Trial Outcomes & Findings for A Study of the Pharmacokinetics of Uprifosbuvir (MK-3682) and Ruzasvir (MK-8408) in Participants With Moderate and Severe Hepatic Insufficiency (MK-3682-029) (NCT NCT02666352)
NCT ID: NCT02666352
Last Updated: 2018-09-17
Results Overview
t1/2 is a measure of how long it takes to clear 50% of drug after reaching Cmax. The t1/2 for uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Pre-dose (0) and 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
Results posted on
2018-09-17
Participant Flow
Participants with moderate hepatic insufficiency (HI), severe HI, and healthy controls were recruited at 2 study centers in the United States.
Participant milestones
| Measure |
Moderate HI Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
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
A Study of the Pharmacokinetics of Uprifosbuvir (MK-3682) and Ruzasvir (MK-8408) in Participants With Moderate and Severe Hepatic Insufficiency (MK-3682-029)
Baseline characteristics by cohort
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
58.3 Years
STANDARD_DEVIATION 8.7 • n=99 Participants
|
55.4 Years
STANDARD_DEVIATION 8.2 • n=107 Participants
|
57.6 Years
STANDARD_DEVIATION 6.3 • n=206 Participants
|
57.1 Years
STANDARD_DEVIATION 7.5 • n=7 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
16 Participants
n=7 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 the mean plasma drug concentration from time of dosing to the last quantifiable sample. The AUC0-last for uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Time of the Last Quantifiable Sample (AUC0-last) of Uprifosbuvir
|
5.34 µM*hr
Interval 3.55 to 8.05
|
8.02 µM*hr
Interval 5.32 to 12.1
|
3.74 µM*hr
Interval 2.48 to 5.63
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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-inf is a measure of the mean plasma drug concentration from time of dosing to infinity. The AUC0-inf for uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Infinity (AUC0-inf) of Uprifosbuvir
|
5.39 µM*hr
Interval 3.57 to 8.12
|
8.09 µM*hr
Interval 5.37 to 12.2
|
3.76 µM*hr
Interval 2.5 to 5.68
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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.
AUC0-24hr is a measure of the mean plasma drug concentration from time of dosing to 24 hours post-dose. The AUC0-24hr for uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Area Under the Plasma Drug Concentration-Time Curve From Start of Dosing to 24 Hours Post-Dose (AUC0-24hr) of Uprifosbuvir
|
5.35 µM*hr
Interval 3.55 to 8.05
|
8.02 µM*hr
Interval 5.33 to 12.1
|
3.74 µM*hr
Interval 2.48 to 5.63
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 observed plasma drug concentration after dosing. The Cmax for uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Maximum Plasma Drug Concentration (Cmax) of Uprifosbuvir
|
1560 nM
Interval 1030.0 to 2360.0
|
2130 nM
Interval 1410.0 to 3240.0
|
1180 nM
Interval 778.0 to 1790.0
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: All participants are included in the analysis.
