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

• Gefapixant (Drug), also known as MK-7264: After an overnight fast participants receive a single oral dose of 50 mg gefapixant, in one 50 mg tablet.

Primary outcomes

• [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) [Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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.
• [Part 2] Geometric Least Squares Mean (GM) AUC0-inf in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis) [Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With Body Surface Area (BSA)-Normalized Estimated Glomerular Filtration Rate (eGFR) (Regression Analysis) [Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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] Estimated AUC0-inf of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis) [Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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 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) [Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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] Mean Area Under the Concentration-Time Curve of From Time Zero to the Last Quantifiable Sample (AUC0-last) of Gefapixant 50 mg [Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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.
• [Part 2] Geometric Least Squares Mean AUC0-last of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis) [Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis) [Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis) [Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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.
• [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) [Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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] Maximum Concentration (Cmax) of Gefapixant 50 mg [Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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.
• [Part 2] Geometric Least Squares Mean Cmax of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis) [Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis) [Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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] Estimated Cmax of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis) [Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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 and 2] Estimated Cmax of Gefapixant 50 mg in Participants With Moderate RI, Severe RI, ESRD Non-HD, or Normal Renal Function (Categorical Analysis) [Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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] Apparent Clearance (CL/F) of Gefapixant 50 mg [Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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.
• [Part 2] Geometric Least Squares Mean CL/F of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis) [Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis) [Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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] Estimated CL/F of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis) [Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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.
• [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) [Parts 1 and 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose]: 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] Renal Clearance (CLr) of Gefapixant 50 mg [Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose]: 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] Estimated CLr of Gefapixant 50 mg in Participants With Moderate RI, Severe RI, or Normal Renal Function (Categorical Analysis) [Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose]: 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] Estimated CLr of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis) [Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose]: 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] Estimated CLr of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis) [Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose]: 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.

Secondary outcomes

• [Parts 1 and 2] Number of Participants Experiencing an Adverse Event (AE) [Parts 1 and 2 - Up to 29 days.]: 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] Number of Participants Discontinuing Study Treatment Due to an AE [Part 1 and 2 - Up to 15 days]: 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.

Sex: All, ages: 18 Years to 80 Years, 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.

