A Dose Escalation Study of Gefapixant (AF-219/MK-7264) in Refractory Chronic Cough (MK-7264-010)

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

Status and phase: Completed; Phase 2

Conditions: Refractory Chronic Cough

Treatments: Drug: Gefapixant; Drug: Placebo (for gefapixant)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02349425

2015-000474-35 (Other Identifier)

MK-7264-010 (Other Identifier)

AF219-010 (Other Identifier)

7264-010

Details and patient eligibility

About

A randomized, double-blind, placebo-controlled, crossover, dose escalation study to assess the efficacy and tolerability of gefapixant (AF-219; MK-7264) in participants with refractory chronic cough.

Enrollment: 59 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Chest radiograph or computed tomography (CT) thorax within the last 12 months not demonstrating any abnormality considered to be significantly contributing to the chronic cough
• Refractory chronic cough for at least one year: a cough that is unresponsive to at least 8 weeks of targeted treatment for identified underlying triggers including reflux disease, asthma and post-nasal drip or unexplained cough: a cough for which no objective evidence of an underlying trigger can be determined after investigation
• Score of ≥ 40 mm on the Cough Severity Visual Analog 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 participants 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
• Individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history
• Treatment with an angiotensin converting enzyme (ACE)-inhibitor as the potential cause of a participant's cough, or requiring treatment with an ACE-inhibitor during the study or within 4 weeks prior to the Baseline Visit (Day 0)
• Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 60%
• History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0)
• History of opioid use within 1 week of the Baseline Visit (Day 0)
• Requiring concomitant therapy with prohibited medications
• Body mass index (BMI) <18 kg/m^2 or ≥ 37 kg/m^2
• History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including participants 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)
• Screening systolic blood pressure (SBP) >160 mmHg or a diastolic blood pressure (DBP) >90 mmHg
• Clinically significant abnormal electrocardiogram (ECG) at Screening
• Personal or family history of congenital long QT syndrome or family history of sudden death
• Cardiac pacemaker
• Significantly abnormal laboratory tests at Screening
• Breastfeeding
• Treatment with an investigational drug (except gefapixant) or biologic within 60 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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59 participants in 4 patient groups

Cohort 1: Gefapixant>Placebo

Experimental group

Description:

50, 100, 150, and 200 mg gefapixant twice daily (BID) for 4 days each in Period 1 and placebo BID for 16 days in Period 2. For Cohort 1, there was a 3 to 7 day washout period between treatment periods.

Treatment:

Drug: Gefapixant

Drug: Placebo (for gefapixant)

Cohort 1: Placebo>Gefapixant

Experimental group

Description:

Placebo BID for 16 days in Period 1 and gefapixant 50, 100, 150, and 200 mg BID for 4 days each in Period 2. For Cohort 1, there was a 3 to 7 day washout period between treatment periods.

Treatment:

Drug: Gefapixant

Drug: Placebo (for gefapixant)

Cohort 2: Gefapixant>Placebo

Experimental group

Description:

Gefapixant 7.5, 15, 30, and 50 mg BID for 4 days each in Period 1 and placebo BID for 16 days in Period 2. For Cohort 2, there was a 14 to 21 day washout period between treatment periods.

Treatment:

Drug: Gefapixant

Drug: Placebo (for gefapixant)

Cohort 2: Placebo>Gefapixant

Experimental group

Description:

Placebo BID for 16 days in Period 1 and gefapixant 7.5, 15, 30, and 50 mg BID for 4 days each in Period 2. For Cohort 2, there was a 14 to 21 day washout period between treatment periods.

Treatment:

Drug: Gefapixant

Drug: Placebo (for gefapixant)