C24hr is a measure of plasma drug concentration 24 hours after dosing. The C24hr of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Plasma Drug Concentration at 24 Hours (C24hr) of Uprifosbuvir
|
7.01 nM
Interval 0.0 to 26.9
|
8.56 nM
Interval 0.0 to 85.5
|
2.55 nM
Interval 0.0 to 22.3
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 maximum plasma drug concentration (i.e., Cmax). The Tmax for uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Time to Reach Cmax (Tmax) of Uprifosbuvir
|
1.00 hr
Interval 0.5 to 4.0
|
0.50 hr
Interval 0.5 to 1.5
|
1.25 hr
Interval 0.5 to 3.0
|
PRIMARY outcome
Timeframe: Pre-dose (0) and 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 a measure of how long it takes to clear 50% of drug after reaching Cmax. The t1/2 for uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Apparent Terminal Half-Life (t1/2) of Uprifosbuvir
|
3.66 hr
Geometric Coefficient of Variation 21.7
|
3.56 hr
Geometric Coefficient of Variation 47.5
|
3.17 hr
Geometric Coefficient of Variation 38.5
|
PRIMARY outcome
Timeframe: Pre-dose (0) and 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 a measure of the apparent rate at which drug is removed from the body via renal, hepatic, and other clearance pathways after oral administration. The CL/F of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Apparent Total Clearance From Plasma After Oral Administration (CL/F) of Uprifosbuvir
|
153 L/hr
Geometric Coefficient of Variation 39.9
|
102 L/hr
Geometric Coefficient of Variation 61.1
|
219 L/hr
Geometric Coefficient of Variation 77.6
|
PRIMARY outcome
Timeframe: Pre-dose (0) and 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 during the terminal phase after non-intravenous administration. The Vz/F of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) of Uprifosbuvir
|
809 L
Geometric Coefficient of Variation 43.8
|
524 L
Geometric Coefficient of Variation 57.0
|
1000 L
Geometric Coefficient of Variation 83.0
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 the mean plasma drug concentration from time of dosing to the last quantifiable sample. The AUC0-last for the M5 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
AUC0-last of Uprifosbuvir Metabolite M5
|
6.46 µM*hr
Interval 4.9 to 8.52
|
6.79 µM*hr
Interval 5.15 to 8.95
|
8.11 µM*hr
Interval 6.15 to 10.7
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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-inf is a measure of the mean plasma drug concentration from time of dosing to infinity. The AUC0-inf for the M5 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
AUC0-inf of Uprifosbuvir Metabolite M5
|
6.78 µM*hr
Interval 5.15 to 8.93
|
7.22 µM*hr
Interval 5.48 to 9.5
|
8.44 µM*hr
Interval 6.41 to 11.1
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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.
AUC0-24hr is a measure of the mean plasma drug concentration from time of dosing to 24 hours post-dose. The AUC0-24hr for the M5 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
AUC0-24hr of Uprifosbuvir Metabolite M5
|
2.41 µM*hr
Interval 1.85 to 3.13
|
2.28 µM*hr
Interval 1.75 to 2.96
|
3.12 µM*hr
Interval 2.4 to 4.05
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 observed plasma drug concentration after dosing. The Cmax for the M5 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Cmax of Uprifosbuvir Metabolite M5
|
169 nM
Interval 130.0 to 220.0
|
151 nM
Interval 117.0 to 197.0
|
203 nM
Interval 156.0 to 264.0
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: All participants are included in the analysis.
C24hr is a measure of plasma drug concentration 24 hours after dosing. The C24hr of the M5 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
C24hr of Uprifosbuvir Metabolite M5
|
124 nM
Interval 93.9 to 164.0
|
122 nM
Interval 92.8 to 162.0
|
150 nM
Interval 114.0 to 198.0
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 a measure of the time delay between drug administration and the onset of absorption, where onset of absorption is defined as "the time point prior to the first observed/measured non-zero plasma concentration". The Tlag of the M5 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm (in this study Tlag was only calculated for the M5 uprifosbuvir metabolite).
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Lag Time (Tlag) for Uprifosbuvir Metabolite M5
|
3.00 hr
Interval 2.0 to 3.0
|
2.53 hr
Interval 2.0 to 3.0
|
2.00 hr
Interval 1.5 to 3.02
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 maximum plasma drug concentration (i.e., Cmax). The Tmax for the M5 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Tmax of Uprifosbuvir Metabolite M5
|
14.00 hr
Interval 12.0 to 18.0
|
16.00 hr
Interval 12.0 to 20.0
|
15.00 hr
Interval 10.0 to 16.0
|
PRIMARY outcome
Timeframe: Pre-dose (0) and 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.