Participant flow

Outcome results

• [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) (Primary), Mean, ng*hr/mL: [Part 1] Moderate RI 6450 +/- 1910; [Part 1] Severe RI 9970 +/- 4080; [Part 2, Period 1] ESRD Non-HD 9990 +/- 3610; [Part 2, Period 2] ESRD HD 8590 +/- 4190; [Part 1 and Part 2] Healthy Controls 2280 +/- 1160
• [Part 2] Geometric Least Squares Mean (GM) AUC0-inf in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis) (Primary), Geometric least squares mean, ng*hr/mL: [Part 2, Period 1] ESRD Non-HD 10100 (6300 to 16200); [Part 2, Period 2] ESRD HD 7810 (4740 to 12900)
• [Part 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With Body Surface Area (BSA)-Normalized Estimated Glomerular Filtration Rate (eGFR) (Regression Analysis) (Primary), Mean, ng*hr/mL: [Part 1] Moderate RI 6350 (5210 to 7750); [Part 1] Severe RI 8580 (6710 to 11000); [Part 1] Healthy Controls 2280 (1700 to 3050)
• [Part 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis) (Primary), Mean, ng*hr/mL: [Part 1] Moderate RI 6850 (5580 to 8410); [Part 1] Severe RI 8840 (6900 to 11300); [Part 1] Healthy Controls 2370 (1790 to 3130)
• [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) (Primary), Geometric least squares mean, ng*hr/mL: [Part 1] Moderate RI 6230 (4610 to 8400); [Part 1] Severe RI 9270 (5940 to 14500); [Part 2, Period 1] ESRD Non-HD 9900 (5940 to 16500); [Part 1] Healthy Controls 2090 (1320 to 3310)
• [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 (Primary), Mean, ng*hr/mL: [Part 1] Moderate RI 5930 +/- 1950; [Part 1] Severe RI 7630 +/- 3080; [Part 2, Period 1] ESRD Non-HD 7790 +/- 2740; [Part 2, Period 2] ESRD HD 6460 +/- 2640; [Part 1] Healthy Controls 2000 +/- 1230
• [Part 2] Geometric Least Squares Mean AUC0-last of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis) (Primary), Geometric least squares mean, ng*hr/mL: [Part 2, Period 1] ESRD Non-HD 7870 (5080 to 12200); [Part 2, Period 2] ESRD HD 6030 (3930 to 9260)
• [Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis) (Primary), Mean, ng*hr/mL: [Part 1] Moderate RI 5310 (4280 to 6590); [Part 1] Severe RI 7130 (5470 to 9300); [Part 1] Healthy Controls 1940 (1410 to 2660)
• [Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis) (Primary), Mean, ng*hr/mL: [Part 1] Moderate RI 5740 (4620 to 7120); [Part 1] Severe RI 7380 (5690 to 9580); [Part 1] Healthy Controls 2000 (1490 to 2680)
• [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) (Primary), Geometric least squares mean, ng*hr/mL: [Part 1] Moderate RI 5670 (4050 to 7940); [Part 1] Severe RI 7170 (4800 to 10700); [Part 2, Period 1] ESRD Non-HD 7770 (4840 to 12500); [Part 1] Healthy Controls 1760 (995 to 3100)
• [Parts 1 and 2] Maximum Concentration (Cmax) of Gefapixant 50 mg (Primary), Mean, ng/mL: [Part 1] Moderate RI 338 +/- 127; [Part 1] Severe RI 311 +/- 137; [Part 2, Period 1] ESRD Non-HD 281 +/- 92.5; [Part 2, Period 2] ESRD HD 228 +/- 87.1; [Part 1] Healthy Controls 173 +/- 95.7
• [Part 2] Geometric Least Squares Mean Cmax of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis) (Primary), Geometric least squares mean, ng/mL: [Part 2, Period 1] ESRD Non-HD 292 (194 to 439); [Part 2, Period 2] ESRD HD 214 (142 to 322)
• [Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis) (Primary), Mean, ng/mL: [Part 1] Moderate RI 272 (211 to 351); [Part 1] Severe RI 318 (233 to 435); [Part 1] Healthy Controls 160 (110 to 232)
• [Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis) (Primary), Mean, ng/mL: [Part 1] Moderate RI 286 (222 to 369); [Part 1] Severe RI 329 (242 to 447); [Part 1] Healthy Controls 160 (113 to 226)
• [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) (Primary), Geometric least squares mean, ng/mL: [Part 1] Moderate RI 316 (201 to 496); [Part 1] Severe RI 286 (178 to 458); [Part 2, Period 1] ESRD Non-HD 287 (187 to 441); [Part 1] Healthy Controls 151 (82.8 to 277)
• [Parts 1 and 2] Apparent Clearance (CL/F) of Gefapixant 50 mg (Primary), Mean, L/hr: [Part 1] Moderate RI 8.30 +/- 2.25; [Part 1] Severe RI 5.81 +/- 2.47; [Part 2, Period 1] ESRD Non-HD 5.67 +/- 2.28; [Part 2, Period 2] ESRD HD 7.00 +/- 3.09; [Part 1] Healthy Controls 25.7 +/- 9.42
• [Part 2] Geometric Least Squares Mean CL/F of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis) (Primary), Geometric least squares mean, L/hr: [Part 2, Period 1] ESRD Non-HD 4.95 (3.08 to 7.94); [Part 2, Period 2] ESRD HD 6.40 (3.89 to 10.6)
• [Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis) (Primary), Mean, L/hr: [Part 1] Moderate RI 7.87 (6.45 to 9.60); [Part 1] Severe RI 5.83 (4.56 to 7.45); [Part 1] Healthy Controls 21.9 (16.4 to 29.4)
• [Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis) (Primary), Mean, L/hr: [Part 1] Moderate RI 7.30 (5.95 to 8.96); [Part 1] Severe RI 5.66 (4.42 to 7.24); [Part 1] Healthy Controls 21.1 (16.0 to 27.9)
• [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) (Primary), Geometric least squares mean, L/hr: [Part 1] Moderate RI 8.03 (5.95 to 10.8); [Part 1] Severe RI 5.40 (3.46 to 8.41); [Part 2, Period 1] ESRD Non-HD 5.05 (3.03 to 8.42); [Part 1] Healthy Controls 23.9 (15.1 to 37.9)
• 6 more outcome measures not shown.

Adverse events

Time frame: Up to 29 days

Other adverse events by term

• Results publication: 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. PMID 35656754

• Study Protocol (PDF, 2017-06-09)
• Statistical Analysis Plan (PDF, 2017-06-09)

• Medical Director, Study director, Merck Sharp & Dohme LLC