Trial Outcomes & Findings for The Pharmacokinetics of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Participants With Renal Insufficiency (MK-5172-050) (NCT NCT01937975)

Results Overview

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

Up to 24 hours postdose

Results posted on

2019-06-12

Participant Flow

After enrollment of participants with End Stage Renal Disease and Severe Renal Impairment, healthy participants with matching mean age, body mass index, and gender were enrolled.

Participant milestones

Participant milestones
Measure	Healthy Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease on Hemodialysis Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With Severe Renal Impairment Participants with Severe Renal Impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.
Overall Study STARTED	8	8	8
Overall Study COMPLETED	8	8	8
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Pharmacokinetics of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Participants With Renal Insufficiency (MK-5172-050)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Participants With End Stage Renal Disease on Hemodialysis n=8 Participants Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With Severe Renal Impairment n=8 Participants Participants with Severe Renal Impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Total n=24 Participants Total of all reporting groups
Age, Continuous	47.8 Years n=5 Participants	65.8 Years n=7 Participants	55.1 Years n=5 Participants	56.2 Years n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Estimated Glomerular Filtration Rate	NA mL/min/1.73 m^2 n=5 Participants	18.0 mL/min/1.73 m^2 n=7 Participants	93.4 mL/min/1.73 m^2 n=5 Participants	NA mL/min/1.73 m^2 n=4 Participants

PRIMARY outcome

Timeframe: Up to 24 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir Day 9	NA uM*hr No pharmacokinetic sampling on Day 9 for this group	NA uM*hr No pharmacokinetic sampling on Day 9 for this group	0.969 uM*hr Interval 0.689 to 1.36
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir Day 10	1.88 uM*hr Interval 1.23 to 2.86	1.14 uM*hr Interval 0.843 to 1.54	0.944 uM*hr Interval 0.671 to 1.33

PRIMARY outcome

Timeframe: 24 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Grazoprevir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir Day 9	NA nM No pharmacokinetic sampling on Day 9 for this group	NA nM No pharmacokinetic sampling on Day 9 for this group	11.4 nM Interval 8.16 to 16.1
Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir Day 10	23.3 nM Interval 15.4 to 35.2	14.5 nM Interval 10.7 to 19.6	11.3 nM Interval 8.03 to 15.8

PRIMARY outcome

Timeframe: Up to 120 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Maximum Plasma Concentration (Cmax) of Grazoprevir Day 9	NA uM No pharmacokinetic sampling on Day 9 for this group	NA uM No pharmacokinetic sampling on Day 9 for this group	0.141 uM Interval 0.092 to 0.215
Maximum Plasma Concentration (Cmax) of Grazoprevir Day 10	0.255 uM Interval 0.152 to 0.429	0.154 uM Interval 0.106 to 0.224	0.135 uM Interval 0.088 to 0.206

PRIMARY outcome

Timeframe: Up to 120 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Time of Maximum Plasma Concentration (Tmax) of Grazoprevir Day 9	NA Hours No pharmacokinetic sampling on Day 9 for this group	NA Hours No pharmacokinetic sampling on Day 9 for this group	2.00 Hours Interval 1.0 to 6.0
Time of Maximum Plasma Concentration (Tmax) of Grazoprevir Day 10	3.00 Hours Interval 0.5 to 6.0	2.50 Hours Interval 1.0 to 6.0	2.50 Hours Interval 0.5 to 7.0

PRIMARY outcome

Timeframe: Up to 120 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model. End Stage Renal Disease for Non-HD Day 9 was not reported since only 24-hour collections were made on that day.

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Apparent Terminal Half-life (T1/2) of Grazoprevir	36.30 Hours Geometric Coefficient of Variation 30.53 • Interval 1.0 to 6.0	35.18 Hours Geometric Coefficient of Variation 19.64	28.38 Hours Geometric Coefficient of Variation 20.88 • Interval 0.5 to 6.0

PRIMARY outcome

Timeframe: Up to 24 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir Day 9	NA Liters/hr No pharmacokinetic sampling on Day 9 for this group	NA Liters/hr No pharmacokinetic sampling on Day 9 for this group	135 Liters/hr Interval 95.6 to 189.0
Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir Day 10	69.4 Liters/hr Interval 45.6 to 106.0	114 Liters/hr Interval 84.5 to 155.0	138 Liters/hr Interval 98.1 to 194.0

PRIMARY outcome

Timeframe: Up to 24 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model. End Stage Renal Disease for Non-HD Day 9 was not reported since only 24-hour collections were made on that day.

Blood for determination of Grazoprevir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir	3490 Liters Interval 2320.0 to 5260.0	5760 Liters Interval 4180.0 to 7930.0	5430 Liters Interval 3660.0 to 8050.0

PRIMARY outcome

Timeframe: Up to 24 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir Day 9	NA uM*hr No pharmacokinetic sampling on Day 9 for this group	NA uM*hr No pharmacokinetic sampling on Day 9 for this group	1.89 uM*hr Interval 1.48 to 2.42
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir Day 10	4.07 uM*hr Interval 3.01 to 5.52	2.19 uM*hr Interval 1.76 to 2.72	2.16 uM*hr Interval 1.69 to 2.77

PRIMARY outcome

Timeframe: 24 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Elbasvir concentration was collected at 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir Day 9	NA nM No pharmacokinetic sampling on Day 9 for this group	NA nM No pharmacokinetic sampling on Day 9 for this group	46.9 nM Interval 35.2 to 62.4
Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir Day 10	126 nM Interval 88.6 to 179.0	60.9 nM Interval 47.3 to 78.5	58.2 nM Interval 43.7 to 77.5