Apparent t1/2 is a measure of how long it takes to clear 50% of drug after reaching Cmax. The t1/2 for the M5 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Apparent t1/2 of Uprifosbuvir Metabolite M5
|
24.09 hr
Geometric Coefficient of Variation 17.2
|
25.64 hr
Geometric Coefficient of Variation 19.2
|
23.59 hr
Geometric Coefficient of Variation 9.7
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 the mean plasma drug concentration from time of dosing to the last quantifiable sample. The AUC0-last for the M6 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
AUC0-last of Uprifosbuvir Metabolite M6
|
28.6 µM*hr
Interval 22.6 to 36.1
|
27.4 µM*hr
Interval 21.6 to 34.6
|
41.8 µM*hr
Interval 33.0 to 52.9
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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-inf is a measure of the mean plasma drug concentration from time of dosing to infinity. The AUC0-inf for the M6 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
AUC0-inf of Uprifosbuvir Metabolite M6
|
30.1 µM*hr
Interval 23.5 to 38.6
|
28.7 µM*hr
Interval 22.4 to 36.7
|
47.0 µM*hr
Interval 36.7 to 60.2
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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.
AUC0-24hr is a measure of the mean plasma drug concentration from time of dosing to 24 hours post-dose. The AUC0-24hr for the M6 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
AUC0-24hr of Uprifosbuvir Metabolite M6
|
13.1 µM*hr
Interval 10.6 to 16.1
|
13.2 µM*hr
Interval 10.8 to 16.3
|
16.6 µM*hr
Interval 13.5 to 20.4
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 observed plasma drug concentration after dosing. The Cmax for the M6 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Cmax of Uprifosbuvir Metabolite M6
|
851 nM
Interval 675.0 to 1070.0
|
834 nM
Interval 662.0 to 1050.0
|
1070 nM
Interval 846.0 to 1340.0
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: All participants are included in the analysis.
C24hr is a measure of plasma drug concentration 24 hours after dosing. The C24hr of the M6 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
C24hr of Uprifosbuvir Metabolite M6
|
402 nM
Interval 332.0 to 487.0
|
410 nM
Interval 339.0 to 497.0
|
564 nM
Interval 465.0 to 683.0
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 maximum plasma drug concentration (i.e., Cmax). The Tmax for the M6 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Tmax of Uprifosbuvir Metabolite M6
|
6.00 hr
Interval 2.0 to 12.0
|
4.00 hr
Interval 3.0 to 8.0
|
4.00 hr
Interval 3.0 to 6.0
|
PRIMARY outcome
Timeframe: Pre-dose (0) and 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.
Apparent t1/2 is a measure of how long it takes to clear 50% of drug after reaching Cmax. The t1/2 for the M6 metabolite of uprifosbuvir 450 mg (given in combination with ruzasvir 60 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Apparent t1/2 of Uprifosbuvir Metabolite M6
|
26.96 hr
Geometric Coefficient of Variation 19.4
|
26.45 hr
Geometric Coefficient of Variation 31.3
|
33.98 hr
Geometric Coefficient of Variation 37.7
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 the mean plasma drug concentration from time of dosing to the last quantifiable sample. The AUC0-last for ruzasvir 60 mg (given in combination with uprifosbuvir 450 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
AUC0-last of Ruzasvir
|
2.30 µM*hr
Interval 1.75 to 3.02
|
2.70 µM*hr
Interval 2.07 to 3.51
|
1.98 µM*hr
Interval 1.52 to 2.58
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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-inf is a measure of the mean plasma drug concentration from time of dosing to infinity. The AUC0-inf for ruzasvir 60 mg (given in combination with uprifosbuvir 450 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
AUC0-inf of Ruzasvir
|
2.60 µM*hr
Interval 1.99 to 3.41
|
3.32 µM*hr
Interval 2.56 to 4.31
|
2.10 µM*hr
Interval 1.62 to 2.73
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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.
