension period (52 weeks total treatment), followed by a 14-day telephone follow-up period.

Participants at selected sites and countries who complete the main and extension study periods may consent to participate in an observational, 3-month, Off-treatment Durability Study Period, which extends the Estimated Study Completion Date. The Off-treatment Durability Study Period will explore the impact of withdrawing gefapixant in refractory or unexplained chronic cough participants who have been treated for 1 year.

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
  • Female participants are eligible if not pregnant, not breastfeeding, and either not of childbearing potential, or agree 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
  • Has forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) ratio \<60%
  • 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) \<30mL/min/1.73 m\^2 at Screening OR 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 systolic blood pressure >160 mm Hg or diastolic blood pressure >90 mm Hg at Screening
  • 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 or is currently participating in or has participated in an interventional clinical study
  • Had significantly abnormal laboratory tests at Screening
04

Study design

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

Study arms

  • Placebo comparator
    Placebo

    Participants receive dose-matched placebo tablets twice daily (BID) during the 12-week main study period and 40-week extension period.

    Drug: Placebo

  • Experimental
    Gefapixant 15 mg BID

    Participants receive a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 12-week main study period and 40-week extension period.

    Drug: Placebo · Drug: Gefapixant

  • Experimental
    Gefapixant 45 mg BID

    Participants receive a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 12-week main study period and 40-week extension period.

    Drug: Placebo · Drug: Gefapixant

Interventions

  • DrugPlacebo

    Participants receive dose-matched placebo tablets orally BID during the 12-week main study period and during the 40-week extension period.

  • DrugGefapixant

    Gefapixant 15 mg or 45 mg tablet administered orally BID during the 12-week main study period and during the 40-week extension period, according to randomization.

    Also known as: MK-7264

05

What researchers measure

Primary outcomes

  1. Model-Based Geometric Mean Ratio (GMR) of 24-hour Objective Coughs Per Hour (Week 12/Baseline)

    24-hour objective coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) divided by 24 hours (denominator could be different if the recording period was actually \<24 hours but ≥20 hours). Assessment was based on 24-hour sound recordings using a digital recording device which recorded sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough counts to determine geometric mean (GM) 24-hour objective coughs per hour at baseline and Week 12 on the original scale. The GMR corresponding to the Week 12 GM 24-hour objective coughs per hour divided by the Baseline GM 24-hour objective coughs per hour was reported for all treatment study arms.

    Time frame: Baseline, Week 12

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

    An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with at least one AE during either the 52-week treatment period or 2-week telephone follow-up was reported for all treatment study arms.

    Time frame: Up to approximately 54 weeks

  3. Number of Participants Who Discontinued Treatment Due to AEs

    An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study intervention during the 52-week treatment period due to an AE for which the action taken was listed as 'drug withdrawn' was reported for all treatment study arms.

    Time frame: Up to approximately 52 weeks

Secondary outcomes

  1. Model-Based Geometric Mean Ratio (GMR) of Awake Objective Coughs Per Hour (Week 12/Baseline)

    Awake objective coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) while the participant is awake divided by the total duration (in hours) for the monitoring period that the participant was awake. Assessment was based on 24-hour sound recordings using a digital recording device which recorded sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. A longitudinal ANCOVA model was applied to log-transformed cough counts to determine GM awake objective coughs per hour at baseline and Week 12 on the original scale. The GMR corresponding to the Week 12 GM awake objective coughs per hour divided by the Baseline GM awake objective coughs per hour was reported for all treatment study arms.

    Time frame: Baseline, Week 12

  2. Percentage of Participants (Model-Based) With a ≤ -30% Change From Baseline in 24-hour Objective Coughs Per Hour at Week 12

    24-hour coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) divided by 24 hours (denominator could be different if the recording period was actually \<24 hours but ≥20 hours). Assessment based on 24-hour sound recordings using a digital recording device. Percent change in 24-hour coughs per hour = (change from baseline in 24-hour coughs per hour / baseline 24-hour coughs per hour) ×100%. Negative values indicate a decrease in cough rate, while positive values indicate an increase in cough rate. A participant was considered a responder if the percent change from baseline in 24-hour coughs per hour was ≤ -30% (or a ≥30% reduction from baseline); a participant was considered a non-responder otherwise. The percentage of participants (logistic regression model-based) with a ≤ -30% change from baseline in 24-hour coughs per hour at Week 12 (≥30% reduction from baseline) was reported for all treatment study arms.

