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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Renal Insufficiency

Treatments: Drug: Gefapixant

Study type: Interventional

Funder types: Industry

Identifiers

NCT03108924

MK-7264-026-003 (Other Identifier)

7264-026

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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24 participants in 4 patient groups

Moderate RI

Experimental group

Description:

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

Treatment:

Drug: Gefapixant

Severe RI

Experimental group

Description:

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

Treatment:

Drug: Gefapixant

Healthy Matched Controls

Other group

Description:

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

Treatment:

Drug: Gefapixant

ESRD Requiring HD

Experimental group

Description:

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.

Treatment:

Drug: Gefapixant