Effect of Gefapixant (AF-219/MK-7264) on Cough Reflex Sensitivity (MK-7264-015)

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: Placebo; Drug: Gefapixant

Study type: Interventional

Funder types: Industry

Identifiers

NCT02397460

MK-7264-015 (Other Identifier)

7264-015

AF-219-015 (Other Identifier)

2015-000464-34 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this double-blind crossover study is to assess the effect of single doses of 50 mg and 300 mg gefapixant (AF-219/MK-7264) on cough reflex sensitivity to capsaicin in both healthy participants and participants with chronic cough. This study will also assess the effect of single doses of gefapixant on cough reflex sensitivity to adenosine triphosphate (ATP) in healthy participants and participants with chronic cough.

Full description

Up to 30 participants (male and female) who meet all entry criteria will be randomly assigned to treatment with gefapixant or matching placebo.

There will be a Screening Period, a Baseline Visit (cough participants only), and four Treatment Periods, with a washout period between treatments. Participants will return after their last Treatment Visit for a Follow-up Visit.

At the Screening Visit and during the Treatment Periods, cough sensitivity will be measured by standard clinical methodology incorporating two cough challenges: 1) capsaicin; 2) ATP. The ATP challenge will only be performed during the study treatment period. The Baseline Visit (cough participants only) will occur prior to Treatment Period 1. Daytime cough monitoring will be performed at the Baseline Visit and during each of the four Treatment Periods (cough participants only).

Enrollment: 50 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Have provided written informed voluntary consent;
• Be able to speak, read, and understand English;
• Be males or females, of any race, between 18 and 80 years of age, inclusive;
• Have a body mass index (BMI) ≥18 and <35.0 kg/m2;
• Be in good general health with no clinically relevant abnormalities based on the medical history, physical examination, clinical laboratory evaluations (hematology, clinical chemistry, and urinalysis), and 12 lead electrocardiogram;
• Women of child bearing potential must have a negative pregnancy test at Screening and prior to randomization.
• Women of child-bearing potential must use 2 methods of acceptable birth control from Screening until 3 months after the last dose of study drug;
• Male subjects with partners of child-bearing potential (as defined in Inclusion No. 8) must use 2 methods of acceptable birth control, 1 of which must be a barrier method;
• Subjects with chronic cough
• Be able to communicate effectively with the Investigator and other study center personnel and agree to comply with the study procedures and restrictions

Exclusion criteria

• Current smoker;
• Individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history(chronic cough subjects), or >10 pack-year smoking history (healthy subjects);
• History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks prior to Screening or prior to randomization;
• History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (with the exception of < 3 excised basal cell carcinomas);
• History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years;
• In the opinion of the Principal Investigator, an uncontrolled or unstable clinically significant neurological, psychiatric, respiratory, cardiovascular, peripheral vascular, gastrointestinal, hepatic, pancreatic, endocrinological, hematological, or immunological disorder or an active infection;
• Clinically significant abnormal electrocardiogram (ECG) at Screening
• Significantly abnormal laboratory tests at Screening
• Breastfeeding;
• In the judgement of the Principal Investigator, 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 would make the subject inappropriate for entry into this trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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50 participants in 3 patient groups, including a placebo group

Gefapixant 50 mg

Experimental group

Description:

Gefapixant 50 mg (1 tablet) administered as a single dose

Treatment:

Drug: Gefapixant

Gefapixant 300 mg

Experimental group

Description:

Gefapixant 300 mg (6 tablets) administered as a single dose

Treatment:

Drug: Gefapixant

Placebo

Placebo Comparator group

Description:

Placebo-matching tablets administered as a single dose

Treatment:

Drug: Placebo