Trial Outcomes & Findings for The Pharmacokinetics of Gefapixant (MK-7264) in Participants With Renal Insufficiency (MK-7264-026) (NCT NCT03108924)

NCT ID: NCT03108924

Last Updated: 2022-07-27

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 24 participants
• Primary outcome 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
• Results posted on: 2022-07-27

Participant Flow

This was an open-label, 2-part, single dose study. In Part 1, MK-7264 was evaluated in participants with moderate and severe renal impairment (RI) compared to healthy matched control participants. In Part 2, MK-7264 was evaluated in 2 periods in participants with end stage renal disease (ESRD) requiring hemodialysis (HD).

Participant milestones

Measure	[Part 1] Moderate RI Participants with moderate renal impairment (RI) received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2] ESRD Participants with ESRD requiring HD received a single oral dose of gefapixant 50 mg immediately after HD in Period 1, followed by a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between the Periods 1 and 2 MK-7264 dose administrations there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
Overall Study STARTED	6	6	6	6
Overall Study COMPLETED	6	6	6	6
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2] ESRD n=6 Participants Participants with ESRD requiring HD received a single oral dose of gefapixant 50 mg immediately after HD in Period 1, followed by a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between the Periods 1 and 2 MK-7264 dose administrations there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls n=6 Participants Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).	Total n=24 Participants Total of all reporting groups
Age, Continuous	66.3 years STANDARD_DEVIATION 10.76 • n=5 Participants	64.3 years STANDARD_DEVIATION 5.75 • n=7 Participants	52.7 years STANDARD_DEVIATION 7.12 • n=5 Participants	65.8 years STANDARD_DEVIATION 5.00 • n=4 Participants	62.3 years STANDARD_DEVIATION 9.0 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	20 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	12 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	4 Participants n=4 Participants	12 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	9 Participants n=21 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	15 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

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

Population: All participants in Parts 1 and 2 who were compliant with the study procedure and had available data were included. The ESRD Non-HD and ESRD HD arms are a split of the original ESRD arm. The same 6 participants are in both Periods 1 and 2.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls n=6 Participants Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[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 ng*hr/mL Standard Deviation 1910	9970 ng*hr/mL Standard Deviation 4080	9990 ng*hr/mL Standard Deviation 3610	8590 ng*hr/mL Standard Deviation 4190	2280 ng*hr/mL Standard Deviation 1160

PRIMARY outcome

Timeframe: Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 2 who were compliant with the study procedure and had available data were included. A single participant with 6 missing plasma samples in Part 2, Period 1 was excluded from the ESRD Non-HD group. The ESRD Non-HD and ESRD HD arms are a split of the original ESRD arm. The same 6 participants were in Periods 1 and 2.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=5 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 2] Geometric Least Squares Mean (GM) AUC0-inf in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)	10100 ng*hr/mL Interval 6300.0 to 16200.0	7810 ng*hr/mL Interval 4740.0 to 12900.0	—	—	—

PRIMARY outcome

Timeframe: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 1 who were compliant with the study procedure and had available data were included.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[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 ng*hr/mL Interval 5210.0 to 7750.0	8580 ng*hr/mL Interval 6710.0 to 11000.0	2280 ng*hr/mL Interval 1700.0 to 3050.0	—	—

PRIMARY outcome

Timeframe: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 1 who were compliant with the study procedure and had available data were included. For non-normalized eGFR estimates, participants originally assigned to the severe RI group were reassigned: 1 participant reassigned to the mild RI group (excluded from analysis), and 1 participant reassigned to the moderate RI group.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=7 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=4 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 1] Estimated AUC0-inf of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	6850 ng*hr/mL Interval 5580.0 to 8410.0	8840 ng*hr/mL Interval 6900.0 to 11300.0	2370 ng*hr/mL Interval 1790.0 to 3130.0	—	—

PRIMARY outcome

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

Population: All participants in Parts 1 and 2 were compliant with the study procedure and had available data were included. A single participant with 6 missing plasma samples in Part 2, Period 1 was excluded from the ESRD Non-HD group. The same 6 participants were in Periods 1 and 2.

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).