    Time frame: Baseline, Week 12

  3. Percentage of Participants (Model-Based) With a ≤ -1.3-point Change From Baseline in Mean Weekly Cough Severity Diary (CSD) Total Score at Week 12

    The CSD evaluates frequency of cough, intensity of cough and disruption and has a total of 7 items, each with scores 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 total score was defined as the average of the mean total daily scores collected during the week prior to each visit. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Day -6 to Day 0). Participants were considered responders if the change from baseline in mean weekly CSD total score was ≤ -1.3 points (or a ≥1.3 point reduction from baseline); and considered a non-responder otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with a ≤ -1.3 point change from baseline in CSD at Week 12 (or ≥1.3 point reduction from baseline) was reported for all treatment study arms.

    Time frame: Baseline, Week 12

  4. Percentage of Participants (Model-Based) With a ≤ -2.7-point Change From Baseline in Mean Weekly CSD Total Score at Week 12

    The CSD evaluates frequency of cough, intensity of cough and disruption and has a total of 7 items, each with scores 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 total score was defined as the average of the mean total daily scores collected during the week prior to each visit. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Day -6 to Day 0). Participants were considered responders if the change from baseline in mean weekly CSD total score was ≤ -2.7 points (or a ≥2.7 point reduction from baseline); and considered a non-responder otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with a ≤ -2.7 point change from baseline in CSD at Week 12 (or ≥2.7 point reduction from baseline) was reported for all treatment study arms.

    Time frame: Baseline, Week 12

  5. Percentage of Participants (Model-Based) With a ≤ -30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 12

    Cough severity was scored using the Cough Severity VAS, a single-item question asking the participant to rate the severity of their cough "today" using a 100 mm VAS (100-point scale) ranging from 0 ("No Cough") to 100 ("Extremely Severe Cough"). Mean weekly VAS score was derived as the average of VAS scores collected during the week prior to each visit. Baseline was defined as the average VAS scores collected during the week prior to Day 1 (Day -6 to Day 0). A participant was considered a responder if the change from baseline in mean weekly Cough Severity VAS score was ≤-30 mm (or a ≥30 mm reduction from baseline); participants considered non-responders otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with ≤ -30 mm change from baseline in Cough Severity VAS at Week 12 (≥30 mm reduction from baseline) was reported for all treatment study arms.

    Time frame: Baseline, Week 12

  6. Percentage of Participants (Model-Based) With a ≥1.3-point Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 12

    The LCQ assesses the impact of chronic cough on health-related quality of life. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of individual item score within the domain divided by the number of items in the domain. LCQ total score is the sum of the three domain scores and ranges from 3-21; with a higher score corresponding to a better health status. A participant was considered a responder if the change from baseline in LCQ total score was ≥1.3-points (increase from baseline); a participant was considered a non-responder otherwise. The percentage of participants (logistic regression model-based) with a ≥1.3-point change from baseline in LCQ total score at Week 12 was reported for all treatment study arms.

    Time frame: Baseline, Week 12

06

Results

Posted Jun 16, 2021

Participant flow

52-Week Treatment Period
Participant flow — 52-Week Treatment Period
MilestonePlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Started244244244
Treated243244243
Completed199200184
Not completed454460
Withdrew: Death210
Withdrew: Lost to follow-up211
Withdrew: Physician decision233
Withdrew: Screen failure101
Withdrew: Withdrawal by subject373955
Withdrew: Site closure100
12-Week Off-Treatment Durability Period
Participant flow — 12-Week Off-Treatment Durability Period
MilestonePlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Started101813
Completed101813
Not completed000

Outcome measures

PrimaryModel-Based Geometric Mean Ratio (GMR) of 24-hour Objective Coughs Per Hour (Week 12/Baseline)

24-hour objective coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) divided by 24 hours (denominator could be different if the recording period was actually \<24 hours but ≥20 hours). Assessment was based on 24-hour sound recordings using a digital recording device which recorded sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough counts to determine geometric mean (GM) 24-hour objective coughs per hour at baseline and Week 12 on the original scale. The GMR corresponding to the Week 12 GM 24-hour objective coughs per hour divided by the Baseline GM 24-hour objective coughs per hour was reported for all treatment study arms.

