A 12-Week Study in Participants With Refractory Chronic Cough (MK-7264-012)

NCT02612610 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 7264-012AF219-0122015-005064-42
• Study Type: interventional
• Target: 253
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is designed to evaluate the efficacy of three dose regimens of gefapixant (\[MK-7264\] 7.5 mg, 20 mg, and 50 mg) relative to placebo in reducing awake objective cough frequency. The primary hypothesis for this trial is that at least one dose regimen of gefapixant is superior to placebo with respect to the mean change from baseline in awake cough frequency (on the log scale).

Conditions

Refractory Chronic Cough

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Awake Objective Cough Frequency After 12 Weeks of Treatment (Day 84)

  Awake Objective Cough Frequency (per hour) was defined as the total number of cough events during the monitoring period (in general, 24-hr interval) while the participant was awake divided by the total duration (in hours) for the monitoring period that the participant was awake. 24 hour sound recordings were made at Baseline (Study Day -1) and at Week 12 (Day 84) using a digital recording device. An independent cough monitoring center documented the time of each cough event over the 24 hour period, as well as the time when the participant went to sleep and the time the participant woke. Least-squares (LS) mean change from baseline (in log scale) with associated standard error (SE) reported for each treatment group. Change from Baseline in Awake Objective Cough Frequency = (Post-Treatment Awake Cough Frequency minus Baseline Awake Cough Frequency).

  Baseline Visit (Day -1), Day 84

Secondary Outcomes (58)

• Change From Baseline in 24-Hour Objective Cough Frequency After 4 Weeks of Treatment (Day 28)

  Baseline (Study Day -1), Day 28

• Change From Baseline in 24-Hour Objective Cough Frequency After 8 Weeks of Treatment (Day 56)

  Baseline (Study Day -1), Day 56

• Change From Baseline in 24-Hour Objective Cough Frequency After 12 Weeks of Treatment (Day 84)

  Baseline (Study Day -1), Day 84

• Change From Baseline in Awake Objective Cough Frequency After 4 Weeks of Treatment (Day 28)

  Baseline (Study Day -1), Day 28,

• Change From Baseline in Awake Objective Cough Frequency After 8 Weeks of Treatment (Day 56)

  Baseline (Study Day -1), Day 56

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Participants received one matching placebo tablet administered by mouth twice daily for 12 weeks.

Drug: Placebo (for gefapixant)

Gefapixant 7.5 mg

EXPERIMENTAL

Participants received one 7.5 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

Drug: Gefapixant

Gefapixant 20 mg

EXPERIMENTAL

Participants received one 20 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

Drug: Gefapixant

Gefapixant 50 mg

EXPERIMENTAL

Participants received one 50 mg gefapixant tablet administered by mouth twice daily for 12 weeks.

Drug: Gefapixant

Interventions

Gefapixant DRUG

Gefapixant administered as one 7.5 mg, 20 mg, or 50 mg tablet twice daily, depending upon randomization.

Also known as: AF-219, MK-7264

Gefapixant 20 mg; Gefapixant 50 mg; Gefapixant 7.5 mg

Placebo (for gefapixant) DRUG

Also known as: Dose-matched placebo tablet to gefapixant administered twice daily.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women and Men between 18 and 80 years of age inclusive
• Have refractory chronic cough
• Women of child-bearing potential must use 2 forms of acceptable birth control - Have provided written informed consent.
• Are willing and able to comply with all aspects of the protocol

You may not qualify if:

• Current smoker
• Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ratio \<60%
• History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit
• History of opioid use within 1 week of the Baseline Visit
• Body mass index (BMI) \<18 kg/m\^2 or ≥ 40 kg/m\^2
• History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with \<3 excised basal cell carcinomas)
• Screening systolic blood pressure (SBP) \>160 mm Hg or a diastolic blood pressure (DBP) \>90 mm Hg
• Clinically significant abnormal electrocardiogram (ECG) at Screening
• Significantly abnormal laboratory tests at Screening
• Pregnant or Breastfeeding
• Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the participant inappropriate for entry into this trial

Sponsors & Collaborators

• Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA): lead

Related Publications (5)

• Schelfhout J, Nguyen AM, Birring SS, Bacci ED, Vernon M, Muccino DR, La Rosa C, Smith JA. Validation and Meaningful Change Thresholds for an Objective Cough Frequency Measurement in Chronic Cough. Lung. 2022 Dec;200(6):717-724. doi: 10.1007/s00408-022-00587-2. Epub 2022 Nov 8.

  PMID: 36348054 DERIVED

• Nguyen AM, Schelfhout J, Muccino D, Bacci ED, La Rosa C, Vernon M, Birring SS. Leicester Cough Questionnaire validation and clinically important thresholds for change in refractory or unexplained chronic cough. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221099737. doi: 10.1177/17534666221099737.

  PMID: 35614875 DERIVED

• Martin Nguyen A, Bacci ED, Vernon M, Birring SS, Rosa C, Muccino D, Schelfhout J. Validation of a visual analog scale for assessing cough severity in patients with chronic cough. Ther Adv Respir Dis. 2021 Jan-Dec;15:17534666211049743. doi: 10.1177/17534666211049743.

  PMID: 34697975 DERIVED

• Morice AH, Birring SS, Smith JA, McGarvey LP, Schelfhout J, Martin Nguyen A, Xu ZJ, Wu WC, Muccino DR, Sher MR. Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant. Lung. 2021 Apr;199(2):121-129. doi: 10.1007/s00408-021-00437-7. Epub 2021 Apr 7.

  PMID: 33825965 DERIVED

• Smith JA, Kitt MM, Morice AH, Birring SS, McGarvey LP, Sher MR, Li YP, Wu WC, Xu ZJ, Muccino DR, Ford AP; Protocol 012 Investigators. Gefapixant, a P2X3 receptor antagonist, for the treatment of refractory or unexplained chronic cough: a randomised, double-blind, controlled, parallel-group, phase 2b trial. Lancet Respir Med. 2020 Aug;8(8):775-785. doi: 10.1016/S2213-2600(19)30471-0. Epub 2020 Feb 25.

  PMID: 32109425 DERIVED

MeSH Terms

Conditions

Chronic Cough

Interventions

Gefapixant

Condition Hierarchy (Ancestors)

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Afferent Pharmaceuticals Clinical Research

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2015
• First Posted: November 24, 2015
• Study Start: December 15, 2015
• Primary Completion: October 31, 2016
• Study Completion: November 4, 2016
• Last Updated: June 30, 2020
• Results First Posted: February 14, 2018

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share