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=5 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[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 ng*hr/mL Interval 4610.0 to 8400.0	9270 ng*hr/mL Interval 5940.0 to 14500.0	9900 ng*hr/mL Interval 5940.0 to 16500.0	2090 ng*hr/mL Interval 1320.0 to 3310.0	—

PRIMARY outcome

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

Population: All participants in Parts 1 and 2 who were compliant with the study procedure and had available data were included. The ESRD Non-HD and ESRD HD arms are a split of the original ESRD arm. The same 6 participants are in both Periods 1 and 2.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls n=6 Participants Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[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 ng*hr/mL Standard Deviation 1950	7630 ng*hr/mL Standard Deviation 3080	7790 ng*hr/mL Standard Deviation 2740	6460 ng*hr/mL Standard Deviation 2640	2000 ng*hr/mL Standard Deviation 1230

PRIMARY outcome

Timeframe: Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 2 who complied with the study procedure and had available data were included. A single participant with 6 missing plasma samples in Part 2, Period 1 was excluded from the ESRD Non-HD group. The ESRD Non-HD and ESRD HD arms were split from the original ESRD arm. The same 6 participants were in Periods 1 and 2.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=5 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 2] Geometric Least Squares Mean AUC0-last of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)	7870 ng*hr/mL Interval 5080.0 to 12200.0	6030 ng*hr/mL Interval 3930.0 to 9260.0	—	—	—

PRIMARY outcome

Timeframe: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 1 who were compliant with the study procedure and had available data were included.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)	5310 ng*hr/mL Interval 4280.0 to 6590.0	7130 ng*hr/mL Interval 5470.0 to 9300.0	1940 ng*hr/mL Interval 1410.0 to 2660.0	—	—

PRIMARY outcome

Timeframe: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 1 who were compliant with the study procedure and had available data were included. For non-normalized eGFR estimates, participants originally assigned to the severe RI group were reassigned: 1 participant reassigned to the mild RI group (excluded from analysis), and 1 participant reassigned to the moderate RI group.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=7 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=4 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 1] Estimated AUC0-last of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	5740 ng*hr/mL Interval 4620.0 to 7120.0	7380 ng*hr/mL Interval 5690.0 to 9580.0	2000 ng*hr/mL Interval 1490.0 to 2680.0	—	—

PRIMARY outcome

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

Population: All participants in Parts 1 and 2 who were compliant with the study procedure and had available data were included. A single participant was excluded from the ESRD Non-HD group since this participant had 6 missing peripheral plasma samples in Part 2, Period 1.

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).

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=5 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[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 ng*hr/mL Interval 4050.0 to 7940.0	7170 ng*hr/mL Interval 4800.0 to 10700.0	7770 ng*hr/mL Interval 4840.0 to 12500.0	1760 ng*hr/mL Interval 995.0 to 3100.0	—

PRIMARY outcome

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

Population: All participants in Parts 1 and 2 who were compliant with the study procedure and had available data were included in the primary analysis dataset at the end of the study. The ESRD Non-HD and ESRD HD arms are a split of the original ESRD arm. The same 6 participants were in both Periods 1 and 2.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls n=6 Participants Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Parts 1 and 2] Maximum Concentration (Cmax) of Gefapixant 50 mg	338 ng/mL Standard Deviation 127	311 ng/mL Standard Deviation 137	281 ng/mL Standard Deviation 92.5	228 ng/mL Standard Deviation 87.1	173 ng/mL Standard Deviation 95.7

PRIMARY outcome

Timeframe: Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 2 who complied with the study procedure and had available data were included. A single participant with 6 missing plasma samples in Part 2, Period 1 was excluded from the ESRD Non-HD group. The ESRD Non-HD and ESRD HD arms were split from the original ESRD arm. The same 6 participants were in Periods 1 and 2.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=5 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 2] Geometric Least Squares Mean Cmax of Gefapixant 50 mg in ESRD HD Participants vs. ESRD Non-HD Participants (Categorical Analysis)	292 ng/mL Interval 194.0 to 439.0	214 ng/mL Interval 142.0 to 322.0	—	—	—

PRIMARY outcome

Timeframe: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 1 who were compliant with the study procedure and had available data were included.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)	272 ng/mL Interval 211.0 to 351.0	318 ng/mL Interval 233.0 to 435.0	160 ng/mL Interval 110.0 to 232.0	—	—

