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NCT02476890

Effect of Gefapixant (MK-7264/AF-219) on Cough Reflex Sensitivity in Healthy and Chronic Cough Participants (MK-7264-014)

Completed Phase 2 Results posted Last updated 18 June 2019
What this trial tests

Phase 2 trial testing Gefapixant 100 mg in Refractory Chronic Cough in 36 participants. Completed in 20 October 2016.

Timeline
28 October 2015
Primary endpoint
20 October 2016
20 October 2016

Quick facts

Lead sponsorAfferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designcrossover
Maskingtriple
Primary purposetreatment
Enrollment36
Start date28 October 2015
Primary completion20 October 2016
Estimated completion20 October 2016

Drugs / interventions tested

Conditions studied

Sponsor

Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) — full company profile →

Who can join

Adults 18 to 80, any sex, with Refractory Chronic Cough. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Cough Reflex Sensitivity to Capsaicin in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined) Primary · Average of 1, 3, and 5 hours post-dose

The concentration of capsaicin inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of capsaicin for cough challenge were 0.3 micromoles (µM), 1 µM, 3 µM, 10 µM, 30 µM, 100 µM, 300 µM, and 1000 µM. The Measure Type is least-squares mean in natural log scale. The challenge agent was prepared by dilution of capsaicin with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to ev

C2 Response to Capsaicin (Periods 1 & 2)
GroupValue95% CI
Gefapixant 100 mg/Healthy3.052.6 – 3.5
Placebo/Healthy3.042.6 – 3.5
Gefapixant 100 mg/Chronic Cough1.721.3 – 2.1
Placebo/Chronic Cough1.411.0 – 1.8
C5 Response to Capsaicin (Periods 1 & 2)
GroupValue95% CI
Gefapixant 100 mg/Healthy4.463.9 – 5.0
Placebo/Healthy4.684.1 – 5.3
Gefapixant 100 mg/Chronic Cough2.311.9 – 2.8
Placebo/Chronic Cough2.051.6 – 2.5
Cough Reflex Sensitivity to Citric Acid in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined) Primary · Average of 1, 3, and 5 hours post-dose

The concentration of citric acid inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of citric acid for cough challenge were 1 millimoles (mM), 3 mM, 10 mM, 30 mM, 100 mM, 300 mM, 1 M, and 3 M. The Measure Type is least-squares mean in natural log scale. The challenge agent was prepared by dilution of citric acid with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evo

C2 Response to Citric Acid (Periods 1 & 2)
GroupValue95% CI
Gefapixant 100 mg/Healthy6.165.6 – 6.8
Placebo/Healthy5.615.0 – 6.2
Gefapixant 100 mg/Chronic Cough4.073.6 – 4.6
Placebo/Chronic Cough3.843.3 – 4.3
C5 Response to Citric Acid (Periods 1 & 2)
GroupValue95% CI
Gefapixant 100 mg/Healthy7.126.4 – 7.8
Placebo/Healthy6.826.1 – 7.6
Gefapixant 100 mg/Chronic Cough4.744.2 – 5.2
Placebo/Chronic Cough4.464.0 – 5.0
Cough Reflex Sensitivity to ATP in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined) Primary · Average of 1, 3, and 5 hours post-dose

The concentration of ATP inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of ATP for cough challenge were 0.1 mM, 0.3 mM, 1 mM, 3 mM, 10 mM, 30 mM, 100 mM, and 300 mM. The Measure Type is least-squares mean in natural log scale. The challenge agent was prepared by dilution of ATP with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentrations of inhaled solution required to evoke at least 2 (C2) or at least

C2 Response to ATP (Periods 1 & 2)
GroupValue95% CI
Gefapixant 100 mg/Healthy4.794.0 – 5.6
Placebo/Healthy3.903.1 – 4.7
Gefapixant 100 mg/Chronic Cough2.902.3 – 3.5
Placebo/Chronic Cough1.360.8 – 2.0
C5 Response to ATP (Periods 1 & 2)
GroupValue95% CI
Gefapixant 100 mg/Healthy5.615.3 – 5.9
Placebo/Healthy4.734.3 – 5.1
Gefapixant 100 mg/Chronic Cough3.522.9 – 4.2
Placebo/Chronic Cough2.221.6 – 2.9
Cough Reflex Sensitivity to Distilled Water in Participants Who Received Gefapixant 100 mg and Placebo (Period 1 & Period 2 Combined) Primary · Average of 1, 3, and 5 hours post-dose

