Trial Outcomes & Findings for The Pharmacokinetics of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Participants With Renal Insufficiency (MK-5172-050) (NCT NCT01937975)
NCT ID: NCT01937975
Last Updated: 2019-06-12
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)
COMPLETED
PHASE1
24 participants
Up to 24 hours postdose
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
| Measure |
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.
|
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.
|
|---|---|---|---|
|
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
| 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=99 Participants
|
65.8 Years
n=107 Participants
|
55.1 Years
n=206 Participants
|
56.2 Years
n=7 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
11 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
13 Participants
n=7 Participants
|
|
Estimated Glomerular Filtration Rate
|
NA mL/min/1.73 m^2
n=99 Participants
|
18.0 mL/min/1.73 m^2
n=107 Participants
|
93.4 mL/min/1.73 m^2
n=206 Participants
|
NA mL/min/1.73 m^2
n=7 Participants
|
PRIMARY outcome
Timeframe: Up to 24 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir
Day 9
|
0.969 uM*hr
Interval 0.689 to 1.36
|
NA uM*hr
No pharmacokinetic sampling on Day 9 for this group
|
NA uM*hr
No pharmacokinetic sampling on Day 9 for this group
|
|
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Grazoprevir
Day 10
|
0.944 uM*hr
Interval 0.671 to 1.33
|
1.88 uM*hr
Interval 1.23 to 2.86
|
1.14 uM*hr
Interval 0.843 to 1.54
|
PRIMARY outcome
Timeframe: 24 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir
Day 9
|
11.4 nM
Interval 8.16 to 16.1
|
NA nM
No pharmacokinetic sampling on Day 9 for this group
|
NA nM
No pharmacokinetic sampling on Day 9 for this group
|
|
Plasma Concentration at 24 Hours Postdose (C24hr) of Grazoprevir
Day 10
|
11.3 nM
Interval 8.03 to 15.8
|
23.3 nM
Interval 15.4 to 35.2
|
14.5 nM
Interval 10.7 to 19.6
|
PRIMARY outcome
Timeframe: Up to 120 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Grazoprevir
Day 9
|
0.141 uM
Interval 0.092 to 0.215
|
NA uM
No pharmacokinetic sampling on Day 9 for this group
|
NA uM
No pharmacokinetic sampling on Day 9 for this group
|
|
Maximum Plasma Concentration (Cmax) of Grazoprevir
Day 10
|
0.135 uM
Interval 0.088 to 0.206
|
0.255 uM
Interval 0.152 to 0.429
|
0.154 uM
Interval 0.106 to 0.224
|
PRIMARY outcome
Timeframe: Up to 120 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Grazoprevir
Day 9
|
2.00 Hours
Interval 1.0 to 6.0
|
NA Hours
No pharmacokinetic sampling on Day 9 for this group
|
NA Hours
No pharmacokinetic sampling on Day 9 for this group
|
|
Time of Maximum Plasma Concentration (Tmax) of Grazoprevir
Day 10
|
2.50 Hours
Interval 0.5 to 7.0
|
3.00 Hours
Interval 0.5 to 6.0
|
2.50 Hours
Interval 1.0 to 6.0
|
PRIMARY outcome
Timeframe: Up to 120 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Apparent Terminal Half-life (T1/2) of Grazoprevir
|
28.38 Hours
Geometric Coefficient of Variation 20.88 • Interval 0.5 to 6.0
|
36.30 Hours
Geometric Coefficient of Variation 30.53 • Interval 1.0 to 6.0
|
35.18 Hours
Geometric Coefficient of Variation 19.64
|
PRIMARY outcome
Timeframe: Up to 24 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir
Day 9
|
135 Liters/hr
Interval 95.6 to 189.0
|
NA Liters/hr
No pharmacokinetic sampling on Day 9 for this group
|
NA Liters/hr
No pharmacokinetic sampling on Day 9 for this group
|
|
Apparent Clearance After Extravascular Administration (CL/F) of Grazoprevir
Day 10
|
138 Liters/hr
Interval 98.1 to 194.0
|
69.4 Liters/hr
Interval 45.6 to 106.0
