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Phase 1 N=24 Treatment

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

Renal Insufficiency

Enrolled (actual)
24
Serious AEs
0.0%
Results posted
Aug 2019
Primary outcome: Primary: [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) — 6450; 9970; 9990; 8590 ng*hr/mL

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
Gefapixant (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Merck Sharp & Dohme LLC
Primary completion
Sep 2017

Outcome Measures

OutcomeResultp-value
PRIMARY
[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)
6450; 9970; 9990; 8590; 2280
PRIMARY
[Part 2] Geometric Least Squares Mean (GM) AUC0-inf in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)
10100; 7810
PRIMARY
[Part 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With Body Surface Area (BSA)-Normalized Estimated Glomerular Filtration Rate (eGFR) (Regression Analysis)
6350; 8580; 2280
PRIMARY
[Part 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
6850; 8840; 2370
PRIMARY
[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)
6230; 9270; 9900; 2090
PRIMARY
[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
5930; 7630; 7790; 6460; 2000
PRIMARY
[Part 2] Geometric Least Squares Mean AUC0-last of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)
7870; 6030
PRIMARY
[Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)
5310; 7130; 1940
PRIMARY
[Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
5740; 7380; 2000
PRIMARY
[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)
5670; 7170; 7770; 1760
PRIMARY
[Parts 1 and 2] Maximum Concentration (Cmax) of Gefapixant 50 mg
338; 311; 281; 228; 173
PRIMARY
[Part 2] Geometric Least Squares Mean Cmax of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)
292; 214
PRIMARY
[Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)
272; 318; 160
PRIMARY
[Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
286; 329; 160
PRIMARY
[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)
316; 286; 287; 151
PRIMARY
[Parts 1 and 2] Apparent Clearance (CL/F) of Gefapixant 50 mg
8.30; 5.81; 5.67; 7.00; 25.7
PRIMARY
[Part 2] Geometric Least Squares Mean CL/F of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)
4.95; 6.40
PRIMARY
[Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)
7.87; 5.83; 21.9
PRIMARY
[Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
7.30; 5.66; 21.1
PRIMARY
[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)
8.03; 5.40; 5.05; 23.9
PRIMARY
[Parts 1 and 2] Renal Clearance (CLr) of Gefapixant 50 mg
2.10; 0.755; 6.72
PRIMARY
[Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With Moderate RI, Severe RI, or Normal Renal Function (Categorical Analysis)
2.05; 0.680; 6.61
PRIMARY
[Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)
1.49; 0.997; 5.95
PRIMARY
[Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)
1.36; 0.975; 5.53
SECONDARY
[Parts 1 and 2] Number of Participants Experiencing an Adverse Event (AE)
0; 2; 0; 1
SECONDARY
[Parts 1 and 2] Number of Participants Discontinuing Study Treatment Due to an AE
0; 0; 0; 0

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.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03108924). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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