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

Refractory Chronic Cough Clinical Trial

Official title:

A Study to Assess the Effect of MK-7264 (AF-219) on Cough Reflex Sensitivity in Both Healthy and Chronic Cough Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03407014
• Other study ID #: 7264-014
• Secondary ID: MK-7264-014AF-21
• Status: Completed
• Phase: Phase 2
• First received: January 16, 2018
• Last updated: January 16, 2018
• Start date: October 28, 2015
• Est. completion date: October 20, 2016

Study information

• Verified date: January 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: October 20, 2016
• Est. primary completion date: October 20, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cough
• Refractory Chronic Cough

Intervention

Drug:
• Gefapixant 100 mg
Gefapixant 100 mg (2 x 50 mg tablets), administered orally as a single dose in treatment Period 1 or treatment Period 2
• Placebo
Placebo (two tablets matching gefapixant 50 mg), administered orally as a single dose in treatment Period 1 or treatment Period 2

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cough Reflex Sensitivity to Capsaicin in Participants Who Received Gefapixant 100 mg and Placebo	The concentration of capsaicin inducing at least 2 coughs (C2) and 5 coughs (C5), averaged across 3 time points (at 1, 3, and 5 hours post-dose) on the treatment days were assessed in healthy and chronic cough participants.	5 hours
Primary	Cough Reflex Sensitivity to Citric Acid in Participants Who Received Gefapixant 100 mg and Placebo	The concentration of citric acid inducing at least 2 coughs (C2) and 5 coughs (C5), averaged across 3 time points (at 1, 3, and 5 hours post-dose) on the treatment days were assessed in healthy and chronic cough participants.	5 hours
Primary	Cough Reflex Sensitivity to ATP in Participants Who Received Gefapixant 100 mg and Placebo	The concentration of ATP inducing at least 2 coughs (C2) and 5 coughs (C5), averaged across 3 time points (at 1, 3, and 5 hours post-dose) on the treatment days were assessed in healthy and chronic cough participants.	5 hours
Primary	Cough Reflex Sensitivity to Distilled Water in Participants Who Received Gefapixant 100 mg and Placebo	The concentration of distilled water inducing at least 2 coughs (C2) and 5 coughs (C5), averaged across 3 time points (at 1, 3, and 5 hours post-dose) on the treatment days were assessed in healthy and chronic cough participants.	5 hours
Secondary	Change From Baseline in Cough Severity Visual Analogue Scale (VAS) After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only)	Chronic cough participants completed a 100mm VAS to record their cough severity from 'No Cough' (0) up to 'Worst Cough' (100).	1 day
Secondary	Change From Baseline in Urge to Cough VAS After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only)	Chronic cough participants completed a 100mm VAS to record the severity of their urge to cough as 'No urge-to-cough' (0) and 'Worst urge-to-cough' (100).	1 day
Secondary	Change From Baseline in Cough Frequency After Cough Challenge Testing in Participants Who Received Gefapixant 100 mg and Placebo (Chronic Cough Participants Only)	An ambulatory cough recording device recorded all sounds the participant made during cough monitoring to measure the change from baseline in objective cough frequency on the treatment days.	24 hours
Secondary	Percentage of Participants Who Experienced One or More Adverse Events During Study Treatment and Follow Up	The percentage of participants receiving gefapixant 100 mg or placebo who had at least 1 adverse event (AE) during the treatment periods (including washout periods) in addition to 14 days (+3 days) until a post-treatment follow-up visit.	18 days
Secondary	Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event		4 days