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · ratio
Model-Based Geometric Mean Ratio (GMR) of 24-hour Objective Coughs Per Hour (Week 12/Baseline)
ratioPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Model-Based Geometric Mean Ratio (GMR) of 24-hour Objective Coughs Per Hour (Week 12/Baseline)0.47 (0.41 to 0.54)0.48 (0.41 to 0.55)0.38 (0.33 to 0.44)
Statistical analysis
  • Placebo vs Gefapixant 45 mg BID · ANCOVA · p = 0.041 (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 percent change difference: -18.45 · 95% CI -32.92 to -0.86
  • Placebo vs Gefapixant 15 mg BID · ANCOVA · p = 0.874 (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 percent change difference: 1.56 · 95% CI -16.13 to 22.99
PrimaryNumber of Participants Experiencing At Least One Adverse Event (AE) During Treatment and Follow-up

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with at least one AE during either the 52-week treatment period or 2-week telephone follow-up was reported for all treatment study arms.

Time frame:
Up to approximately 54 weeks
Reported as:
Count of participants · Participants
Number of Participants Experiencing At Least One Adverse Event (AE) During Treatment and Follow-up
ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Number of Participants Experiencing At Least One Adverse Event (AE) During Treatment and Follow-up184186208
PrimaryNumber of Participants Who Discontinued Treatment Due to AEs

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinued study intervention during the 52-week treatment period due to an AE for which the action taken was listed as 'drug withdrawn' was reported for all treatment study arms.

Time frame:
Up to approximately 52 weeks
Reported as:
Count of participants · Participants
Number of Participants Who Discontinued Treatment Due to AEs
ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Number of Participants Who Discontinued Treatment Due to AEs141551
SecondaryModel-Based Geometric Mean Ratio (GMR) of Awake Objective Coughs Per Hour (Week 12/Baseline)

Awake objective coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) while the participant is awake divided by the total duration (in hours) for the monitoring period that the participant was awake. Assessment was based on 24-hour sound recordings using a digital recording device which recorded sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. A longitudinal ANCOVA model was applied to log-transformed cough counts to determine GM awake objective coughs per hour at baseline and Week 12 on the original scale. The GMR corresponding to the Week 12 GM awake objective coughs per hour divided by the Baseline GM awake objective coughs per hour was reported for all treatment study arms.

Time frame:
Baseline, Week 12
Reported as:
Geometric mean · ratio
Model-Based Geometric Mean Ratio (GMR) of Awake Objective Coughs Per Hour (Week 12/Baseline)
ratioPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Model-Based Geometric Mean Ratio (GMR) of Awake Objective Coughs Per Hour (Week 12/Baseline)0.46 (0.40 to 0.53)0.47 (0.41 to 0.55)0.38 (0.33 to 0.44)
Statistical analysis
  • Placebo vs Gefapixant 45 mg BID · ANCOVA · p = 0.056 (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 percent change difference: -17.68 · 95% CI -32.57 to 0.50
  • Placebo vs Gefapixant 15 mg BID · ANCOVA · p = 0.770 (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 percent change difference: 2.95 · 95% CI -15.33 to 25.19
SecondaryPercentage of Participants (Model-Based) With a ≤ -30% Change From Baseline in 24-hour Objective Coughs Per Hour at Week 12

24-hour coughs per hour was defined as the total number of cough events during the monitoring period (24-hour interval) divided by 24 hours (denominator could be different if the recording period was actually \<24 hours but ≥20 hours). Assessment based on 24-hour sound recordings using a digital recording device. Percent change in 24-hour coughs per hour = (change from baseline in 24-hour coughs per hour / baseline 24-hour coughs per hour) ×100%. Negative values indicate a decrease in cough rate, while positive values indicate an increase in cough rate. A participant was considered a responder if the percent change from baseline in 24-hour coughs per hour was ≤ -30% (or a ≥30% reduction from baseline); a participant was considered a non-responder otherwise. The percentage of participants (logistic regression model-based) with a ≤ -30% change from baseline in 24-hour coughs per hour at Week 12 (≥30% reduction from baseline) was reported for all treatment study arms.

