A Study to Evaluate the Effect of Gefapixant (AF-219/MK-7264) on Methacholine Hyper-reactivity in Participants With Asthma (MK-7264-009)

NCT01993329 | Completed Phase 2 Results

• 4 other identifiers: 7264-009AF219-0092013-003566-13MK-7264-009
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a randomized, double-blind, double-dummy, placebo-controlled, three-way cross-over, single centre study in participants with asthma undergoing inhalation of methacholine and adenosine triphosphate (ATP) to assess the provocative concentration (PC20) response of two dose levels of gefapixant (AF-219) compared with placebo.

Conditions

Asthma

Outcome Measures

Primary Outcomes (1)

• Provocative Concentration (PC20) After Methacholine Challenge

  The provocative concentration (PC) of inhaled methacholine required to reduce forced expiratory volume in 1 second (FEV1) by 20% (PC20) was calculated from the methacholine challenge at screening and 2 hours (+15 minutes) post dose on Day 3 of each Treatment Period using a five-breath dosimeter method. The primary endpoint was the methacholine PC20 value normalized by means of a log (base 2) transformation, at 2 dose levels compared with placebo in participants with asthma following provocation with methacholine.

  Screening (Day -21 to Day -1) and Day 3

Secondary Outcomes (1)

• Highest FEV1 After Methacholine Challenge

  Screening (Day -21 to Day -1) and Day 3

Study Arms (6)

Gefapixant 50/ Gefapixant 300/ Placebo

EXPERIMENTAL

Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.

Drug: Gefapixant 50 mg; Drug: Gefapixant 300 mg; Drug: Placebo to mimic 50 mg tablets; Drug: Placebo to mimic 300 mg tablets

Gefapixant 50/ Placebo/ Gefapixant 300

EXPERIMENTAL

Gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.

Drug: Gefapixant 50 mg; Drug: Gefapixant 300 mg; Drug: Placebo to mimic 50 mg tablets; Drug: Placebo to mimic 300 mg tablets

Gefapixant 300/ Gefapixant 50/ Placebo

EXPERIMENTAL

Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.

Drug: Gefapixant 50 mg; Drug: Gefapixant 300 mg; Drug: Placebo to mimic 50 mg tablets; Drug: Placebo to mimic 300 mg tablets

Gefapixant 300/ Placebo/ Gefapixant 50

EXPERIMENTAL

Gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 1, placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.

Drug: Gefapixant 50 mg; Drug: Gefapixant 300 mg; Drug: Placebo to mimic 50 mg tablets; Drug: Placebo to mimic 300 mg tablets

Placebo/ Gefapixant 50/ Gefapixant 300

EXPERIMENTAL

Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 2, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.

Drug: Gefapixant 50 mg; Drug: Gefapixant 300 mg; Drug: Placebo to mimic 50 mg tablets; Drug: Placebo to mimic 300 mg tablets

Placebo/ Gefapixant 300/ Gefapixant 50

EXPERIMENTAL

Placebo to match gefapixant 50 mg and placebo to match gefapixant 300 mg twice daily for 3.5 days during Period 1, gefapixant 300 mg and placebo (for gefapixant 50 mg) twice daily for 3.5 days during Period 2, gefapixant 50 mg and placebo (for gefapixant 300 mg) twice daily for 3.5 days during Period 3. Each period is separated by at least a 7-day wash-out period.

Drug: Gefapixant 50 mg; Drug: Gefapixant 300 mg; Drug: Placebo to mimic 50 mg tablets; Drug: Placebo to mimic 300 mg tablets

Interventions

Gefapixant 50 mg DRUG

Gefapixant 50 mg tablet administered orally

Also known as: AF-219, MK-7264

Gefapixant 300/ Gefapixant 50/ Placebo; Gefapixant 300/ Placebo/ Gefapixant 50; Gefapixant 50/ Gefapixant 300/ Placebo; Gefapixant 50/ Placebo/ Gefapixant 300; Placebo/ Gefapixant 300/ Gefapixant 50; Placebo/ Gefapixant 50/ Gefapixant 300

Gefapixant 300 mg DRUG

Gefapixant 300 mg tablet administered orally

Also known as: AF-219, MK-7264

Gefapixant 300/ Gefapixant 50/ Placebo; Gefapixant 300/ Placebo/ Gefapixant 50; Gefapixant 50/ Gefapixant 300/ Placebo; Gefapixant 50/ Placebo/ Gefapixant 300; Placebo/ Gefapixant 300/ Gefapixant 50; Placebo/ Gefapixant 50/ Gefapixant 300