|
114 Liters/hr
Interval 84.5 to 155.0
|
PRIMARY outcome
Timeframe: Up to 24 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Grazoprevir
|
5430 Liters
Interval 3660.0 to 8050.0
|
3490 Liters
Interval 2320.0 to 5260.0
|
5760 Liters
Interval 4180.0 to 7930.0
|
PRIMARY outcome
Timeframe: Up to 24 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir
Day 10
|
2.16 uM*hr
Interval 1.69 to 2.77
|
4.07 uM*hr
Interval 3.01 to 5.52
|
2.19 uM*hr
Interval 1.76 to 2.72
|
|
Area Under the Concentration-time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Elbasvir
Day 9
|
1.89 uM*hr
Interval 1.48 to 2.42
|
NA uM*hr
No pharmacokinetic sampling on Day 9 for this group
|
NA uM*hr
No pharmacokinetic sampling on Day 9 for this group
|
PRIMARY outcome
Timeframe: 24 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir
Day 9
|
46.9 nM
Interval 35.2 to 62.4
|
NA nM
No pharmacokinetic sampling on Day 9 for this group
|
NA nM
No pharmacokinetic sampling on Day 9 for this group
|
|
Plasma Concentration at 24 Hours Postdose (C24hr) of Elbasvir
Day 10
|
58.2 nM
Interval 43.7 to 77.5
|
126 nM
Interval 88.6 to 179.0
|
60.9 nM
Interval 47.3 to 78.5
|
PRIMARY outcome
Timeframe: Up to 120 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Elbasvir
Day 9
|
0.137 uM
Interval 0.105 to 0.178
|
NA uM
No pharmacokinetic sampling on Day 9 for this group
|
NA uM
No pharmacokinetic sampling on Day 9 for this group
|
|
Maximum Plasma Concentration (Cmax) of Elbasvir
Day 10
|
0.154 uM
Interval 0.118 to 0.2
|
0.271 uM
Interval 0.196 to 0.373
|
0.163 uM
Interval 0.129 to 0.206
|
PRIMARY outcome
Timeframe: Up to 120 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) of Elbasvir
Day 9
|
4.00 Hours
Interval 3.0 to 4.0
|
NA Hours
No pharmacokinetic sampling on Day 9 for this group
|
NA Hours
No pharmacokinetic sampling on Day 9 for this group
|
|
Time of Maximum Plasma Concentration (Tmax) of Elbasvir
Day 10
|
5.00 Hours
Interval 3.0 to 5.0
|
4.00 Hours
Interval 4.0 to 6.0
|
4.00 Hours
Interval 2.0 to 4.0
|
PRIMARY outcome
Timeframe: Up to 120 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Apparent Terminal Half-life (T1/2) of Elbasvir
|
23.04 Hours
Geometric Coefficient of Variation 6.34 • Interval 0.5 to 6.0
|
28.97 Hours
Geometric Coefficient of Variation 18.26 • Interval 1.0 to 6.0
|
25.02 Hours
Geometric Coefficient of Variation 19.08
|
PRIMARY outcome
Timeframe: Up to 24 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir
Day 9
|
29.9 Liters/hr
Interval 23.4 to 38.3
|
NA Liters/hr
No pharmacokinetic sampling on Day 9 for this group
|
NA Liters/hr
No pharmacokinetic sampling on Day 9 for this group
|
|
Apparent Clearance After Extravascular Administration (CL/F) of Elbasvir
Day 10
|
26.2 Liters/hr
Interval 20.5 to 33.5
|
13.9 Liters/hr
Interval 10.3 to 18.9
|
25.9 Liters/hr
Interval 20.8 to 32.2
|
PRIMARY outcome
Timeframe: Up to 24 hours postdosePopulation: 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
| Measure |
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).
|
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.
|
|---|---|---|---|
|
Apparent Volume of Distribution After Extravascular Administration (Vz/F) of Elbasvir
|
857 Liters
Interval 641.0 to 1150.0
|
569 Liters
Interval 420.0 to 772.0
|
901 Liters
Interval 699.0 to 1160.0
|
Adverse Events
Participants With End Stage Renal Disease on Hemodialysis
Participants With Severe Renal Impairment
Healthy Participants
Serious adverse events
Adverse event data not reported
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.
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