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

An Open-Label, Single-Dose Study to Investigate the Influence of Renal Insufficiency on the Pharmacokinetics of MK-7264

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.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency
• Intervention / Treatment: Drug: Gefapixant

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Hialeah, Florida, United States, 33014
      • Clinical Pharmacology of Miami ( Site 0001)
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center ( Site 0002)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate RI; Participants with moderate renal insufficiency (RI) are treated with a single 50 mg dose of gefapixant	Drug: Gefapixant; After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.; Other Names: MK-7264
Experimental: Severe RI; Participants with severe RI are treated with a single 50 mg dose of gefapixant	Drug: Gefapixant; After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.; Other Names: MK-7264
Other: Healthy Matched Controls; Healthy, participants matched for age and body weight are treated with a single 50 mg dose of gefapixant	Drug: Gefapixant; After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.; Other Names: MK-7264
Experimental: 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.	Drug: Gefapixant; After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.; Other Names: MK-7264

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[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)	The mean area under the concentration-time curve from time 0 to infinity (AUC0-inf) of plasma gefapixant was assessed. In Part 1, participants with Moderate RI, Severe RI, or normal renal function (i. e., Healthy Controls) received a single oral dose of gefapixant 50 mg at Hour 0 on Day 1. In Part 2, Period 1, ESRD participants received a single oral dose of gefapixant 50 mg at Hour 0 on Day 1, immediately following the scheduled HD. In Part 2, Period 2, participants received a single oral dose of gefapixant 50 mg at Hour 0 on Day 1, approximately 2 hours prior to initiation of HD. Non-model based summary statistics were provided for the number of participants with non-missing data, as well as mean and standard deviation values. Serial blood samples for the determination of plasma gefapixant concentrations were collected at predose and at selected time points over 72 hours postdose.	Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 2] Geometric Least Squares Mean (GM) AUC0-inf in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)	To evaluate the extent of gefapixant removal by hemodialysis, individual values of AUC0-inf, were natural log (ln)-transformed and analyzed using a linear mixed-effects model with population (ESRD Non-HD, ESRD HD) as a fixed effect. An unstructured covariance matrix was used to allow for unequal variances and to model the correlation between the 2 measurements within each participant. A two-sided 90% confidence interval (CI) for the true difference in means was calculated for AUC0-inf. These confidence limits were exponentiated to obtain the 90% CI for the geometric least squares mean ratio (GMR) (ESRD HD/ESRD Non-HD) for AUC0-inf.	Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With Body Surface Area (BSA)-Normalized Estimated Glomerular Filtration Rate (eGFR) (Regression Analysis)	AUC0-inf values of plasma gefapixant based on BSA-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of AUC0-inf were natural log-transformed and evaluated with a linear fixed-effects model containing BSA-normalized eGFR as a continuous variable. The back transformed mean AUC0-inf and corresponding 95% CI were predicted at the midpoint of the BSA enormalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their normalized eGFR estimates were predicted at midpoint 75 mL/min.	Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	AUC0-inf values of plasma gefapixant based on BSA non-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of AUC0-inf were natural log-transformed and evaluated with a linear fixed-effects model containing BSA non-normalized eGFR as a continuous variable. The back transformed mean AUC0-inf and corresponding 95% CI were predicted at the midpoint of the BSA non-normalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their BSA non-normalized eGFR estimates were predicted at midpoint 75 mL/min.	Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[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)	Geometric mean and 95%CI for AUC0-inf were estimated in participants with moderate RI, severe RI, ESRD requiring but not receiving HD, and normal renal function (i. e., Healthy Controls). Individual values of AUC0-inf, were ln-transformed and evaluated with a linear fixed-effects heterogeneous variance model containing a categorical effect for population (ESRD Non-HD, severe RI, moderate RI, and healthy matched control, based on BSA normalized eGFR). To compare subjects with RI in each of the renal categories to subjects with normal renal function, a two-sided 90% CI for the true difference in means (renal impairment - normal renal function) was calculated for AUC0-inf, using the mean square error from the model and referencing a t-distribution. For each of the RI populations, these confidence limits were exponentiated to obtain the 90% CI for the GMR (renal impairment/normal renal function).	Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[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	The mean area under the concentration-time curve from time 0 to the last quantifiable sample (AUC0-last), above the lower limit of quantitation (LLOQ), of plasma gefapixant in participants with moderate RI, severe RI, ESRD, or normal renal function (i. e., Healthy Controls) was assessed. Non-model based summary statistics were provided for the number of participants with non-missing data, as well as mean and standard deviation values.	Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 2] Geometric Least Squares Mean AUC0-last of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)	To evaluate the extent of gefapixant removal by hemodialysis, individual values of AUC0-last, were ln-transformed and analyzed using a linear mixed-effects model with population (ESRD Non-HD, ESRD HD) as a fixed effect. An unstructured covariance matrix was used to allow for unequal variances and to model the correlation between the 2 measurements within each participant. A two-sided 90% CI for the true difference in means was calculated for AUC0-last. These confidence limits were exponentiated to obtain the 90% CI for the geometric least squares mean ratio (GMR) (ESRD HD/ESRD Non-HD) for AUC0-last.	Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)	AUC0-last values of plasma gefapixant based on BSA-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of AUC0last were natural log-transformed and evaluated with a linear fixed-effects model containing BSA-normalized eGFR as a continuous variable. The mean AUC0-ilast and corresponding 95% CI were back-transformed and predicted at the midpoint of th BSA enormalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their normalized eGFR estimates were predicted at midpoint 75 mL/min.	Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	AUC0-last values of plasma gefapixant based on BSA non-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of AUC0-last were natural log-transformed and evaluated with a linear fixed-effects model containing BSA non-normalized eGFR as a continuous variable. The back transformed mean AUC0-last and corresponding 95% CI were predicted at the midpoint of the BSA non-normalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their BSA non-normalized eGFR estimates were predicted at midpoint 75 mL/min.	Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[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)	Geometric mean and 95%CI for AUC0-last were estimated in participants with moderate RI, severe RI, ESRD requiring but not receiving HD, and normal renal function (i. e., Healthy Controls). Individual values of AUC0-last, were ln-transformed and evaluated with a linear fixed-effects heterogeneous variance model containing a categorical effect for population (ESRD Non-HD, severe RI, moderate RI, and healthy matched control, based on BSA normalized eGFR). To compare subjects with RI in each of the renal categories to subjects with normal renal function, a two-sided 90% CI for the true difference in means (renal impairment - normal renal function) was calculated for AUC0-last, using the mean square error from the model and referencing a t-distribution. For each of the RI populations, these confidence limits were exponentiated to obtain the 90% CI for the GMR (renal impairment/normal renal function).	Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Parts 1 and 2] Maximum Concentration (Cmax) of Gefapixant 50 mg	The maximum concentration (Cmax) of plasma gefapixant in participants with moderate RI, severe RI, ESRD Non-HD, ESRD HD, or normal renal function (i. e., Healthy Controls) following administration of gefapixant 50 mg was assessed. Non-model based summary statistics were provided for the number of participants with non-missing data, as well as mean and standard deviation values. Serial blood samples for the determination of plasma gefapixant concentrations were collected at predose and at selected time points over 72 hours postdose.	Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 2] Geometric Least Squares Mean Cmax of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)	To evaluate the extent of gefapixant removal by hemodialysis, individual values of Cmax, were ln transformed and analyzed using a linear mixed-effects model with population (ESRD Non-HD, ESRD HD) as a fixed effect. An unstructured covariance matrix was used to allow for unequal variances and to model the correlation between the 2 measurements within each participant. A two-sided 90% CI for the true difference in means was calculated for Cmax. These confidence limits were exponentiated to obtain the 90% CI for the geometric least squares mean ratio (GMR) (ESRD HD/ESRD Non-HD) for Cmax.	Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)	Cmax values of plasma gefapixant based on BSA-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of Cmax were natural log-transformed and evaluated with a linear fixed-effects model containing BSA-normalized eGFR as a continuous variable. The back transformed mean Cmax and corresponding 95% CI were predicted at the midpoint of the BSA enormalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their normalized eGFR estimates were predicted at midpoint 75 mL/min. Serial blood samples for the determination of plasma gefapixant concentrations were collected at predose and at selected time points over 72 hours postdose.	Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	Cmax values of plasma gefapixant based on BSA non-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of Cmax were natural log-transformed and evaluated with a linear fixed-effects model containing BSA non-normalized eGFR as a continuous variable. The back transformed mean Cmax and corresponding 95% CI were predicted at the midpoint of the BSA non-normalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their BSA non-normalized eGFR estimates were predicted at midpoint 75 mL/min. Serial blood samples for the determination of plasma gefapixant concentrations were collected at predose and at selected time points over 72 hours postdose.	Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[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)	Geometric mean and 95%CI for Cmax were estimated in participants with moderate RI, severe RI, ESRD requiring but not receiving HD, and normal renal function (i. e., Healthy Controls). Individual values of Cmax, were ln-transformed and evaluated with a linear fixed-effects heterogeneous variance model containing a categorical effect for population (ESRD Non-HD, severe RI, moderate RI, and healthy matched control, based on BSA normalized eGFR). To compare subjects with RI in each of the renal categories to subjects with normal renal function, a two-sided 90% CI for the true difference in means (renal impairment - normal renal function) was calculated for Cmax, using the mean square error from the model and referencing a t-distribution. For each of the RI populations, these confidence limits were exponentiated to obtain the 90% CI for the GMR (renal impairment/normal renal function).	Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Parts 1 and 2] Apparent Clearance (CL/F) of Gefapixant 50 mg	The apparent clearance (CL/F) of plasma gefapixant after oral administration of gefapixant 50 mg in participants with moderate RI, severe RI, ESRD requiring HD, or normal renal function (i. e., Healthy Controls) was assessed. Non-model based summary statistics were provided for the number of participants with non-missing data, as well as mean and standard deviation values. Serial blood samples for the determination of plasma gefapixant concentrations were collected at predose and at selected time points over 72 hours postdose.	Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 2] Geometric Least Squares Mean CL/F of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)	To evaluate the extent of gefapixant removal by hemodialysis, individual values of CL/F, were ln-transformed and analyzed using a linear mixed-effects model with population (ESRD Non-HD, ESRD HD) as a fixed effect. An unstructured covariance matrix was used to allow for unequal variances and to model the correlation between the 2 measurements within each participant. A two-sided 90% CI for the true difference in means was calculated for CL/F. These confidence limits were exponentiated to obtain the 90% CI for the geometric least squares mean ratio (GMR) (ESRD HD/ESRD Non-HD) for CL/F.	Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)	CL/F values of plasma gefapixant based on BSA-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of CL/F were natural log-transformed and evaluated with a linear fixed-effects model containing BSA-normalized eGFR as a continuous variable. The back transformed mean CL/F and corresponding 95% CI were predicted at the midpoint of the BSA enormalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their normalized eGFR estimates were predicted at midpoint 75 mL/min.	Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	CL/F values of plasma gefapixant based on BSA non-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of CL/F were natural log-transformed and evaluated with a linear fixed-effects model containing BSA non-normalized eGFR as a continuous variable. The back transformed mean CL/F and corresponding 95% CI were predicted at the midpoint of the BSA non-normalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their BSA non-normalized eGFR estimates were predicted at midpoint 75 mL/min.	Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[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)	Geometric mean and 95% CI for CL/F were estimated in participants with moderate RI, severe RI, ESRD requiring but not receiving HD, and normal renal function (i. e., Healthy Controls). Individual values of CL/F, were ln-transformed and evaluated with a linear fixed-effects heterogeneous variance model containing a categorical effect for population (ESRD Non-HD, severe RI, moderate RI, and healthy matched control, based on BSA normalized eGFR). To compare subjects with RI in each of the renal categories to subjects with normal renal function, a two-sided 90% CI for the true difference in means (renal impairment - normal renal function) was calculated for CL/F, using the mean square error from the model and referencing a t-distribution. For each of the RI populations, these confidence limits were exponentiated to obtain the 90% CI for the GMR (renal impairment/normal renal function).	Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose
[Parts 1 and 2] Renal Clearance (CLr) of Gefapixant 50 mg	The renal clearance (CLr) in participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) was assessed. Non-model base summary statistics were provided. Renal clearance could not be assessed for participants with ESRD. Urine specimens were obtained by spot collection predose and at multiple timepoints postdose.	Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose
[Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With Moderate RI, Severe RI, or Normal Renal Function (Categorical Analysis)	Geometric mean and 95% CI for CLr were estimated in participants with moderate RI, severe RI, and normal renal function (i. e., Healthy Controls). Individual values of CLr, were ln-transformed and evaluated with a linear fixed-effects heterogeneous variance model containing a categorical effect for population (severe RI, moderate RI, and healthy matched control, based on BSA normalized eGFR). To compare subjects with RI in each of the renal categories to subjects with normal renal function, a two-sided 90% CI for the true difference in means (renal impairment - normal renal function) was calculated for CLr, using the mean square error from the model and referencing a t-distribution. For each of the RI populations, these confidence limits were exponentiated to obtain the 90% CI for the GMR (renal impairment/normal renal function).	Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose
[Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)	CLr values of plasma gefapixant based on BSA-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of CLr were natural log-transformed and evaluated with a linear fixed-effects model containing BSA-normalized eGFR as a continuous variable. The back transformed mean CLr and corresponding 95% CI were predicted at the midpoint of the BSA-normalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their normalized eGFR estimates were predicted at midpoint 75 mL/min.	Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose
[Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	CLr values of plasma gefapixant based on BSA non-normalized eGFR for participants with moderate RI, severe RI, or normal renal function (i. e., Healthy Controls) were estimated using regression analysis. Individual values of CLr were natural log-transformed and evaluated with a linear fixed-effects model containing BSA non-normalized eGFR as a continuous variable. The back transformed mean AUC0-inf and corresponding 95% CI were predicted at the midpoint of the BSA non-normalized eGFR range for each group (45 mL/min, 22.5 mL/min, and 139 mL/min for moderate RI, severe RI, and healthy controls, respectively). Although no participants with mild RI were included in this study, their BSA non-normalized eGFR estimates were predicted at midpoint 75 mL/min.	Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[Parts 1 and 2] Number of Participants Experiencing an Adverse Event (AE)	The number of participants who experienced at least one adverse event (AE) was assessed. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.	Parts 1 and 2 - Up to 29 days.
[Parts 1 and 2] Number of Participants Discontinuing Study Treatment Due to an AE	The number of participants who discontinued study treatment due to an AE was assessed. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.	Part 1 and 2 - Up to 15 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2017
• Primary Completion (Actual): September 3, 2017
• Study Completion (Actual): September 13, 2017

Study Registration Dates

• First Submitted: April 6, 2017
• First Submitted That Met QC Criteria: April 6, 2017
• First Posted (Actual): April 11, 2017

Study Record Updates

• Last Update Posted (Actual): July 27, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: 7264-026; MK-7264-026-003 (Other Identifier: Merck Protocol Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No