The concentration of distilled water inducing at least 2 coughs (C2) and at least 5 coughs (C5) was assessed at 1, 3, and 5 hours post-dose in healthy and chronic cough participants. The concentrations of distilled water for cough challenge were 20%, 40%, 60%, 80%, and 100%. The Measure Type is least-squares mean in natural log scale. The number of coughs generated in 1 minute of exposure was recorded. The challenge agent was prepared by dilution of distilled water with saline, and was administered by inhalation. A mixed effects model used natural log-transformed values for the lowest concentr

C2 Response to Distilled Water (Periods 1 & 2)
GroupValue95% CI
Gefapixant 100 mg/Healthy4.724.6 – 4.8
Placebo/Healthy4.344.2 – 4.4
Gefapixant 100 mg/Chronic Cough4.424.3 – 4.5
Placebo/Chronic Cough4.124.0 – 4.2
C5 Response to Distilled Water (Periods 1 & 2)
GroupValue95% CI
Gefapixant 100 mg/Healthy4.854.6 – 5.1
Placebo/Healthy4.614.4 – 4.8
Gefapixant 100 mg/Chronic Cough4.514.4 – 4.6
Placebo/Chronic Cough4.244.1 – 4.4
Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only) Secondary · Baseline and one hour after the final cough challenge on treatment days

Chronic cough participants completed a visual analogue scale (VAS) to record cough severity, prior to dosing on the treatment day in each treatment period, and one hour after the final cough challenge on the treatment days. This was a 100mm VAS of cough severity from 'No Cough' (0) up to 'Worst Cough' (100). Participants were instructed to draw a line on the scale to indicate how severe they felt their cough was during the previous 1 hour on the treatment days. A negative change from Baseline was considered to indicate improvement in cough severity.

GroupValue95% CI
Gefapixant 100 mg/Chronic Cough-26.2-36.2 – -16.2
Placebo/Chronic Cough-8.2-18.7 – 2.2
Change From Baseline in Urge to Cough VAS After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only) Secondary · Baseline and one hour after final cough challenge on treatment days

Chronic cough participants completed a VAS to record the severity of their urge to cough, prior to dosing on the treatment day in each treatment period, and one hour after the final cough challenge on the treatment days. Participants marked the 100mm VAS at the extremes as 'No urge-to-cough' (0) and 'Worst urge-to-cough' (100). Participants were instructed to draw a single vertical line on the scale to indicate how severe their urge to cough was during the previous 1 hour on the treatment days. A negative change from Baseline was considered to indicate improvement in urge to cough.

GroupValue95% CI
Gefapixant 100 mg/Chronic Cough-29.8-38.9 – -20.7
Placebo/Chronic Cough-11.7-20.9 – -2.6
Change From Baseline in Cough Frequency After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only) Secondary · Baseline and for 24 hours after cough challenge on treatment days

An ambulatory cough recording device recorded all sounds chronic cough participants made during cough monitoring to measure the change from baseline in objective cough frequency on the treatment days. A negative change from Baseline was considered to indicate improvement in cough frequency

GroupValue95% CI
Gefapixant 100 mg/Chronic Cough-7.7-10.1 – -5.3
Placebo/Chronic Cough-4.1-6.5 – -1.7
Percentage of Participants Who Experienced One or More Adverse Events During Study Treatment and Follow up Secondary · Up to Day 18

A secondary endpoint of the trial was the percentage of participants receiving gefapixant 100 mg and placebo who had at least 1 adverse event (AE) over 4 days of treatment (including washout periods) in addition to 14 days (+3 days) until a post-treatment follow-up visit. An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with this treatment. Any worsening of a preexisting condition that is temporally associated with the use of the study drug is also an AE. The percentage of participants

GroupValue95% CI
Gefapixant 100 mg/Healthy100.0
Placebo/Healthy50.0
Gefapixant 100 mg/Chronic Cough95.8
Placebo/Chronic Cough33.3
Percentage of Participants Who Discontinued From the Study Due to an Adverse Event Secondary · Up to Day 4

A secondary endpoint of the trial was the percentage of participants receiving gefapixant 100 mg and placebo who discontinued from the study due to an AE. The percentage of participants who discontinued from the study due to an AE was assessed for days 1-4.

