The Pharmacokinetics of Gefapixant (MK-7264) in Participants With Renal Insufficiency (MK-7264-026)

NCT ID: NCT03108924

Last Updated: 2022-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-14
• Study Completion Date: 2017-09-13

Brief Summary

This trial aims to evaluate the plasma pharmacokinetics of gefapixant (MK-7264) administered to participants with varying degrees of renal insufficiency (RI) compared to healthy matched controls; and to investigate the extent of MK-7264 removal by hemodialysis (HD) in participants with end stage renal disease (ESRD), following administration of a single 50 mg dose of gefapixant.

Conditions

Renal Insufficiency

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Moderate RI

Participants with moderate renal insufficiency (RI) are treated with a single 50 mg dose of gefapixant

Group Type: EXPERIMENTAL

Gefapixant

Intervention Type: DRUG

After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.

Severe RI

Participants with severe RI are treated with a single 50 mg dose of gefapixant

Group Type: EXPERIMENTAL

Gefapixant

Intervention Type: DRUG

After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.

Healthy Matched Controls

Healthy, participants matched for age and body weight are treated with a single 50 mg dose of gefapixant

Group Type: OTHER

Gefapixant

Intervention Type: DRUG

After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.

ESRD Requiring HD

Participants with end stage renal disease (ESRD) requiring hemodialysis (HD), are treated in Period 1 with a single 50 mg dose of gefapixant immediately after the scheduled HD, followed in Period 2 with a single 50 mg dose of gefapixant two hours prior to HD. Between the Periods 1 and 2 MK-7264 dose administrations there was approximately a 7-day washout period with 3 dialysis sessions.

Group Type: EXPERIMENTAL

Gefapixant

Intervention Type: DRUG

After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.

Interventions

Gefapixant

After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.

Intervention Type: DRUG

Other Intervention Names

MK-7264

Eligibility Criteria

Inclusion Criteria

• Is a non-smoker or moderate smoker (≤ 20 cigarettes/day or the equivalent) who agrees to consume no more than 10 cigarettes or equivalent/day from the time of screening and throughout the period of sample collection.
• Has a body mass index (BMI) ≥ 18.5 and ≤ 40.0 kg/m^2,
• Is judged to be in good health based on medical history, physical examination, vital signs, and laboratory safety tests. Has no clinically significant electrocardiogram (ECG) abnormality, as deemed by the Investigator.
• Females are non-pregnant, and non-breast feeding. If female with reproductive potential, they must demonstrate they are not pregnant and agree to use (and/or have their partner use) two (2) acceptable methods of birth control beginning at screening, throughout the study and until 2 weeks after dosing of study drug.
• Participants with ESRD requiring HD has been maintained on stable regimen of thrice-weekly HD for at least 3 months prior to first dosing.
• Healthy participants, must be within ± 10 years of the mean age of participants with RI; and must be within ± 10 kg of the mean weight of participants with RI.

Exclusion Criteria

• Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit, or expected during the conduct of the study.
• Has a history or presence of clinically significant medical or psychiatric condition or disease.
• Has a history of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk by participating in the study.
• Has a history or presence of alcoholism or drug abuse within the past 6 months prior to dosing.
• Has a history or presence of hypersensitivity or idiosyncratic reaction to the study drug or related compounds (including sulfonamides).
• Has a history or presence of renal artery stenosis; or major risk factors for renal/urinary calculi.
• Has rapidly fluctuating renal function as determined by historical measurements.
• Female who is pregnant, or lactating.
• Has positive results for urine or saliva drug and/or urine or breath alcohol at screening or check-in.
• Is positive at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).
• Has positive macroscopic hematuria or crystalluria at screening or check-in.
• Is unable to refrain from or anticipates using any medication or substance including prescription or over-the-counter, vitamin supplements, natural or herbal supplements.
• Has been on a diet incompatible with the on-study diet, within the 28 days prior to dosing.
• Has donated blood or had significant blood loss within 56 days prior to dosing.
• Has donated plasma within 7 days prior to dosing.
• Has taken gefapixant at any time prior to dosing on the current study.
• Has participated in another clinical trial within 28 days prior to dosing based on the latest blood collection or dosing.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Clinical Pharmacology of Miami ( Site 0001)

Hialeah, Florida, United States

Orlando Clinical Research Center ( Site 0002)

Orlando, Florida, United States

Countries

United States

References

Nussbaum JC, Hussain A, Min KC, Marbury TC, Lasseter K, Stoch SA, Iwamoto M. Effects of Renal Impairment on the Pharmacokinetics of Gefapixant, a P2X3 Receptor Antagonist. J Clin Pharmacol. 2022 Nov;62(11):1435-1444. doi: 10.1002/jcph.2094. Epub 2022 Jul 7.

Reference Type: RESULT

PMID: 35656754 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

MK-7264-026-003

Identifier Type: OTHER

Identifier Source: secondary_id

7264-026

Identifier Type: -

Identifier Source: org_study_id