Clinical trial NCT02397460: Effect of Gefapixant (AF-219/MK-7264) on Cough Reflex Sensitivity (MK-7264-015)
Official title: A Study to Assess the Effect of AF-219 on Cough Reflex Sensitivity in Both Healthy and Chronic Cough Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Chronic Cough
Lead sponsor: Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2015-03-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)
timeFrame: 2 hours post-dose
measure: Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)
timeFrame: 2 hours post-dose
Secondary outcomes:
measure: Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)
timeFrame: 2 hours post-dose
measure: Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)
timeFrame: 2 hours post-dose
measure: Concentrations of Capsaicin Inducing 2 or More Coughs (C2)
timeFrame: 2 hours post-dose
measure: Concentrations of Capsaicin Inducing 5 or More Coughs (C5)
timeFrame: 2 hours post-dose
measure: Concentrations of ATP Inducing 2 or More Coughs (C2)
timeFrame: 2 hours post-dose
measure: Concentrations of ATP Inducing 5 or More Coughs (C5)
timeFrame: 2 hours post-dose
measure: Urge-to-Cough in Response to Capsaicin Challenge (Chronic Cough Participants Only)
timeFrame: At the end of a 4-hour post-dose observation period on Day 1; at the end of a 24-hour observation period on Day 2
measure: Urge-to-Cough in Response to ATP Challenge (Chronic Cough Participants Only)
timeFrame: At the end of a 4-hour post-dose observation period on Day 1; at the end of a 24-hour observation period on Day 2
measure: Cough Severity in Response to Capsaicin Challenge (Chronic Cough Participants Only)
timeFrame: At the end of a 4-hour post-dose observation period; at the end of a 24-hour observation period on Day 2
measure: Cough Severity in Response to ATP Challenge (Chronic Cough Participants Only)
timeFrame: At the end of a 4-hour post-dose observation period on Day 1; at the end of a 24-hour observation period on Day 2
measure: Daytime Cough Frequency in Participants With Chronic Cough Who Underwent Capsaicin Challenge
timeFrame: From start of challenge (2 hours post-dose) to bedtime; up to 12 hours
measure: Daytime Cough Frequency in Participants With Chronic Cough Who Underwent ATP Challenge
timeFrame: From start of challenge (2 hours post-dose) to bedtime; up to 12 hours
measure: Percentage of Participants Who Experienced at Least One Adverse Event
timeFrame: Up to Day 41
measure: Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
timeFrame: Up to Day 24
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: The Medicines Evaluation Unit
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: