Hepatitis C, Chronic
Conditions
Brief summary
This is a non-randomized, open-label, single-dose study to evaluate the pharmacokinetics (PK) of uprifosbuvir (MK-3682), the M5 and M6 metabolites of uprifosbuvir, and ruzasvir (MK-8408), in participants with moderate hepatic insufficiency (HI), participants with severe HI, and age-matched healthy control participants.
Interventions
DRUGUprifosbuvir
A single dose of uprifosbuvir 450 mg (given as three 150-mg tablets) taken by mouth.
DRUGRuzasvir
A single dose of ruzasvir 60 mg (given as six 10-mg capsules) taken by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
HI Participants Only: * Has a diagnosis of chronic (\>6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) HI features of cirrhosis; * Part 1 only: Participant's score on the Child-Pugh scale ranges from 7 to 9 (moderate HI) at study start. * Part 2 only: Participant's score on the Child-Pugh scale ranges from 10 to 15 (severe HI) at study start. All Participants: * Body mass index (BMI) ≥19 and ≤ 40 kg/m\^2; * Continuous non-smokers or moderate smokers (of fewer than 20 cigarettes/day or the equivalent). Participants must agree to consume no more than 10 cigarettes or equivalent/day from the time of screening and throughout the period of sample collection; * Health is judged to be stable based on medical history (except for the hepatic impairment condition), physical examination, vital signs, electrocardiogram (ECGs), and laboratory safety tests; * For female participants of childbearing potential: either sexually inactive for 14 days prior to study start and throughout study or be using an acceptable birth control method; * Female participants who are sexually inactive, but become sexually active during the course of the study must agree to use a double physical barrier method (e.g., condom and diaphragm) and a chemical barrier (e.g., spermicide) from the time of the start of sexual activity through completion of the study; * Vasectomized or non-vasectomized male participants must agree to use a condom with spermicide or abstain from sexual intercourse from dosing until 90 days after dosing; * Male participants must agree not to donate sperm from dosing until 90 days after dosing; * Able to swallow multiple tablets and capsules.
Exclusion criteria
HI Participants Only: * Presence of moderate or severe renal insufficiency (estimated glomerular filtration rate \[eGFR\] ≤50 mL/min/1.73 m\^2 calculated according to the Modification of Diet in Renal Disease \[MDRD\] study equation); * Presence of drug abuse within the past 6 months prior to dosing. Healthy Participants Only: * Presence of moderate or severe renal insufficiency (eGFR ≤60 mL/min/1.73 m\^2 calculated according to the MDRD study equation); * History or presence of alcoholism or drug abuse within the past 2 years prior to dosing; All Participants: * Is mentally or legally incapacitated or has significant emotional problems at the time of study start or expected during the study; * History or presence of clinically significant medical or psychiatric condition or disease; * History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds; * Female participants who are pregnant or lactating; * Positive results at study start for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV); * Unable to refrain from or anticipates the use of any medication or substance (including prescription or over-the-counter, vitamin supplements, natural or herbal supplements) for the prohibited time period; * Has taken amiodarone at any time in their life; * Donation of blood \>500 mL or had significant blood loss within 56 days prior to the dose of study drugs; * Plasma donation within 7 days prior to the dose of study drugs; * Dosed in another clinical trial within 28 days prior to dosing of study drugs;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Time of the Last Quantifiable Sample (AUC0-last) of Uprifosbuvir | 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 | 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. |
| Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Infinity (AUC0-inf) of Uprifosbuvir | 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 | 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. |
| Area Under the Plasma Drug Concentration-Time Curve From Start of Dosing to 24 Hours Post-Dose (AUC0-24hr) of Uprifosbuvir | Pre-dose (0), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose | 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. |
| Maximum Plasma Drug Concentration (Cmax) of Uprifosbuvir | 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 | 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. |
| Plasma Drug Concentration at 24 Hours (C24hr) of Uprifosbuvir | 24 hours post-dose | 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. |
| Time to Reach Cmax (Tmax) of Uprifosbuvir | 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 | 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. |
| Apparent Terminal Half-Life (t1/2) of Uprifosbuvir | 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 | 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. |