Time frame:
Baseline, Week 12
Reported as:
Number · Percentage of Participants
Percentage of Participants (Model-Based) With a ≤ -30% Change From Baseline in 24-hour Objective Coughs Per Hour at Week 12
Percentage of ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Percentage of Participants (Model-Based) With a ≤ -30% Change From Baseline in 24-hour Objective Coughs Per Hour at Week 1265.966.269.9
Statistical analysis
  • Placebo vs Gefapixant 45 mg BID · Regression, Logistic · p = 0.416 · Odds ratio (or): 1.20 · 95% CI 0.77 to 1.86
  • Placebo vs Gefapixant 15 mg BID · Regression, Logistic · p = 0.948 · Odds ratio (or): 1.01 · 95% CI 0.66 to 1.55
SecondaryPercentage of Participants (Model-Based) With a ≤ -1.3-point Change From Baseline in Mean Weekly Cough Severity Diary (CSD) Total Score at Week 12

The CSD evaluates frequency of cough, intensity of cough and disruption and has a total of 7 items, each with scores 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 total score was defined as the average of the mean total daily scores collected during the week prior to each visit. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Day -6 to Day 0). Participants were considered responders if the change from baseline in mean weekly CSD total score was ≤ -1.3 points (or a ≥1.3 point reduction from baseline); and considered a non-responder otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with a ≤ -1.3 point change from baseline in CSD at Week 12 (or ≥1.3 point reduction from baseline) was reported for all treatment study arms.

Time frame:
Baseline, Week 12
Reported as:
Number · Percentage of Participants
Percentage of Participants (Model-Based) With a ≤ -1.3-point Change From Baseline in Mean Weekly Cough Severity Diary (CSD) Total Score at Week 12
Percentage of ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Percentage of Participants (Model-Based) With a ≤ -1.3-point Change From Baseline in Mean Weekly Cough Severity Diary (CSD) Total Score at Week 1252.462.160.5
Statistical analysis
  • Placebo vs Gefapixant 45 mg BID · Odds ratio (or): 1.39 · 95% CI 0.94 to 2.05
  • Placebo vs Gefapixant 15 mg BID · Odds ratio (or): 1.48 · 95% CI 1.01 to 2.18
SecondaryPercentage of Participants (Model-Based) With a ≤ -2.7-point Change From Baseline in Mean Weekly CSD Total Score at Week 12

The CSD evaluates frequency of cough, intensity of cough and disruption and has a total of 7 items, each with scores 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 total score was defined as the average of the mean total daily scores collected during the week prior to each visit. Baseline was defined as the average CSD scores collected during the week prior to Day 1 (Day -6 to Day 0). Participants were considered responders if the change from baseline in mean weekly CSD total score was ≤ -2.7 points (or a ≥2.7 point reduction from baseline); and considered a non-responder otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with a ≤ -2.7 point change from baseline in CSD at Week 12 (or ≥2.7 point reduction from baseline) was reported for all treatment study arms.

Time frame:
Baseline, Week 12
Reported as:
Number · Percentage of Participants
Percentage of Participants (Model-Based) With a ≤ -2.7-point Change From Baseline in Mean Weekly CSD Total Score at Week 12
Percentage of ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Percentage of Participants (Model-Based) With a ≤ -2.7-point Change From Baseline in Mean Weekly CSD Total Score at Week 1228.637.940.1
Statistical analysis
  • Placebo vs Gefapixant 45 mg BID · Odds ratio (or): 1.68 · 95% CI 1.11 to 2.54
  • Placebo vs Gefapixant 15 mg BID · Odds ratio (or): 1.53 · 95% CI 1.01 to 2.30
SecondaryPercentage of Participants (Model-Based) With a ≤ -30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 12

Cough severity was scored using the Cough Severity VAS, a single-item question asking the participant to rate the severity of their cough "today" using a 100 mm VAS (100-point scale) ranging from 0 ("No Cough") to 100 ("Extremely Severe Cough"). Mean weekly VAS score was derived as the average of VAS scores collected during the week prior to each visit. Baseline was defined as the average VAS scores collected during the week prior to Day 1 (Day -6 to Day 0). A participant was considered a responder if the change from baseline in mean weekly Cough Severity VAS score was ≤-30 mm (or a ≥30 mm reduction from baseline); participants considered non-responders otherwise. Negative values indicate a decrease in cough severity, while positive values indicate an increase in cough severity. The percentage of participants (logistic regression model-based) with ≤ -30 mm change from baseline in Cough Severity VAS at Week 12 (≥30 mm reduction from baseline) was reported for all treatment study arms.

