A Study of Gefapixant (AF-219/MK-7264) in Participants With Idiopathic Pulmonary Fibrosis (IPF) With Persistent Cough (MK-7264-016)

NCT02502097 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 7264-016AF-219-016MK-7264-016
• Study Type: interventional
• Target: 51
• Locations: 0 countries
• Sites: N/A

Brief Summary

A randomized, double-blind, placebo-controlled, crossover, dose escalation study of gefapixant (AF-219) in participants with Idiopathic Pulmonary Fibrosis (IPF) with persistent cough.

Conditions

Idiopathic Pulmonary Fibrosis; Cough

Outcome Measures

Primary Outcomes (4)

• Mixed Model of Repeated Measures (MMRM) Change From Baseline in Awake Objective Cough Frequency (Periods 1 & 2 Combined)

  Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the results of the 2-period cross-over study. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative change indicates a decrease in cough frequency, while a positive change indicates an increase in cough frequency.

  Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

• Awake Objective Cough Frequency (Periods 1 & 2 Combined)

  Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period.

  Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

• Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)

  Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0 (baseline), and after administration of the study drug on Day 7 and Day 14 in Periods 1 and 2. The cough frequency is the coughs/hour over each 24-hour period. Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Baseline cough frequency was derived from the cough monitoring performed at the beginning of each treatment period while the post-treatment cough frequency was derived from the cough monitoring performed at the end of the dosing period. A negative value indicates a decrease in cough frequency.

  Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

• Percent Change From Baseline of Awake Objective Cough Frequency (Periods 1 & 2 Combined)

  Awake objective cough frequency was defined as the total number of cough events during the monitoring period the participant was awake divided by the total duration for the monitoring period the participant was awake. Percent change from baseline in awake objective cough frequency (0-6 hours after the morning dose) was reported at each dosing interval. Percent change in awake cough frequency = 100 X (post treatment cough frequency - baseline cough frequency) divided by the baseline cough frequency. A negative value indicates a decrease in cough frequency.

  Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Secondary Outcomes (22)

• MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 1)

  Baseline (Day 0), Day 7, and Day 14 (Period 1)

• MMRM Analysis of Change From Baseline in Awake Objective Cough Frequency (Period 2)

  Baseline (Day 0), Day 7, and Day 14 (Period 2)

• Responder Analysis of Awake Cough Frequency at Day 7 (Periods 1 & 2 Combined)

  Day 7 (Period 1 and Period 2)

• Responder Analysis of Awake Cough Frequency at Day 14 (Periods 1 & 2 Combined)

  Day 14 (Period 1 and Period 2)

• MMRM Analysis of Change From Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)

  Baseline (Day 0), Day 7, and Day 14 (Period 1 and Period 2)

Other Outcomes (10)

• Pre-dose Baseline of Awake Objective Cough Frequency

  Baseline (Day 0) (Period 1 and Period 2)

• Pre-dose Baseline 24-hour Objective Cough Frequency (Periods 1 & 2 Combined)

  Baseline (Day 0) (Period 1 and Period 2)

• Pre-dose Baseline of 24-hour Objective Cough Frequency (Period 1)

  Baseline (Day 0) (Period 1)

Study Arms (4)

Gefapixant>Placebo Pre-Amendment 3

EXPERIMENTAL

Gefapixant 50 mg twice daily (BID) for 10 days, then 150 mg BID for 4 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2

Drug: Gefapixant; Other: Placebo

Placebo>Gefapixant Pre-Amendment 3

EXPERIMENTAL

Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 10 days, then 150 mg for 4 days in Period 2

Drug: Gefapixant; Other: Placebo

Gefapixant>Placebo Post-Amendment 3

EXPERIMENTAL

Gefapixant 50 mg twice daily (BID) for 14 days in Period 1, followed by a 14-21 day washout period, then placebo BID for 14 days in Period 2

Drug: Gefapixant; Other: Placebo

Placebo>Gefapixant Post-Amendment 3

EXPERIMENTAL

Placebo BID for 14 days in Period 1, followed by a 14-21 day washout period, then gefapixant 50 mg BID for 14 days in Period 2

Drug: Gefapixant; Other: Placebo

Interventions

Gefapixant DRUG

Gefapixant 50 mg tablet, administered by mouth

Also known as: AF-219, MK-7264

Gefapixant>Placebo Post-Amendment 3; Gefapixant>Placebo Pre-Amendment 3; Placebo>Gefapixant Post-Amendment 3; Placebo>Gefapixant Pre-Amendment 3

Placebo OTHER

Matching placebo to gefapixant, tablet administered by mouth

Gefapixant>Placebo Post-Amendment 3; Gefapixant>Placebo Pre-Amendment 3; Placebo>Gefapixant Post-Amendment 3; Placebo>Gefapixant Pre-Amendment 3

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Idiopathic pulmonary fibrosis diagnosis based upon the American Thoracic Society (ATS)/ European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/ Latin American Thoracic Society (ALAT) IPF 2011 guideline
• Life expectancy of greater than 6 months
• Stable medical condition (IPF) for at least 4 weeks
• Self-reported history of troublesome daily cough for more than 8 weeks
• Score of ≥ 40mm on the Cough Severity Visual Analogue Scale (VAS) at Screening
• Women of child-bearing potential must use 2 forms of acceptable birth control method from Screening through the Follow-Up Visit
• Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control from Screening until 3 months after the last dose of study drug
• Written informed consent
• Willing and able to comply with all aspects of the protocol

You may not qualify if:

• Current smoker (i.e., within the last 30 days).
• Initiation of treatment with an ACE-inhibitor within 4 weeks prior to the Baseline Visit (Day 0) or during the study
• History of upper and/or lower respiratory tract infection within 4 weeks of the Baseline Visit (Day 0)
• History of opioid use for treatment of cough within 1 week of the Baseline Visit (Day 0)
• Requiring prohibited medications
• Body mass index (BMI) \<18 kg/m\^2 or ≥ 40 kg/m\^2
• History or symptoms of renal disease or renal obstructive disease
• History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including subjects with \<3 excised basal cell carcinomas)
• History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years
• Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty, any type of bariatric surgery, vagotomy, or bowel resection)
• Recent history of stroke or transient ischemic attack (within 6 months prior to Screening) not due to trauma, repaired vascular malformation, or aneurysm
• Screening systolic blood pressure (SBP) \>160 mm Hg or a diastolic blood pressure (DBP) \>90 mm Hg
• QTc interval \>450 milliseconds in males, \>470 milliseconds in females
• Significantly abnormal laboratory tests at Screening
• Breastfeeding

Sponsors & Collaborators

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

Related Publications (1)

• Martinez FJ, Afzal AS, Smith JA, Ford AP, Li JJ, Li Y, Kitt MM; Chronic Cough in IPF Study Group. Treatment of Persistent Cough in Subjects with Idiopathic Pulmonary Fibrosis (IPF) with Gefapixant, a P2X3 Antagonist, in a Randomized, Placebo-Controlled Clinical Trial. Pulm Ther. 2021 Dec;7(2):471-486. doi: 10.1007/s41030-021-00162-9. Epub 2021 Jun 21.

  PMID: 34152585 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Cough

Interventions

Gefapixant

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; 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

• Medical Director

  Merck Sharp & Dohme LLC

  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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2015
• First Posted: July 20, 2015
• Study Start: August 26, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 14, 2016
• Last Updated: May 26, 2021
• Results First Posted: May 26, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share