Placebo to mimic 50 mg tablets DRUG

Sugar pill manufactured to mimic gefapixant 50 mg tablets

Gefapixant 300/ Gefapixant 50/ Placebo; Gefapixant 300/ Placebo/ Gefapixant 50; Gefapixant 50/ Gefapixant 300/ Placebo; Gefapixant 50/ Placebo/ Gefapixant 300; Placebo/ Gefapixant 300/ Gefapixant 50; Placebo/ Gefapixant 50/ Gefapixant 300

Placebo to mimic 300 mg tablets DRUG

Sugar pill manufactured to mimic gefapixant 300 mg tablets

Gefapixant 300/ Gefapixant 50/ Placebo; Gefapixant 300/ Placebo/ Gefapixant 50; Gefapixant 50/ Gefapixant 300/ Placebo; Gefapixant 50/ Placebo/ Gefapixant 300; Placebo/ Gefapixant 300/ Gefapixant 50; Placebo/ Gefapixant 50/ Gefapixant 300

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women of child-bearing potential (WOCBP) (i.e., women who are not surgically sterile, not having had hysterectomy, bilateral tubal occlusion or bilateral oophorectomy, or are not postmenopausal) must have a negative pregnancy test at Screening and prior to randomization. WOCBP must be using 2 forms of acceptable birth control method from Screening through the Follow-Up Visit. Acceptable birth control methods include (of which 2 must be used):
• Established use of oral, injected or implanted hormonal methods of contraception
• Intrauterine device (IUD) or intrauterine system (IUS)
• Condom with spermicide
• Diaphragm with spermicide
• Double-barrier method (diaphragm for female participant and condom for male partner with spermicidal) satisfies the requirement for 2 forms of acceptable birth control. When in line with the preferred lifestyle of the participant, true and complete abstinence (not periodic abstinence) is acceptable.
• Non-smokers or former smokers, who stopped smoking 6 months prior to screening. Former smokers should not have a smoking history of more than 5 pack years (1 pack of 20 cigarettes per day over 5 years).
• Physician documented history or diagnosis of asthma for at least 6 months prior to screening according to the Global Initiative in Asthma guidelines (GINA, 2012).
• Requires the use of Short acting β2-agonist therapy only (≤ 8 puffs per day) for at least 4 weeks prior to screening and prior to randomization.

You may not qualify if:

• Has been hospitalized or attended the emergency department for an asthma attack in the 12 months prior to screening.
• Exacerbation of asthma or lower respiratory tract infection during the 4 weeks before screening or prior to randomization.
• Upper respiratory tract infection during the 4 weeks before screening or prior to randomization requiring treatment with antibiotics.
• Inhaled or systemic corticosteroids (oral, intravenous, intramuscular) within 4 weeks prior to screening or prior to randomization.
• Short-acting or long-acting antihistamines within 48hrs or 7 days, respectively, prior to screening.
• Body mass index (BMI) \<18 kg/m2 or ≥ 35 kg/m2 at screening.
• History of kidney/bladder stones (nephro/uro-lithiasis) within 5 years of screening.
• History of conditions or disorders that predispose to nephrolithiasis, such as Type 1 renal tubular acidosis, cystinuria, gout, hyperparathyroidism, inflammatory bowel disease (i.e., ulcerative colitis and Crohn's disease), short bowel syndrome, or bariatric surgery.
• History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including participants with basal cell carcinomas or cervical carcinoma in situ that has been successfully treated surgically).
• Personal or family history of congenital long QT Interval on ECG (QT) syndrome.
• Presence of a cardiac pacemaker.
• History of a diagnosis of drug or alcohol dependency or abuse within approximately the last 3 years.
• Diagnosis of depression, psychosis, bipolar disorder, or schizoaffective disorder.
• Participants with diabetes Type I or uncontrolled diabetes Type II or Glycosylated Hemoglobin (HbA1c) \> 8.0% at screening.
• Any condition possibly affecting drug absorption e.g., gastrectomy, gastroplasty, any type of bariatric surgery, vagotomy, or bowel resection.

Sponsors & Collaborators

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

MeSH Terms

Conditions

Asthma

Interventions

Gefapixant

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

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

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

  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: November 15, 2013
• First Posted: November 25, 2013
• Study Start: December 16, 2013
• Primary Completion: February 20, 2014
• Study Completion: February 28, 2014
• Last Updated: February 3, 2021
• Results First Posted: February 3, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will share