Time frame:
Baseline, Week 12
Reported as:
Number · Percentage of Participants
Percentage of Participants (Model-Based) With a ≤ -30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 12
Percentage of ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Percentage of Participants (Model-Based) With a ≤ -30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 1231.336.741.2
Statistical analysis
  • Placebo vs Gefapixant 45 mg BID · Odds ratio (or): 1.54 · 95% CI 1.03 to 2.30
  • Placebo vs Gefapixant 15 mg BID · Odds ratio (or): 1.27 · 95% CI 0.86 to 1.89
SecondaryPercentage of Participants (Model-Based) With a ≥1.3-point Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 12

The LCQ assesses the impact of chronic cough on health-related quality of life. It consists of 19 items which are divided over 3 domains: Physical (items 1, 2, 3, 9, 10, 11, 14 and 15), Psychological (4, 5, 6, 12, 13, 16, and 17), and Social (7, 8, 18, 19). A 7-point Likert scale is used to rate each item. For each domain, the domain score (range 1-7) is the sum of individual item score within the domain divided by the number of items in the domain. LCQ total score is the sum of the three domain scores and ranges from 3-21; with a higher score corresponding to a better health status. A participant was considered a responder if the change from baseline in LCQ total score was ≥1.3-points (increase from baseline); a participant was considered a non-responder otherwise. The percentage of participants (logistic regression model-based) with a ≥1.3-point change from baseline in LCQ total score at Week 12 was reported for all treatment study arms.

Time frame:
Baseline, Week 12
Reported as:
Number · Percentage of Participants
Percentage of Participants (Model-Based) With a ≥1.3-point Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 12
Percentage of ParticipantsPlaceboGefapixant 15 mg BIDGefapixant 45 mg BID
Percentage of Participants (Model-Based) With a ≥1.3-point Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 1261.368.867.3
Statistical analysis
  • Placebo vs Gefapixant 45 mg BID · Odds ratio (or): 1.30 · 95% CI 0.85 to 1.98
  • Placebo vs Gefapixant 15 mg BID · Odds ratio (or): 1.39 · 95% CI 0.92 to 2.12

Adverse events

Collected over On-Treatment Period (plus 2-week telephone follow-up): 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
Placebo2/244 (0.8%)14/243 (5.8%)129/243 (53.1%)
Gefapixant 15 mg BID1/244 (0.4%)17/244 (7%)140/244 (57.4%)
Gefapixant 45 mg BID0/244 (0%)13/243 (5.3%)179/243 (73.7%)
Placebo: Off-Tx0/10 (0%)0/10 (0%)0/10 (0%)
Gefapixant 15 mg BID: Off-Tx0/18 (0%)0/18 (0%)1/18 (5.6%)
Gefapixant 45 mg BID: Off-Tx0/13 (0%)0/13 (0%)1/13 (7.7%)
Most frequent serious events
Showing 10 of 50
Most frequent serious events
EventPlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDPlacebo: Off-TxGefapixant 15 mg BID: Off-TxGefapixant 45 mg BID: Off-Tx
Abdominal adhesionsGastrointestinal disorders0/2430/2441/2430/100/180/13
Abdominal wall cystGastrointestinal disorders1/2430/2440/2430/100/180/13
Duodenal ulcer haemorrhageGastrointestinal disorders0/2430/2441/2430/100/180/13
NauseaGastrointestinal disorders1/2430/2440/2430/100/180/13
VomitingGastrointestinal disorders1/2430/2440/2430/100/180/13
Accidental deathGeneral disorders1/2430/2440/2430/100/180/13
DeathGeneral disorders1/2430/2440/2430/100/180/13
Papilloma viral infectionInfections and infestations1/2430/2440/2430/100/180/13
TonsillitisInfections and infestations0/2430/2441/2430/100/180/13
Urinary tract infectionInfections and infestations1/2430/2440/2430/100/180/13
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 disorders8/24322/24488/2430/100/180/13
NasopharyngitisInfections and infestations51/24347/24450/2430/101/180/13
HeadacheNervous system disorders31/24334/24429/2430/100/180/13
AgeusiaNervous system disorders0/2433/24433/2430/100/180/13
Taste disorderNervous system disorders2/2432/24424/2430/100/180/13
Back painMusculoskeletal and connective tissue disorders19/24314/24420/2430/100/180/13
BronchitisInfections and infestations11/24320/24411/2430/100/180/13
Respiratory tract infectionInfections and infestations1/2432/2440/2430/100/181/13
Upper respiratory tract infectionInfections and infestations9/24318/24413/2430/100/180/13
NauseaGastrointestinal disorders13/2438/24417/2430/100/180/13