PRIMARY outcome

Timeframe: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 1 who were compliant with the study procedure and had available data were included. For non-normalized eGFR estimates, participants originally assigned to the severe RI group were reassigned: 1 participant reassigned to the mild RI group (excluded from analysis), and 1 participant reassigned to the moderate RI group.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=7 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=4 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 1] Estimated Cmax of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	286 ng/mL Interval 222.0 to 369.0	329 ng/mL Interval 242.0 to 447.0	160 ng/mL Interval 113.0 to 226.0	—	—

PRIMARY outcome

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

Population: All Parts 1 and 2 participants who were compliant with the study procedure and had available data were included. A single participant was excluded from the ESRD Non-HD group since this participant had 6 missing peripheral plasma samples in Part 2, Period 1.

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).

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=5 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[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 ng/mL Interval 201.0 to 496.0	286 ng/mL Interval 178.0 to 458.0	287 ng/mL Interval 187.0 to 441.0	151 ng/mL Interval 82.8 to 277.0	—

PRIMARY outcome

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

Population: All participants in Parts 1 and 2 who were compliant with the study procedure and had available data were included. The ESRD Non-HD and ESRD HD arms were split from the original ESRD arm. The same 6 participants were in Periods 1 and 2.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls n=6 Participants Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Parts 1 and 2] Apparent Clearance (CL/F) of Gefapixant 50 mg	8.30 L/hr Standard Deviation 2.25	5.81 L/hr Standard Deviation 2.47	5.67 L/hr Standard Deviation 2.28	7.00 L/hr Standard Deviation 3.09	25.7 L/hr Standard Deviation 9.42

PRIMARY outcome

Timeframe: Part 2 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 2 who were compliant with the study procedure and had available data were included. A single participant with 6 missing plasma samples in Part 2, Period 1 was excluded from the ESRD Non-HD group. The ESRD Non-HD and ESRD HD arms are a split of the original ESRD arm. The same 6 participants were in Periods 1 and 2.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=5 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[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 L/hr Interval 3.08 to 7.94	6.40 L/hr Interval 3.89 to 10.6	—	—	—

PRIMARY outcome

Timeframe: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 1 who were compliant with the study procedure and had available data were included.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)	7.87 L/hr Interval 6.45 to 9.6	5.83 L/hr Interval 4.56 to 7.45	21.9 L/hr Interval 16.4 to 29.4	—	—

PRIMARY outcome

Timeframe: Part 1 - Predose, 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, and 72 hours postdose

Population: All participants in Part 1 who were compliant with the study procedure and had available data were included. For non-normalized eGFR estimates, participants originally assigned to the severe RI group were reassigned: 1 participant reassigned to the mild RI group (excluded from analysis), and 1 participant reassigned to the moderate RI group.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=7 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=4 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Part 1] Estimated CL/F of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	7.30 L/hr Interval 5.95 to 8.96	5.66 L/hr Interval 4.42 to 7.24	21.1 L/hr Interval 16.0 to 27.9	—	—

PRIMARY outcome

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

Population: All participants in Parts 1 and 2 who were compliant with the study procedure and had available data were included. A single participant with 6 missing plasma samples in Part 2, Period 1 was excluded from the ESRD Non-HD group.

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).

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=5 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[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 L/hr Interval 5.95 to 10.8	5.40 L/hr Interval 3.46 to 8.41	5.05 L/hr Interval 3.03 to 8.42	23.9 L/hr Interval 15.1 to 37.9	—

PRIMARY outcome

Timeframe: Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose

Population: All participants who were compliant with the study procedure and had available data were included. Renal clearance could not be assessed for participants with ESRD.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Parts 1 and 2] Renal Clearance (CLr) of Gefapixant 50 mg	2.10 L/hr Standard Deviation 0.522	0.755 L/hr Standard Deviation 0.387	6.72 L/hr Standard Deviation 1.28	—	—

PRIMARY outcome

Timeframe: Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose

Population: All participants in Parts 1 and 2 who were compliant with the study procedure and had available data were included. Renal clearance could not be assessed for participants with ESRD.

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).