AUC0-24hr is a measure of the mean plasma drug concentration from time of dosing to 24 hours post-dose. The AUC0-24hr for ruzasvir 60 mg (given in combination with uprifosbuvir 450 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
AUC0-24hr of Ruzasvir
|
1.04 µM*hr
Interval 0.729 to 1.49
|
1.05 µM*hr
Interval 0.744 to 1.48
|
1.17 µM*hr
Interval 0.83 to 1.65
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 observed plasma drug concentration after dosing. The Cmax for ruzasvir 60 mg (given in combination with uprifosbuvir 450 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Maximum Plasma Drug Concentration (Cmax) of Ruzasvir
|
105 nM
Interval 65.6 to 167.0
|
92.5 nM
Interval 58.9 to 145.0
|
137 nM
Interval 87.0 to 215.0
|
PRIMARY outcome
Timeframe: 24 hours post-dosePopulation: All participants are included in the analysis.
C24hr is a measure of plasma drug concentration 24 hours after dosing. The C24hr of ruzasvir 60 mg (given in combination with uprifosbuvir 450 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
C24hr of Ruzasvir
|
27.6 nM
Interval 21.4 to 35.7
|
32.4 nM
Interval 25.2 to 41.5
|
23.0 nM
Interval 18.0 to 29.5
|
PRIMARY outcome
Timeframe: Pre-dose (0), and 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 maximum plasma drug concentration (i.e., Cmax). The Tmax of ruzasvir 60 mg (given in combination with uprifosbuvir 450 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Tmax of Ruzasvir
|
3.00 hr
Interval 1.5 to 24.0
|
2.03 hr
Interval 1.5 to 4.0
|
3.00 hr
Interval 2.0 to 4.0
|
PRIMARY outcome
Timeframe: Pre-dose (0) and 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.
Apparent t1/2 is a measure of how long it takes to clear 50% of drug after reaching Cmax. The t1/2 for ruzasvir 60 mg (given in combination with uprifosbuvir 450 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Apparent t1/2 of Ruzasvir
|
38.08 hr
Geometric Coefficient of Variation 23.1
|
47.26 hr
Geometric Coefficient of Variation 36.6
|
30.43 hr
Geometric Coefficient of Variation 14.6
|
PRIMARY outcome
Timeframe: Pre-dose (0) and 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 a measure of the apparent rate at which drug is removed from the body via renal, hepatic, and other clearance pathways after oral administration. The CL/F of ruzasvir 60 mg (given in combination with uprifosbuvir 450 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
CL/F of Ruzasvir
|
28.4 L/hr
Geometric Coefficient of Variation 36.7
|
20.6 L/hr
Geometric Coefficient of Variation 52.8
|
32.6 L/hr
Geometric Coefficient of Variation 54.6
|
PRIMARY outcome
Timeframe: Pre-dose (0) and 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 during the terminal phase after non-intravenous administration. The Vz/F of ruzasvir 60 mg (given in combination with uprifosbuvir 450 mg) was calculated for each arm.
Outcome measures
| Measure |
Moderate HI Participants
n=8 Participants
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 Participants
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 Participants
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Vz/F of Ruzasvir
|
1560 L
Geometric Coefficient of Variation 49.8
|
1400 L
Geometric Coefficient of Variation 37.9
|
1430 L
Geometric Coefficient of Variation 48.1
|
Adverse Events
Moderate HI Participants
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Severe HI Participants
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Healthy Participants
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Moderate HI Participants
n=8 participants at risk
Participants with moderate HI (Child-Pugh score 7 to 9) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Severe HI Participants
n=8 participants at risk
Participants with severe HI (Child-Pugh score 10 to 15) received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
Healthy Participants
n=8 participants at risk
Participants with normal hepatic function received a single oral dose of 450 mg uprifosbuvir (3 x 150 mg tablets) and 60 mg ruzasvir (6 x 10 mg capsules) following an overnight fast.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
|
Gastrointestinal disorders
Flatulence
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
|
Nervous system disorders
Dizziness
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
|
Nervous system disorders
Hepatic encephalopathy
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
|
Nervous system disorders
Headache
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
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 participants are included in the safety analysis.
|
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