Baseline characteristics

Age, Continuous
Age, Continuous(Years)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
Mean57.9 ± 13.159.6 ± 11.759.5 ± 13.159.0 ± 12.6
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
Female182181181544
Male626363188
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
Hispanic or Latino333533101
Not Hispanic or Latino204205208617
Unknown or Not Reported74314
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
American Indian or Alaska Native76821
Asian353534104
Native Hawaiian or Other Pacific Islander0000
Black or African American43411
White190195187572
More than one race851124
Unknown or Not Reported0000
Geographic Region
Geographic Region(Participants)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
Asia Pacific353434103
Europe121123122366
North America565556167
Others31323295
Missing1001
Baseline 24-hour Coughs per Hour
Baseline 24-hour Coughs per Hour(coughs/hour)PlaceboGefapixant 15 mg BIDGefapixant 45 mg BIDTotal
Mean38.07 ± 79.4226.79 ± 21.1328.53 ± 37.1431.10 ± 52.04
07

Study locations

156 sites
  • Research Solutions of Arizona PC ( Site 0036)
    Litchfield Park, Arizona 85340, United States
  • Medical Research of AZ ( Site 0060)
    Scottsdale, Arizona 85251, United States
  • Biosolutions Clinical Research Center ( Site 0070)
    La Mesa, California 91942, United States
  • Center for Clinical Trials, LLC ( Site 0059)
    Paramount, California 90723, United States
  • Sher Allergy Specialists/Center For Cough ( Site 0078)
    Largo, Florida 33778, United States
  • Well Pharma Medical Research, Corp. ( Site 0093)
    Miami, Florida 33143, United States
  • Florida Pulmonary Research Institute, LLC ( Site 0019)
    Winter Park, Florida 32789, United States
  • Midwest Allergy Sinus Asthma, SC ( Site 0081)
    Normal, Illinois 61761, United States
  • Cotton-O'Neil Clinical Research Center ( Site 0052)
    Topeka, Kansas 66606, United States
  • BreatheAmerica Inc ( Site 0048)
    Shreveport, Louisiana 71106, United States
  • Clinical Research Institute LLC ( Site 0004)
    Minneapolis, Minnesota 55402, United States
  • The Center for Pharmaceutical Research PC ( Site 0016)
    Kansas City, Missouri 64114, United States
  • American Health Research ( Site 0082)
    Charlotte, North Carolina 28207, United States
  • Clinical Research of Gastonia ( Site 0043)
    Gastonia, North Carolina 28054, United States
  • Bernstein Clinical Research Center, LLC ( Site 0005)
    Cincinnati, Ohio 45231, United States
  • Vital Prospects Clinical Research Institute, PC ( Site 0037)
    Tulsa, Oklahoma 74136, United States
  • Asthma Nasal Disease & Allergy Research Center of New England ( Site 0075)
    East Providence, Rhode Island 02914, United States
  • Sirius Clinical Research, LLC ( Site 0102)
    Austin, Texas 78759, United States
  • Pharmaceutical Research & Consulting, Inc. ( Site 0029)
    Dallas, Texas 75231, United States
  • Mainland Medical Research Institute ( Site 0003)
    Dickinson, Texas 77539, United States
  • Diagnostics Research Group ( Site 0035)
    San Antonio, Texas 78229, United States
  • Allergy & Asthma Center ( Site 0001)
    Waco, Texas 76712, United States
  • Intermountain Clinical Research ( Site 0033)
    Draper, Utah 84020, United States
  • Charlottesville Medical Research Center, LLC ( Site 0006)
    Charlottesville, Virginia 22911, United States
  • Pulmonary Associates of Richmond Inc. ( Site 0101)
