Clinical trial NCT03108924: The Pharmacokinetics of Gefapixant (MK-7264) in Participants With Renal Insufficiency (MK-7264-026)
Official title: An Open-Label, Single-Dose Study to Investigate the Influence of Renal Insufficiency on the Pharmacokinetics of MK-7264
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Insufficiency
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-04-11
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: [Parts 1 and 2] Mean Area Under the Concentration-Time Curve From Time Zero Up to Infinity (AUC0-inf) of Gefapixant 50 mg (Categorical Analysis)
timeFrame: Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 2] Geometric Least Squares Mean (GM) AUC0-inf in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)
timeFrame: Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With Body Surface Area (BSA)-Normalized Estimated Glomerular Filtration Rate (eGFR) (Regression Analysis)
timeFrame: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
timeFrame: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1 and 2] Estimated AUC0-inf of Gefapixant 50 mg in Participants With Moderate RI, Severe RI, ESRD Non-HD, or Normal Renal Function (Categorical Analysis)
timeFrame: Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Parts 1 and 2] Mean Area Under the Concentration-Time Curve of From Time Zero to the Last Quantifiable Sample (AUC0-last) of Gefapixant 50 mg
timeFrame: Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 2] Geometric Least Squares Mean AUC0-last of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)
timeFrame: Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)
timeFrame: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
timeFrame: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Parts 1 and 2] Estimated AUC0-last of Gefapixant 50 mg in Participants With Moderate RI, Severe RI, ESRD Non-HD, or Normal Renal Function (Categorical Analysis)
timeFrame: Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Parts 1 and 2] Maximum Concentration (Cmax) of Gefapixant 50 mg
timeFrame: Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 2] Geometric Least Squares Mean Cmax of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)
timeFrame: Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)
timeFrame: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
timeFrame: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1 and 2] Estimated Cmax of Gefapixant 50 mg in Participants With Moderate RI, Severe RI, ESRD Non-HD, or Normal Renal Function (Categorical Analysis)
timeFrame: Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Parts 1 and 2] Apparent Clearance (CL/F) of Gefapixant 50 mg
timeFrame: Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 2] Geometric Least Squares Mean CL/F of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)
timeFrame: Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)
timeFrame: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
timeFrame: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Parts 1 and 2] Estimated CL/F of Gefapixant 50 mg in Participants With Moderate RI, Severe RI, ESRD Non-HD, or Normal Renal Function (Categorical Analysis)
timeFrame: Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
measure: [Parts 1 and 2] Renal Clearance (CLr) of Gefapixant 50 mg
timeFrame: Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose
measure: [Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With Moderate RI, Severe RI, or Normal Renal Function (Categorical Analysis)
timeFrame: Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose
measure: [Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)
timeFrame: Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose
measure: [Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
timeFrame: Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose
Secondary outcomes:
measure: [Parts 1 and 2] Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Parts 1 and 2 - Up to 29 days.
measure: [Parts 1 and 2] Number of Participants Discontinuing Study Treatment Due to an AE
timeFrame: Part 1 and 2 - Up to 15 days
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: Clinical Pharmacology of Miami ( Site 0001)
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center ( Site 0002)
state: Florida
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.