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

A Randomized Placebo-Controlled Study to Assess the Efficacy and Safety of AF-219, a P2X3 Receptor Antagonist, in Subjects With Idiopathic Pulmonary Fibrosis (IPF) With Persistent Cough

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

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.

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