    Richmond, Virginia 23225, United States
  • National Clinical Research-Richmond, Inc. ( Site 0073)
    Richmond, Virginia 23294, United States
  • Lung and Sleep Specialists ( Site 0091)
    Williamsburg, Virginia 23188, United States
  • InAER Investigaciones en Alergia y Enfermedades Respiratorias ( Site 0324)
    Caba, Buenos Aires C1425BEN, Argentina
  • Fundacion CIDEA ( Site 0323)
    Ciudad de Buenos Aires, Buenos Aires C1121ABE, Argentina
  • Instituto Ave Pulmo ( Site 0322)
    Mar del Plata, Buenos Aires B7602DCK, Argentina
  • Centro Medico Privado de Reumatologia ( Site 0309)
    San Miguel de Tucuman, Tucuman T4000AXL, Argentina
  • Investigaciones en Patologias Respiratorias ( Site 0325)
    San Miguel de Tucuman, Tucuman T4000IAR, Argentina
  • Centro Medico Dra De Salvo ( Site 0310)
    Buenos Aires, C1426ABP, Argentina
  • CEMEDIC - Centro de Especialidades Medicas ( Site 0304)
    Ciudad Autonoma de Buenos Aires, C1407GTN, Argentina
  • Hospital Privado Universitario de Cordoba ( Site 0313)
    Cordoba, X5016KEH, Argentina
  • Fundacion Scherbovsky ( Site 0300)
    Mendoza, M5500AXR, Argentina
  • Canadian Phase Onward Inc. ( Site 0509)
    Toronto, Ontario M3J 2C5, Canada
  • Recherche GCP Research ( Site 0500)
    Montreal, Quebec H1M 1B1, Canada
  • 167877 Canada Inc. Dr. Jaime Del Carpio ( Site 0506)
    Montreal, Quebec H3G 1L5, Canada
  • Dynamik Research ( Site 0505)
    Pointe-Claire, Quebec H9R 3J1, Canada
  • Q & T Research Sherbrooke Inc. ( Site 0512)
    Sherbrooke, Quebec J1J 2G2, Canada
  • CIC Mauricie Inc. ( Site 0503)
    Trois-Rivieres, Quebec G8T 7A1, Canada
  • Diex Recherche Quebec Inc ( Site 0515)
    Quebec, G1N 4V3, Canada
  • MUDr. I. Cierna Peterova s.r.o. ( Site 0707)
    Brandys nad Labem, 250 01, Czechia
  • Plicni ambulance ( Site 0701)
    Rokycany, 337 22, Czechia
  • Plicni stredisko Teplice s. r. o ( Site 0700)
    Teplice, 415 01, Czechia
  • Pneumologie Varnsdorf S.R.O. ( Site 0706)
    Varnsdorf, 407 47, Czechia
  • CCBR AS Aalborg, Center for Clinical & Basic Research ( Site 0802)
    Aalborg, 9000, Denmark
  • Herlev Hospital ( Site 0803)
    Herlev, 2730, Denmark
  • CCBR AS Vejle, Center for Clinical & Basic Research ( Site 0801)
    Vejle, 7100, Denmark
  • Hopital Cavale Blanche ( Site 0909)
    Brest, 29609, France
  • Hopital Nord du Marseille ( Site 0910)
    Marseille, 13015, France
  • Hopital Arnaud de Villeneuve ( Site 0905)
    Montpellier, 34295, France
  • CHU Hotel Dieu Nantes ( Site 0906)
    Nantes, 44093, France
  • CHU de Toulouse - Hopital Larrey ( Site 0900)
    Toulouse, 31100, France
  • Dr Kenessey Albert Korhaz-Rendelointezet ( Site 1200)
    Balassagyarmat, 2660, Hungary
  • Erzsebet Gondozohaz ( Site 1207)
    Godollo, 2100, Hungary
  • Petz Aladar Megyei Oktato Korhaz ( Site 1206)
    Gyor, 9024, Hungary
  • Synexus Magyarorszag Kft. ( Site 1210)
    Gyula, 5700, Hungary
  • CRU Hungary KFT ( Site 1205)
    Miskolc, 3529, Hungary
  • Hillel Yaffe Medical Center ( Site 1303)
    Hadera, 3810101, Israel
  • Carmel Medical Center ( Site 1305)
    Haifa, 3436212, Israel
  • Meir Medical Center ( Site 1301)
    Kfar Saba, 4428164, Israel
  • Rabin Medical Center ( Site 1302)
    Petah-Tikva, 4941492, Israel
  • Chaim Sheba Medical Center. ( Site 1304)
    Ramat Gan, 5265601, Israel
  • National Hospital Organization Nagoya Medical Center ( Site 1539)
    Nagoya, Aichi 460-0001, Japan
  • Nagoya City University Hospital ( Site 1528)
