Trial Outcomes & Findings for Pharmacokinetics of MK-3682B in Participants With Moderate to Severe Renal Insufficiency (MK-3682B-030) (NCT NCT02661126)
NCT ID: NCT02661126
Last Updated: 2019-01-09
Results Overview
AUC0-last is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to the time of the last quantifiable (\< lower limit of quantification \[LLOQ\]) sample following oral administration of MK-3682B.
COMPLETED
PHASE1
16 participants
0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
2019-01-09
Participant Flow
In Part 1, adults with moderate renal impairment (RI; determined by estimated glomerular filtration rate \[eGFR\]), and healthy participants, were recruited at 2 sites in the US. Part 2 was intended to enroll severe RI participants but was not conducted based on results of a planned interim analysis of Part 1 data.
Participant milestones
| Measure |
Moderate RI Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B fixed dose combination (FDC) tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
Healthy participants (creatinine clearance \[CLcr\] ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics of MK-3682B in Participants With Moderate to Severe Renal Insufficiency (MK-3682B-030)
Baseline characteristics by cohort
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
69.6 Years
STANDARD_DEVIATION 9.0 • n=39 Participants
|
65.8 Years
STANDARD_DEVIATION 2.6 • n=41 Participants
|
67.7 Years
STANDARD_DEVIATION 6.7 • n=35 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=39 Participants
|
2 Participants
n=41 Participants
|
4 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=39 Participants
|
6 Participants
n=41 Participants
|
12 Participants
n=35 Participants
|
|
Body Mass Index (BMI)
|
30.32 kg/m^2
STANDARD_DEVIATION 4.023 • n=39 Participants
|
30.11 kg/m^2
STANDARD_DEVIATION 2.057 • n=41 Participants
|
30.22 kg/m^2
STANDARD_DEVIATION 3.088 • n=35 Participants
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
AUC0-last is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to the time of the last quantifiable (\< lower limit of quantification \[LLOQ\]) sample following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682)
|
8.55 uM*hr
Interval 6.22 to 11.8
|
4.23 uM*hr
Interval 3.08 to 5.82
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
AUC0-∞ is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir
|
8.56 uM*hr
Interval 6.24 to 11.7
|
4.28 uM*hr
Interval 3.12 to 5.87
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dosePopulation: All participants are included in the analysis.
AUC0-24 is a measure of total exposure to uprifosbuvir in plasma from dosing to 24 hours following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir
|
8.54 uM*hr
Interval 6.22 to 11.7
|
4.24 uM*hr
Interval 3.08 to 5.82
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
Cmax is the maximum amount of uprifosbuvir in plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Uprifosbuvir
|
3030 nM
Interval 2230.0 to 4110.0
|
1570 nM
Interval 1160.0 to 2130.0
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: All Healthy Control participants are included in the analysis. Since \>50% of participants in the Moderate RI group had C24 values \<LLOQ, no data are presented for this group as per Merck policy.
C24 is the plasma concentration of uprifosbuvir 24 hours following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir
|
—
|
3.65 nM
Interval 0.0 to 9.97
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis
Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir
|
1.00 Hours
Interval 0.5 to 4.0
|
1.00 Hours
Interval 0.5 to 2.0
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
CL/F is the apparent total body clearance of uprifosbuvir following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Apparent Total Body Clearance (CL/F) of Uprifosbuvir
|
96.3 Liters/hour
Geometric Coefficient of Variation 51.5
|
193 Liters/hour
Geometric Coefficient of Variation 34.7
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
Vz/F is the apparent volume of distribution of uprifosbuvir following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Apparent Volume of Distribution (Vz/F) of Uprifosbuvir
|
290 Liters
Geometric Coefficient of Variation 51.7
|
724 Liters
Geometric Coefficient of Variation 115.2
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
t1/2 is the amount of time required to clear 50% of uprifosbuvir from plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir
|
2.09 Hours
Geometric Coefficient of Variation 65.6
|
2.60 Hours
Geometric Coefficient of Variation 92.9
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
AUC0-last is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-last of Uprifosbuvir Metabolite M5
|
14.8 uM*hr
Interval 11.1 to 19.6
|
7.62 uM*hr
Interval 5.74 to 10.1
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-∞ of Uprifosbuvir Metabolite M5
|
16.2 uM*hr
Interval 12.5 to 20.8
|
7.99 uM*hr
Interval 6.19 to 10.3
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dosePopulation: All participants are included in the analysis.
AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from dosing to 24 hours following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-24 of Uprifosbuvir Metabolite M5
|
4.59 uM*hr
Interval 3.25 to 6.47
|
2.67 uM*hr
Interval 1.89 to 3.77
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
Cmax is the maximum amount of uprifosbuvir metabolite M5 in plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Cmax of Uprifosbuvir Metabolite M5
|
321 nM
Interval 220.0 to 467.0
|
173 nM
Interval 119.0 to 252.0
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: All participants are included in the analysis.
C24 is the plasma concentration of uprifosbuvir metabolite M5 24 hours following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
C24 of Uprifosbuvir Metabolite M5
|
262 nM
Interval 189.0 to 365.0
|
129 nM
Interval 93.0 to 180.0
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis
Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M5 following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Tmax of Uprifosbuvir Metabolite M5
|
20.00 Hours
Interval 10.0 to 24.0
|
13.00 Hours
Interval 12.0 to 16.0
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis
Tlag is the time from dosing to first appearance in plasma of uprifosbuvir metabolite M5 following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Lag Time (Tlag) of Uprifosbuvir Metabolite M5
|
2.00 Hours
Interval 2.0 to 3.0
|
2.00 Hours
Interval 2.0 to 3.0
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M5 from plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
t½ of Uprifosbuvir Metabolite M5
|
26.27 Hours
Geometric Coefficient of Variation 45.0
|
25.33 Hours
Geometric Coefficient of Variation 6.4
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
AUC0-last is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-last of Uprifosbuvir Metabolite M6
|
63.9 uM*hr
Interval 50.1 to 81.5
|
33.5 uM*hr
Interval 26.3 to 42.8
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-∞ of Uprifosbuvir Metabolite M6
|
71.4 uM*hr
Interval 55.8 to 91.3
|
36.2 uM*hr
Interval 28.3 to 46.2
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dosePopulation: All participants are included in the analysis.
AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from dosing to 24 hours following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-24 of Uprifosbuvir Metabolite M6
|
27.2 uM*hr
Interval 22.2 to 33.4
|
13.9 uM*hr
Interval 11.3 to 17.1
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
Cmax is the maximum amount of uprifosbuvir metabolite M6 in plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Cmax of Uprifosbuvir Metabolite M6
|
1540 nM
Interval 1210.0 to 1950.0
|
906 nM
Interval 715.0 to 1150.0
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: All participants are included in the analysis.
C24 is the plasma concentration of uprifosbuvir metabolite M6 24 hours following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
C24 of Uprifosbuvir Metabolite M6
|
905 nM
Interval 712.0 to 1150.0
|
466 nM
Interval 367.0 to 592.0
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis
Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M6 following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Tmax of Uprifosbuvir Metabolite M6
|
8.00 Hours
Interval 3.0 to 10.0
|
3.50 Hours
Interval 3.0 to 4.0
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M6 from plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
t½ of Uprifosbuvir Metabolite M6
|
33.58 Hours
Geometric Coefficient of Variation 39.7
|
30.55 Hours
Geometric Coefficient of Variation 19.7
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
AUC0-last is a measure of total exposure to grazoprevir in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-last of Grazoprevir (MK-5172)
|
0.974 uM*hr
Interval 0.523 to 1.81
|
0.730 uM*hr
Interval 0.392 to 1.36
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants except 1 are included in the analysis. One participant in the Moderate RI group did not have a well characterized terminal phase and their value was set to "missing".
AUC0-∞ is a measure of total exposure to grazoprevir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=7 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-∞ of Grazoprevir
|
1.32 uM*hr
Interval 0.708 to 2.45
|
0.826 uM*hr
Interval 0.463 to 1.48
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dosePopulation: All participants are included in the analysis.
AUC0-24 is a measure of total exposure to grazoprevir in plasma from the start of dosing to 24 hours post-dose following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-24 of Grazoprevir
|
0.436 uM*hr
Interval 0.218 to 0.875
|
0.380 uM*hr
Interval 0.19 to 0.762
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
Cmax is the maximum amount of grazoprevir in plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Cmax of Grazoprevir
|
67.5 nM
Interval 31.0 to 147.0
|
54.7 nM
Interval 25.1 to 119.0
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: All participants are included in the analysis.
C24 is the plasma concentration of grazoprevir 24 hours following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
C24 of Grazoprevir
|
9.41 nM
Interval 4.64 to 19.1
|
7.36 nM
Interval 3.63 to 14.9
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis
Tmax is the time required to reach the maximum post-dose plasma concentration of grazoprevir following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Tmax of Grazoprevir
|
2.00 Hours
Interval 1.0 to 4.0
|
2.25 Hours
Interval 1.0 to 10.0
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants except 1 are included in the analysis. One participant in the Moderate RI group did not have a well characterized terminal phase and their value was set to "missing".