| Apparent Total Clearance From Plasma After Oral Administration (CL/F) of Uprifosbuvir | 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 | 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. |
| Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) of Uprifosbuvir | 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 | 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. |
| AUC0-last of Uprifosbuvir Metabolite M5 | 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 | 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. |
| AUC0-inf of Uprifosbuvir Metabolite M5 | 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 | 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. |
| AUC0-24hr of Uprifosbuvir Metabolite M5 | Pre-dose (0), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose | 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. |
| Cmax of Uprifosbuvir Metabolite M5 | 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 | 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. |
| C24hr of Uprifosbuvir Metabolite M5 | 24 hours post-dose | 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. |
| Lag Time (Tlag) for Uprifosbuvir Metabolite M5 | 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 | 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). |
| Tmax of Uprifosbuvir Metabolite M5 | 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 | 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. |
| Apparent t1/2 of Uprifosbuvir Metabolite M5 | 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 | 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. |
| AUC0-last of Uprifosbuvir Metabolite M6 | 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 | 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. |
| AUC0-inf of Uprifosbuvir Metabolite M6 | 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 | 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. |
| AUC0-24hr of Uprifosbuvir Metabolite M6 | Pre-dose (0), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose | 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. |
| Cmax of Uprifosbuvir Metabolite M6 | 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 | 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. |
| C24hr of Uprifosbuvir Metabolite M6 | 24 hours post-dose | 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. |
| Tmax of Uprifosbuvir Metabolite M6 | 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 | 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. |
| Apparent t1/2 of Uprifosbuvir Metabolite M6 | 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 | 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. |
| AUC0-last of Ruzasvir | 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 | 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. |
| AUC0-inf of Ruzasvir | 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 | 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. |
| AUC0-24hr of Ruzasvir | Pre-dose (0), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose | 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. |
| Maximum Plasma Drug Concentration (Cmax) of Ruzasvir | 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 | 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. |
| C24hr of Ruzasvir | 24 hours post-dose | 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. |
| Tmax of Ruzasvir | 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 | 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. |
| Apparent t1/2 of Ruzasvir | 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 | 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. |
| CL/F of Ruzasvir | 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 | 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. |
| Vz/F of Ruzasvir | 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 | 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. |
Participant flow
Recruitment details
Participants with moderate hepatic insufficiency (HI), severe HI, and healthy controls were recruited at 2 study centers in the United States.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 8 |
| 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. | 8 |
| 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. | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | Moderate HI Participants | Severe HI Participants | Healthy Participants | Total |
|---|---|---|---|---|
| Age, Continuous | 58.3 Years STANDARD_DEVIATION 8.7 | 55.4 Years STANDARD_DEVIATION 8.2 | 57.6 Years STANDARD_DEVIATION 6.3 | 57.1 Years STANDARD_DEVIATION 7.5 |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 5 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 1 / 8 | 3 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Apparent t1/2 of Ruzasvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate HI Participants | Apparent t1/2 of Ruzasvir | 38.08 hr | Geometric Coefficient of Variation 23.1 |
| Severe HI Participants | Apparent t1/2 of Ruzasvir | 47.26 hr | Geometric Coefficient of Variation 36.6 |
| Healthy Participants | Apparent t1/2 of Ruzasvir | 30.43 hr | Geometric Coefficient of Variation 14.6 |
Primary
Apparent t1/2 of Uprifosbuvir Metabolite M5