PRIMARY outcome

Timeframe: Up to 120 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Maximum Plasma Concentration (Cmax) of Elbasvir Day 9	NA uM No pharmacokinetic sampling on Day 9 for this group	NA uM No pharmacokinetic sampling on Day 9 for this group	0.137 uM Interval 0.105 to 0.178
Maximum Plasma Concentration (Cmax) of Elbasvir Day 10	0.271 uM Interval 0.196 to 0.373	0.163 uM Interval 0.129 to 0.206	0.154 uM Interval 0.118 to 0.2

PRIMARY outcome

Timeframe: Up to 120 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10 (all participants) and only up to 24 hours for ESRD participants on Day 9

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Time of Maximum Plasma Concentration (Tmax) of Elbasvir Day 9	NA Hours No pharmacokinetic sampling on Day 9 for this group	NA Hours No pharmacokinetic sampling on Day 9 for this group	4.00 Hours Interval 3.0 to 4.0
Time of Maximum Plasma Concentration (Tmax) of Elbasvir Day 10	4.00 Hours Interval 4.0 to 6.0	4.00 Hours Interval 2.0 to 4.0	5.00 Hours Interval 3.0 to 5.0

PRIMARY outcome

Timeframe: Up to 120 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model. End Stage Renal Disease for Non-HD Day 9 was not reported since only 24-hour collections were made on that day.

Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, 24, 32, 48, 72, 96, and 120 hours postdose on Day 10

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=7 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Apparent Terminal Half-life (T1/2) of Elbasvir	28.97 Hours Geometric Coefficient of Variation 18.26 • Interval 1.0 to 6.0	25.02 Hours Geometric Coefficient of Variation 19.08	23.04 Hours Geometric Coefficient of Variation 6.34 • Interval 0.5 to 6.0

PRIMARY outcome

Timeframe: Up to 24 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model.

Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 9 (ESRD participants only) or Day 10 (all participants)

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=8 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir Day 9	NA Liters/hr No pharmacokinetic sampling on Day 9 for this group	NA Liters/hr No pharmacokinetic sampling on Day 9 for this group	29.9 Liters/hr Interval 23.4 to 38.3
Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir Day 10	13.9 Liters/hr Interval 10.3 to 18.9	25.9 Liters/hr Interval 20.8 to 32.2	26.2 Liters/hr Interval 20.5 to 33.5

PRIMARY outcome

Timeframe: Up to 24 hours postdose

Population: The Per Protocol population included all participants who complied with the protocol sufficiently to ensure that these data likely to exhibit the effects of treatment, according to the underlying scientific model. End Stage Renal Disease for Non-HD Day 9 was not reported since only 24-hour collections were made on that day.

Blood for determination of Elbasvir concentration was collected predose and 0.5, 1, 2, 3, 4, 5, 5.5, 6, 7, 8, 12, 16, and 24 hours postdose on Day 10

Outcome measures

Outcome measures
Measure	Participants With Severe Renal Impairment: Day 10 n=8 Participants Participants with Severe Renal Impairment (SRI, estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants: Day 10 n=7 Participants Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With End Stage Renal Disease n=8 Participants Participants with End Stage Renal Disease (ESRD) on hemodialysis (HD) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days. Day 9 was a non-hemodialysis day for these participants. On Day 10, hemodialysis for these participants was timed to occur after the median Tmax (\~5 hours postdose).
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir	569 Liters Interval 420.0 to 772.0	901 Liters Interval 699.0 to 1160.0	857 Liters Interval 641.0 to 1150.0

Adverse Events

Participants With End Stage Renal Disease on Hemodialysis

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Participants With Severe Renal Impairment

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Healthy Participants

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Participants With End Stage Renal Disease on Hemodialysis n=8 participants at risk Participants with End Stage Renal Disease on hemodialysis received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Participants With Severe Renal Impairment n=8 participants at risk Participants with Severe Renal Impairment (estimated glomerular filtration rate \<30 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.	Healthy Participants n=8 participants at risk Healthy participants (estimated glomerular filtration rate \>=80 mL/min/1.73 m\^2) received once daily Grazoprevir 100 mg tablet and Elbasvir 50 mg tablet for 10 days.
Gastrointestinal disorders Dry mouth	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)
Gastrointestinal disorders Nausea	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)
Gastrointestinal disorders Paraesthesia oral	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)
Gastrointestinal disorders Vomiting	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)
Infections and infestations Upper respiratory tract infection	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)
Musculoskeletal and connective tissue disorders Muscular weakness	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)
Musculoskeletal and connective tissue disorders Myalgia	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)
Nervous system disorders Headache	37.5% 3/8 • Number of events 3 • Up to 14 days after the last dose of study drug (up to 24 days)	25.0% 2/8 • Number of events 2 • Up to 14 days after the last dose of study drug (up to 24 days)	25.0% 2/8 • Number of events 2 • Up to 14 days after the last dose of study drug (up to 24 days)
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)	0.00% 0/8 • Up to 14 days after the last dose of study drug (up to 24 days)	12.5% 1/8 • Number of events 1 • Up to 14 days after the last dose of study drug (up to 24 days)

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme, Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor will provide separate guidance on the criteria for publication of clinical trial data when contacted for permission to publish.
Publication restrictions are in place

Restriction type: OTHER