    Nagoya, Aichi 467-8602, Japan
  • National Hospital Organization Ehime Medical Center ( Site 1556)
    Toon, Ehime 791-0281, Japan
  • Idaimae Minamiyojo Int Clinic ( Site 1521)
    Sapporo, Hokkaido 064-0804, Japan
  • Terada Clinic Respiratory Medicine & General Practice ( Site 1565)
    Himeji, Hyogo 670-0849, Japan
  • Kinki Central Hospital ( Site 1576)
    Itami, Hyogo 664-8533, Japan
  • Itami City Hospital ( Site 1580)
    Itami, Hyogo 664-8540, Japan
  • National Hospital Organization Ibarakihigashi National Hospital ( Site 1526)
    Naka-gun, Ibaraki 319-1113, Japan
  • Ishikawa Prefectural Central Hospital ( Site 1554)
    Kanazawa, Ishikawa 920-8530, Japan
  • Kanazawa University Hospital ( Site 1536)
    Kanazawa, Ishikawa 920-8641, Japan
  • Komatsu Municipal Hospital ( Site 1508)
    Komatsu, Ishikawa 923-8560, Japan
  • Kamei Internal Medicine and Respiratory Clinic ( Site 1509)
    Takamatsu, Kagawa 761-8073, Japan
  • Fujisawa City Hospital ( Site 1505)
    Fujisawa, Kanagawa 251-8550, Japan
  • Yokohama City Minato Red Cross Hospital ( Site 1506)
    Yokohama, Kanagawa 231-8682, Japan
  • Medical Corporation Shintokai Yokohama Minoru Clinic ( Site 1568)
    Yokohama, Kanagawa 232-0064, Japan
  • Saiseikai Yokohamashi Nanbu Hospital ( Site 1533)
    Yokohama, Kanagawa 234-8503, Japan
  • Kanagawa Cardiovascular and Respiratory Center ( Site 1503)
    Yokohama, Kanagawa 236-0051, Japan
  • Matsusaka City Hospital ( Site 1525)
    Matsusaka, Mie 515-8544, Japan
  • Nagaoka Red Cross Hospital ( Site 1507)
    Nagaoka, Niigata 940-2085, Japan
  • National Hospital Organization Minami-Okayama Medical Center ( Site 1553)
    Tsukubo-gun, Okayama 701-0304, Japan
  • Urasoe General Hospital ( Site 1572)
    Urasoe, Okinawa 901-2132, Japan
  • Osaka Habikino Medical Center ( Site 1546)
    Habikino, Osaka 583-8588, Japan
  • Kawaguchi Respiratory Clinic ( Site 1504)
    Higashiosaka, Osaka 577-0843, Japan
  • National Hospital Organization Kinki-chuo Chest Medical Center ( Site 1519)
    Sakai, Osaka 591-8555, Japan
  • Tokyo Medical University Hachioji Medical Center ( Site 1569)
    Hachioji, Tokyo 193-0998, Japan
  • National Hospital Organization Tokyo National Hospital ( Site 1557)
    Kiyose, Tokyo 204-8585, Japan
  • National Hospital Organization Disaster Medical Center ( Site 1558)
    Tachikawa, Tokyo 190-0014, Japan
  • Shimonoseki City Hospital ( Site 1573)
    Shimonoseki, Yamaguchi 750-8520, Japan
  • National Hospital Organization Fukuoka Hospital ( Site 1552)
    Fukuoka, 811-1394, Japan
  • Hiroshima Allergy & Respiratory Clinic ( Site 1529)
    Hiroshima, 732-0052, Japan
  • Kyoto University Hospital ( Site 1547)
    Kyoto, 606-8507, Japan
  • JA Niigatakoseiren Niigata Medical Center ( Site 1522)
    Niigata, 950-2022, Japan
  • Shizuoka Prefectural Hospital Organization Shizuoka General Hospital ( Site 1524)
    Shizuoka, 420-8527, Japan
  • Juntendo University Hospital ( Site 1578)
    Tokyo, 113-8431, Japan
  • Tokyo Shinagawa Hospital ( Site 1560)
    Tokyo, 140-8522, Japan

Showing the first 100 of 156 sites across 17 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
NCT03449134
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Feb 28, 2018
Start date
Mar 14, 2018
Primary completion
Jun 5, 2020
Completion
Aug 17, 2020
Results posted
Jun 16, 2021
Last update
Jun 16, 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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