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate HI Participants | Apparent t1/2 of Uprifosbuvir Metabolite M5 | 24.09 hr | Geometric Coefficient of Variation 17.2 |
| Severe HI Participants | Apparent t1/2 of Uprifosbuvir Metabolite M5 | 25.64 hr | Geometric Coefficient of Variation 19.2 |
| Healthy Participants | Apparent t1/2 of Uprifosbuvir Metabolite M5 | 23.59 hr | Geometric Coefficient of Variation 9.7 |
Primary
Apparent t1/2 of Uprifosbuvir Metabolite M6
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate HI Participants | Apparent t1/2 of Uprifosbuvir Metabolite M6 | 26.96 hr | Geometric Coefficient of Variation 19.4 |
| Severe HI Participants | Apparent t1/2 of Uprifosbuvir Metabolite M6 | 26.45 hr | Geometric Coefficient of Variation 31.3 |
| Healthy Participants | Apparent t1/2 of Uprifosbuvir Metabolite M6 | 33.98 hr | Geometric Coefficient of Variation 37.7 |
Primary
Apparent Terminal Half-Life (t1/2) of Uprifosbuvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate HI Participants | Apparent Terminal Half-Life (t1/2) of Uprifosbuvir | 3.66 hr | Geometric Coefficient of Variation 21.7 |
| Severe HI Participants | Apparent Terminal Half-Life (t1/2) of Uprifosbuvir | 3.56 hr | Geometric Coefficient of Variation 47.5 |
| Healthy Participants | Apparent Terminal Half-Life (t1/2) of Uprifosbuvir | 3.17 hr | Geometric Coefficient of Variation 38.5 |
Primary
Apparent Total Clearance From Plasma After Oral Administration (CL/F) of Uprifosbuvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate HI Participants | Apparent Total Clearance From Plasma After Oral Administration (CL/F) of Uprifosbuvir | 153 L/hr | Geometric Coefficient of Variation 39.9 |
| Severe HI Participants | Apparent Total Clearance From Plasma After Oral Administration (CL/F) of Uprifosbuvir | 102 L/hr | Geometric Coefficient of Variation 61.1 |
| Healthy Participants | Apparent Total Clearance From Plasma After Oral Administration (CL/F) of Uprifosbuvir | 219 L/hr | Geometric Coefficient of Variation 77.6 |
Primary
Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) of Uprifosbuvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate HI Participants | Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) of Uprifosbuvir | 809 L | Geometric Coefficient of Variation 43.8 |
| Severe HI Participants | Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) of Uprifosbuvir | 524 L | Geometric Coefficient of Variation 57 |
| Healthy Participants | Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F) of Uprifosbuvir | 1000 L | Geometric Coefficient of Variation 83 |
Primary
Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Infinity (AUC0-inf) of Uprifosbuvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Infinity (AUC0-inf) of Uprifosbuvir | 5.39 µM*hr |
| Severe HI Participants | Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Infinity (AUC0-inf) of Uprifosbuvir | 8.09 µM*hr |
| Healthy Participants | Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Infinity (AUC0-inf) of Uprifosbuvir | 3.76 µM*hr |
90% CI: [0.88, 2.31]
90% CI: [1.33, 3.48]
Primary
Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Time of the Last Quantifiable Sample (AUC0-last) of Uprifosbuvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | 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 |
| Severe HI Participants | Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Time of the Last Quantifiable Sample (AUC0-last) of Uprifosbuvir | 8.02 µM*hr |
| Healthy Participants | Area Under the Drug Plasma Concentration-Time Curve From Start of Dosing to Time of the Last Quantifiable Sample (AUC0-last) of Uprifosbuvir | 3.74 µM*hr |
90% CI: [0.89, 2.31]
90% CI: [1.33, 3.47]
Primary
Area Under the Plasma Drug Concentration-Time Curve From Start of Dosing to 24 Hours Post-Dose (AUC0-24hr) of Uprifosbuvir
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.
Time frame: Pre-dose (0), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | 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 |
| Severe HI Participants | Area Under the Plasma Drug Concentration-Time Curve From Start of Dosing to 24 Hours Post-Dose (AUC0-24hr) of Uprifosbuvir | 8.02 µM*hr |
| Healthy Participants | Area Under the Plasma Drug Concentration-Time Curve From Start of Dosing to 24 Hours Post-Dose (AUC0-24hr) of Uprifosbuvir | 3.74 µM*hr |
90% CI: [0.89, 2.31]
90% CI: [1.33, 3.47]
Primary
AUC0-24hr of Ruzasvir
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.
Time frame: Pre-dose (0), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | AUC0-24hr of Ruzasvir | 1.04 µM*hr |
| Severe HI Participants | AUC0-24hr of Ruzasvir | 1.05 µM*hr |
| Healthy Participants | AUC0-24hr of Ruzasvir | 1.17 µM*hr |
90% CI: [0.6, 1.33]
90% CI: [0.6, 1.34]
Primary
AUC0-24hr of Uprifosbuvir Metabolite M5
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.
Time frame: Pre-dose (0), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | AUC0-24hr of Uprifosbuvir Metabolite M5 | 2.41 µM*hr |
| Severe HI Participants | AUC0-24hr of Uprifosbuvir Metabolite M5 | 2.28 µM*hr |
| Healthy Participants | AUC0-24hr of Uprifosbuvir Metabolite M5 | 3.12 µM*hr |
90% CI: [0.57, 1.05]
90% CI: [0.54, 0.99]
Primary
AUC0-24hr of Uprifosbuvir Metabolite M6
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.
