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

NCT ID: NCT02502097

Last Updated: 2021-05-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-26
• Study Completion Date: 2016-07-14

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.

Detailed Description

Prior to Amendment 3, participants were randomized to receive either placebo twice daily (BID) for 14 days during Period 1 followed by gefapixant 50 mg BID for 10 days then gefapixant 150 mg BID for 4 days BID during Period 2; or gefapixant 50 mg BID for 10 days then gefapixant 150 mg BID for 4 days during Period 1, followed by placebo BID for 14 days during Period 2. Each period was separated by a 14 to 21-day washout period.

During Amendment 3, participants were randomized to receive either placebo BID for 14 days during Period 1 followed by gefapixant 50 mg BID for 14 days during Period 2; or gefapixant 50 mg BID for 14 days during Period 1, followed by placebo BID for 14 days during Period 2. Each period was separated by a 14 to 21-day washout period.

Conditions

Idiopathic Pulmonary Fibrosis; Cough

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Gefapixant>Placebo Pre-Amendment 3

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

Group Type: EXPERIMENTAL

Gefapixant

Intervention Type: DRUG

Gefapixant 50 mg tablet, administered by mouth

Placebo

Intervention Type: OTHER

Matching placebo to gefapixant, tablet administered by mouth

Placebo>Gefapixant Pre-Amendment 3

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

Group Type: EXPERIMENTAL

Gefapixant

Intervention Type: DRUG

Gefapixant 50 mg tablet, administered by mouth

Placebo

Intervention Type: OTHER

Matching placebo to gefapixant, tablet administered by mouth

Gefapixant>Placebo Post-Amendment 3

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

Group Type: EXPERIMENTAL

Gefapixant

Intervention Type: DRUG

Gefapixant 50 mg tablet, administered by mouth

Placebo

Intervention Type: OTHER

Matching placebo to gefapixant, tablet administered by mouth

Placebo>Gefapixant Post-Amendment 3

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

Group Type: EXPERIMENTAL

Gefapixant

Intervention Type: DRUG

Gefapixant 50 mg tablet, administered by mouth

Placebo

Intervention Type: OTHER

Matching placebo to gefapixant, tablet administered by mouth

Interventions

Gefapixant

Gefapixant 50 mg tablet, administered by mouth

Intervention Type: DRUG

Placebo

Matching placebo to gefapixant, tablet administered by mouth

Intervention Type: OTHER

Other Intervention Names

AF-219; MK-7264

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Treatment with an investigational drug or biologic within 30 days preceding the first dose of study medication or plans to take another investigational drug or biologic within 30 days of study completion
• Blood donation within 56 days or plasma donation within 7 days prior to dosing
• 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

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: DERIVED

PMID: 34152585 (View on PubMed)

Other Identifiers

AF-219-016

Identifier Type: OTHER

Identifier Source: secondary_id

MK-7264-016

Identifier Type: OTHER

Identifier Source: secondary_id

7264-016

Identifier Type: -

Identifier Source: org_study_id