Effect of Gefapixant (MK-7264/AF-219) on Cough Reflex Sensitivity in Healthy and Chronic Cough Participants (MK-7264-014)

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 100 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02476890

7264-014

2015-002034-47 (EudraCT Number)

MK-7264-014 (Other Identifier)

AF-219-014 (Other Identifier)

Details and patient eligibility

About

The primary objective of this study was to assess the effect of a single dose of gefapixant 100 mg on cough reflex sensitivity to various challenge agents (capsaicin, citric acid, adenosine triphosphate [ATP], and distilled water) in healthy and chronic cough participants.

Full description

The study had a Screening period to determine participant inclusion, two Baseline Visits, and two treatment periods with a minimum 48-hour washout between the treatment periods. At Baseline and during each treatment period, cough sensitivity was measured by standard clinical methodology incorporating four cough challenges. Daytime cough monitoring was performed at Baseline and during each of the two treatment periods (chronic cough participants only).

Enrollment: 36 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 kg/m^2;
• 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;
• Be non-smokers for at least 5 years;
• If a female of child-bearing potential (I. e., have not undergone a hysterectomy or bilateral oophorectomy) or not post-menopausal (defined as no menses for at least 12 months), agree to use 2 forms of acceptable birth control; or if a male, they and/or their partner of child-bearing potential agree to use 2 forms of acceptable birth control;
• Be able to communicate effectively with the Investigator and other study center personnel and agree to comply with the study procedures and restrictions.
• Subjects with chronic cough must have treatment-refractory chronic cough for at least one year, with no objective evidence of an underlying trigger (e. g., asthma)

Exclusion criteria

• History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0);
• Have acute worsening of asthma;
• Do not cough during the ATP or Capsaicin or Citric acid challenge at Screening or only cough twice at the two highest concentrations of the test solution;
• 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;
• Clinically significant abnormal electrocardiogram (ECG) at Screening;
• Significantly abnormal laboratory tests at Screening;
• Pregnant or breastfeeding;
• 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, in the judgment of the Investigator or Sponsor, would make the subject inappropriate for entry into this trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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36 participants in 4 patient groups

Placebo then gefapixant 100 mg/Healthy (Sequence A)

Experimental group

Description:

Healthy participants in Sequence A received a single dose of placebo in treatment Period 1 then a single dose of gefapixant 100 mg in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2.

Treatment:

Drug: Placebo

Drug: Gefapixant 100 mg

Gefapixant 100 mg then placebo/Healthy (Sequence B)

Experimental group

Description:

Healthy participants in Sequence B received a single dose of gefapixant 100 mg in treatment Period 1 then a single dose of placebo in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2.

Treatment:

Drug: Placebo

Drug: Gefapixant 100 mg

Placebo then gefapixant 100 mg/Chronic Cough (Sequence A)

Experimental group

Description:

Chronic Cough participants in Sequence A received a single dose of placebo in treatment Period 1 then a single dose of gefapixant 100 mg in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2.

Treatment:

Drug: Placebo

Drug: Gefapixant 100 mg

Gefapixant 100 mg then placebo/Chronic Cough (Sequence B)

Experimental group

Description:

Chronic Cough participants in Sequence B received a single dose of gefapixant 100 mg in treatment Period 1 then a single dose of placebo in treatment Period 2. There was a minimum 48-hr washout between Periods 1 \& 2.

Treatment:

Drug: Placebo

Drug: Gefapixant 100 mg