CL/F is the apparent total body clearance of grazoprevir following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=7 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
CL/F of Grazoprevir
|
99.1 Liters/hour
Geometric Coefficient of Variation 122.0
|
158 Liters/hour
Geometric Coefficient of Variation 57.9
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants except 1 are included in the analysis. One participant in the Moderate RI group did not have a well characterized terminal phase and their value was set to "missing".
Vz/F is the apparent volume of distribution of grazoprevir following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=7 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Vz/F of Grazoprevir
|
6030 Liters
Geometric Coefficient of Variation 183.5
|
9750 Liters
Geometric Coefficient of Variation 77.5
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants except 1 are included in the analysis. One participant in the Moderate RI group did not have a well characterized terminal phase and their value was set to "missing".
t1/2 is the amount of time required to clear 50% of grazoprevir from plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=7 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
t½ of Grazoprevir
|
42.21 Hours
Geometric Coefficient of Variation 40.3
|
42.85 Hours
Geometric Coefficient of Variation 26.4
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
AUC0-last is a measure of total exposure to ruzasvir in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-last of Ruzasvir (MK-8408)
|
2.07 uM*hr
Interval 1.6 to 2.67
|
1.32 uM*hr
Interval 1.03 to 1.71
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
AUC0-∞ is a measure of total exposure to ruzasvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-∞ of Ruzasvir
|
2.19 uM*hr
Interval 1.71 to 2.81
|
1.40 uM*hr
Interval 1.09 to 1.79
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dosePopulation: All participants are included in the analysis.
AUC0-24 is a measure of total exposure to ruzasvir in plasma from dosing to 24 hours following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
AUC0-24 of Ruzasvir
|
1.11 uM*hr
Interval 0.872 to 1.42
|
0.744 uM*hr
Interval 0.583 to 0.948
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
Cmax is the maximum amount of ruzasvir in plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Cmax of Ruzasvir
|
117 nM
Interval 88.9 to 154.0
|
80.9 nM
Interval 61.6 to 106.0
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: All participants are included in the analysis.
C24 is the plasma concentration of ruzasvir 24 hours following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
C24 of Ruzasvir
|
23.9 nM
Interval 18.5 to 30.8
|
15.5 nM
Interval 12.0 to 20.0
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis
Tmax is the time required to reach the maximum post-dose plasma concentration of ruzasvir following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Tmax of Ruzasvir
|
3.00 Hours
Interval 1.5 to 4.0
|
3.00 Hours
Interval 2.0 to 4.0
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
CL/F is the apparent total body clearance of ruzasvir following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
CL/F of Ruzasvir
|
31.0 Liters/hour
Geometric Coefficient of Variation 34.5
|
48.8 Liters/hour
Geometric Coefficient of Variation 31.2
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
Vz/F is the apparent volume of distribution of ruzasvir following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Vz/F of Ruzasvir
|
1410 Liters
Geometric Coefficient of Variation 40.0
|
2060 Liters
Geometric Coefficient of Variation 26.9
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dosePopulation: All participants are included in the analysis.
t1/2 is the amount of time required to clear 50% of ruzasvir from plasma following oral administration of MK-3682B.
Outcome measures
| Measure |
Moderate RI Participants
n=8 Participants
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 Participants
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
t½ of Ruzasvir
|
31.50 Hours
Geometric Coefficient of Variation 11.4
|
29.31 Hours
Geometric Coefficient of Variation 7.0
|
Adverse Events
Moderate RI Participants
Healthy Participants
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Moderate RI Participants
n=8 participants at risk
Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
Healthy Participants
n=8 participants at risk
Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • Number of events 1 • Up to 14 days
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All 16 participants were included in the safety and tolerability assessment.
|
0.00%
0/8 • Up to 14 days
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All 16 participants were included in the safety and tolerability assessment.
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
1/8 • Number of events 1 • Up to 14 days
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All 16 participants were included in the safety and tolerability assessment.
|
12.5%
1/8 • Number of events 1 • Up to 14 days
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All 16 participants were included in the safety and tolerability assessment.
|
|
Nervous system disorders
Headache
|
25.0%
2/8 • Number of events 2 • Up to 14 days
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All 16 participants were included in the safety and tolerability assessment.
|
0.00%
0/8 • Up to 14 days
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All 16 participants were included in the safety and tolerability assessment.
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Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place