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

NCT02397460 | Completed Phase 2 Results

• 4 other identifiers: 7264-015AF-219-015MK-7264-0152015-000464-34
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Refractory Chronic Cough

Outcome Measures

Primary Outcomes (2)

• Cough Reflex Sensitivity to Capsaicin Measured by Maximal Cough Response (Emax)

  The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with capsaicin was assessed in male and female healthy participants and participants with chronic cough. Capsaicin-evoked cough challenge was performed 2 hours post-dose in Periods 1 and 2. The maximal cough response (Emax) to capsaicin was assessed. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation. The number of explosive cough sounds occurring within the first 15 seconds after inhalation were recorded. Nonlinear mixed-effects modeling was used to estimate the Emax. Population pharmacodynamic modeling was performed in NONMEM 7.3. Data exploration, goodness-of-fit plots, statistical analyses, and simulations were performed in Matlab R2015a. Note: All values presented in this table are model-based.

  2 hours post-dose

• Cough Reflex Sensitivity to Capsaicin Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)

  The effect of single doses of 50 mg and 300 mg gefapixant on cough reflex sensitivity to challenge with capsaicin was assessed in male and female healthy participants and participants with chronic cough. Capsaicin-evoked cough challenge was performed 2 hours post-dose in Periods 1 and 2. The concentration of capsaicin required to induce 50% of the Emax (ED50) was assessed. For capsaicin challenge, doubling concentrations from 0.49 μM to 1000 μM were prepared by dilution of stock solutions with saline, and were administered by inhalation. Nonlinear mixed-effects modeling was used to estimate the ED50. Population pharmacodynamic modeling was performed in NONMEM 7.3 using Laplace estimation method. Data exploration, goodness-of-fit plots, statistical analyses, and simulations were performed in Matlab R2015a. Note: All values presented in this table are model-based.

  2 hours post-dose

Secondary Outcomes (14)

• Cough Reflex Sensitivity to Adenosine Triphosphate (ATP) Measured by Maximal Cough Response (Emax)

  2 hours post-dose

• Cough Reflex Sensitivity to ATP Measured by the Tussive Concentration Required to Achieve 50% of Emax (ED50)

  2 hours post-dose

• Concentrations of Capsaicin Inducing 2 or More Coughs (C2)

  2 hours post-dose

• Concentrations of Capsaicin Inducing 5 or More Coughs (C5)

  2 hours post-dose

• Concentrations of ATP Inducing 2 or More Coughs (C2)

  2 hours post-dose

Study Arms (3)

Gefapixant 50 mg

EXPERIMENTAL

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

Drug: Gefapixant

Gefapixant 300 mg

EXPERIMENTAL

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

Drug: Gefapixant

Placebo

PLACEBO COMPARATOR

Placebo-matching tablets administered as a single dose

Drug: Placebo

Interventions

Gefapixant DRUG

Gefapixant tablets administered orally as a single dose of 50 mg (1 tablet) or 300 mg (6 tablets)

Also known as: AF-219, MK-7264

Gefapixant 300 mg; Gefapixant 50 mg

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

The Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Chronic Cough

Interventions

Gefapixant

Condition Hierarchy (Ancestors)

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2015
• First Posted: March 25, 2015
• Study Start: April 29, 2015
• Primary Completion: April 22, 2016
• Study Completion: May 16, 2016
• Last Updated: February 12, 2021
• Results First Posted: February 12, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)