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[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 L/hr Interval 1.59 to 2.65	0.680 L/hr Interval 0.403 to 1.15	6.61 L/hr Interval 5.34 to 8.17	—	—

PRIMARY outcome

Timeframe: Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose

Population: All participants in Parts 1 and 2 who were compliant with the study procedure and had available data were included. This population was used for regression analysis of the BSA-normalized CLr of gefapixant 50 mg. Renal clearance could not be assessed for participants with ESRD.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With BSA-Normalized eGFR (Regression Analysis)	1.49 L/hr Interval 1.13 to 1.97	0.997 L/hr Interval 0.711 to 1.4	5.95 L/hr Interval 3.97 to 8.91	—	—

PRIMARY outcome

Timeframe: Parts 1 and 2 - Predose and at 0-12 hrs, 12-24 hrs, and 24-48 hrs post dose

Population: All participants in Parts 1 and 2 who were compliant with the study procedure and had available data were included. Renal clearance could not be assessed for ESRD participants. Participants originally assigned to the severe RI group were reassigned: 1 to the mild RI group (excluded from analysis), and 1 to the moderate RI group.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=7 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=4 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Parts 1 and 2] Estimated CLr of Gefapixant 50 mg in Participants With BSA Non-Normalized eGFR (Regression Analysis)	1.36 L/hr Interval 1.01 to 1.85	0.975 L/hr Interval 0.677 to 1.41	5.53 L/hr Interval 3.66 to 8.35	—	—

SECONDARY outcome

Timeframe: Parts 1 and 2 - Up to 29 days.

Population: All participants in Parts 1 and 2 who received at least one dose of the study drug.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Parts 1 and 2] Number of Participants Experiencing an Adverse Event (AE)	0 Participants	2 Participants	0 Participants	1 Participants	—

SECONDARY outcome

Timeframe: Part 1 and 2 - Up to 15 days

Population: All participants in Parts 1 and 2 who received at least one dose of the study drug.

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.

Outcome measures

Measure	[Part 1] Moderate RI n=6 Participants Participants with moderate RI received a single oral dose of gefapixant 50 mg	[Part 1] Severe RI n=6 Participants Participants with severe RI received a single oral dose of gefapixant 50 mg	[Part 2, Period 1] ESRD Non-HD n=6 Participants Participants with ESRD requiring HD, but not on HD, received a single oral dose of gefapixant 50 mg immediately after the scheduled HD, in Period 1	[Part 2, Period 2] ESRD HD n=6 Participants Participants with ESRD requiring HD, and on HD, received a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between gefapixant dose administrations in Periods 1 and 2, there was approximately a 7-day washout period with 3 dialysis sessions.	[Part 1 and Part 2] Healthy Controls Healthy participants were matched to participants with moderate and severe RI (Part 1) and participants with ESRD (Part 2).
[Parts 1 and 2] Number of Participants Discontinuing Study Treatment Due to an AE	0 Participants	0 Participants	0 Participants	0 Participants	—

Adverse Events

MK-7264 50 mg: Moderate RI

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

MK-7264 50 mg: Severe RI

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

MK-7264 50 mg: ESRD

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Controls

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	MK-7264 50 mg: Moderate RI n=6 participants at risk Participants with moderate RI received a single oral dose of gefapixant 50 mg	MK-7264 50 mg: Severe RI n=6 participants at risk Participants with severe RI received a single oral dose of gefapixant 50 mg	MK-7264 50 mg: ESRD n=6 participants at risk Participants with ESRD requiring HD received a single oral dose of gefapixant 50 mg immediately after HD in Period 1, followed by a single oral dose of gefapixant 50 mg two hours prior to HD in Period 2. Between the Periods 1 and 2 MK-7264 dose administrations there was approximately a 7-day washout period with 3 dialysis sessions.	Healthy Controls n=6 participants at risk Healthy control participants received a single oral dose of gefapixant 50 mg
Nervous system disorders Headache	0.00% 0/6 • Up to 29 days	0.00% 0/6 • Up to 29 days	0.00% 0/6 • Up to 29 days	16.7% 1/6 • Number of events 1 • Up to 29 days
Nervous system disorders Somnolence	0.00% 0/6 • Up to 29 days	16.7% 1/6 • Number of events 1 • Up to 29 days	0.00% 0/6 • Up to 29 days	0.00% 0/6 • Up to 29 days
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/6 • Up to 29 days	16.7% 1/6 • Number of events 1 • Up to 29 days	0.00% 0/6 • Up to 29 days	0.00% 0/6 • Up to 29 days

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place