GroupValue95% CI
Gefapixant 100 mg/Healthy0
Placebo/Healthy0
Gefapixant 100 mg/Chronic Cough0
Placebo/Chronic Cough0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Day 18. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Gefapixant 100 mg/Healthy
Serious: 0/12 (0%)
Deaths: 0/12
Placebo/Healthy
Serious: 0/12 (0%)
Deaths: 0/12
Gefapixant 100 mg/Chronic Cough
Serious: 0/24 (0%)
Deaths: 0/24
Placebo/Chronic Cough
Serious: 0/24 (0%)
Deaths: 0/24
Other adverse events (21 terms — click to expand)

ReactionSystemGefapixant 100 mg/HealthyPlacebo/HealthyGefapixant 100 mg/Chronic …Placebo/Chronic Cough
DysgeusiaNervous system disorders
AgeusiaNervous system disorders
Dry mouthGastrointestinal disorders
HeadacheNervous system disorders
Hypoaesthesia oralGastrointestinal disorders
Paraesthesia oralGastrointestinal disorders
NauseaGastrointestinal disorders
Oral disorderGastrointestinal disorders
DizzinessNervous system disorders
SomnolenceNervous system disorders
Pharyngeal hypoaesthesiaRespiratory, thoracic and mediastinal disorders
DyspepsiaGastrointestinal disorders
VomitingGastrointestinal disorders
Neutrophil count decreasedInvestigations
HypogeusiaNervous system disorders
MigraineNervous system disorders
HaematuriaRenal and urinary disorders
Dry throatRespiratory, thoracic and mediastinal disorders
Increased upper airway secretionRespiratory, thoracic and mediastinal disorders
Pharyngeal disorderRespiratory, thoracic and mediastinal disorders
Pharyngeal oedemaRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT02476890 adverse events section.

Sponsor's own description

The primary objective of this study was to assess the effect of a single dose of gefapixant 100 mg on cough reflex sensitivity to various challenge agents (capsaicin, citric acid, adenosine triphosphate \[ATP\], and distilled water) in healthy and chronic cough participants.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Mechanisms and Rationale for Targeted Therapies in Refractory and Unexplained Chronic Cough.
    Mazzone SB, McGarvey L. · · 2021 · cited 73× · PMID 32748976 · DOI 10.1002/cpt.2003
  2. Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough: A Systematic Review and Dose-Response Meta-Analysis.
    Kum E, Patel M, Diab N, Wahab M, et al · · 2023 · cited 27× · PMID 37694849 · DOI 10.1001/jama.2023.18035
  3. Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics.
    Knezevic NN, Yekkirala A, Yaksh TL. · · 2017 · cited 24× · PMID 29049116 · DOI 10.1213/ane.0000000000002442
  4. Safety and efficacy of gefapixant, a novel drug for the treatment of chronic cough: A systematic review and meta-analysis of randomized controlled trials.
    Abu-Zaid A, Aljaili AK, Althaqib A, Adem F, et al · · 2021 · cited 12× · PMID 34012479 · DOI 10.4103/atm.atm_417_20
  5. Systematic literature review of treatments used for refractory or unexplained chronic cough in adults.
    Bali V, Kardos P, Page C, Rogliani P, et al · · 2024 · cited 5× · PMID 38444993 · DOI 10.4103/atm.atm_105_23

Verify or expand the search:

Other recruiting trials for Refractory Chronic Cough

Currently open trials in the same condition.

Other Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) trials

Trials by the same sponsor.

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Data sources for this page

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