Time frame: Pre-dose (0), and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | AUC0-24hr of Uprifosbuvir Metabolite M6 | 13.1 µM*hr |
| Severe HI Participants | AUC0-24hr of Uprifosbuvir Metabolite M6 | 13.2 µM*hr |
| Healthy Participants | AUC0-24hr of Uprifosbuvir Metabolite M6 | 16.6 µM*hr |
90% CI: [0.62, 1.01]
90% CI: [0.63, 1.02]
Primary
AUC0-inf of Ruzasvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | AUC0-inf of Ruzasvir | 2.60 µM*hr |
| Severe HI Participants | AUC0-inf of Ruzasvir | 3.32 µM*hr |
| Healthy Participants | AUC0-inf of Ruzasvir | 2.10 µM*hr |
90% CI: [0.91, 1.68]
90% CI: [1.17, 2.14]
Primary
AUC0-inf of Uprifosbuvir Metabolite M5
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | AUC0-inf of Uprifosbuvir Metabolite M5 | 6.78 µM*hr |
| Severe HI Participants | AUC0-inf of Uprifosbuvir Metabolite M5 | 7.22 µM*hr |
| Healthy Participants | AUC0-inf of Uprifosbuvir Metabolite M5 | 8.44 µM*hr |
90% CI: [0.58, 1.11]
90% CI: [0.62, 1.18]
Primary
AUC0-inf of Uprifosbuvir Metabolite M6
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | AUC0-inf of Uprifosbuvir Metabolite M6 | 30.1 µM*hr |
| Severe HI Participants | AUC0-inf of Uprifosbuvir Metabolite M6 | 28.7 µM*hr |
| Healthy Participants | AUC0-inf of Uprifosbuvir Metabolite M6 | 47.0 µM*hr |
90% CI: [0.48, 0.86]
90% CI: [0.46, 0.82]
Primary
AUC0-last of Ruzasvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | AUC0-last of Ruzasvir | 2.30 µM*hr |
| Severe HI Participants | AUC0-last of Ruzasvir | 2.70 µM*hr |
| Healthy Participants | AUC0-last of Ruzasvir | 1.98 µM*hr |
90% CI: [0.85, 1.58]
90% CI: [1, 1.85]
Primary
AUC0-last of Uprifosbuvir Metabolite M5
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | AUC0-last of Uprifosbuvir Metabolite M5 | 6.46 µM*hr |
| Severe HI Participants | AUC0-last of Uprifosbuvir Metabolite M5 | 6.79 µM*hr |
| Healthy Participants | AUC0-last of Uprifosbuvir Metabolite M5 | 8.11 µM*hr |
90% CI: [0.58, 1.1]
90% CI: [0.61, 1.16]
Primary
AUC0-last of Uprifosbuvir Metabolite M6
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | AUC0-last of Uprifosbuvir Metabolite M6 | 28.6 µM*hr |
| Severe HI Participants | AUC0-last of Uprifosbuvir Metabolite M6 | 27.4 µM*hr |
| Healthy Participants | AUC0-last of Uprifosbuvir Metabolite M6 | 41.8 µM*hr |
90% CI: [0.52, 0.9]
90% CI: [0.5, 0.86]
Primary
C24hr of Ruzasvir
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.
Time frame: 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | C24hr of Ruzasvir | 27.6 nM |
| Severe HI Participants | C24hr of Ruzasvir | 32.4 nM |
| Healthy Participants | C24hr of Ruzasvir | 23.0 nM |
90% CI: [0.9, 1.6]
90% CI: [1.06, 1.87]
Primary
C24hr of Uprifosbuvir Metabolite M5
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.
Time frame: 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | C24hr of Uprifosbuvir Metabolite M5 | 124 nM |
| Severe HI Participants | C24hr of Uprifosbuvir Metabolite M5 | 122 nM |
| Healthy Participants | C24hr of Uprifosbuvir Metabolite M5 | 150 nM |
90% CI: [0.6, 1.15]
90% CI: [0.59, 1.13]
Primary
C24hr of Uprifosbuvir Metabolite M6
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.
Time frame: 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | C24hr of Uprifosbuvir Metabolite M6 | 402 nM |
| Severe HI Participants | C24hr of Uprifosbuvir Metabolite M6 | 410 nM |
| Healthy Participants | C24hr of Uprifosbuvir Metabolite M6 | 564 nM |
90% CI: [0.57, 0.89]
90% CI: [0.58, 0.91]
Primary
CL/F of Ruzasvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate HI Participants | CL/F of Ruzasvir | 28.4 L/hr | Geometric Coefficient of Variation 36.7 |
| Severe HI Participants | CL/F of Ruzasvir | 20.6 L/hr | Geometric Coefficient of Variation 52.8 |
| Healthy Participants | CL/F of Ruzasvir | 32.6 L/hr | Geometric Coefficient of Variation 54.6 |
Primary
Cmax of Uprifosbuvir Metabolite M5
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | Cmax of Uprifosbuvir Metabolite M5 | 169 nM |
| Severe HI Participants | Cmax of Uprifosbuvir Metabolite M5 | 151 nM |
| Healthy Participants | Cmax of Uprifosbuvir Metabolite M5 | 203 nM |
90% CI: [0.61, 1.13]
90% CI: [0.55, 1.01]
Primary
Cmax of Uprifosbuvir Metabolite M6
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | Cmax of Uprifosbuvir Metabolite M6 | 851 nM |
| Severe HI Participants | Cmax of Uprifosbuvir Metabolite M6 | 834 nM |
| Healthy Participants | Cmax of Uprifosbuvir Metabolite M6 | 1070 nM |
90% CI: [0.61, 1.05]
90% CI: [0.6, 1.03]
Primary
Lag Time (Tlag) for Uprifosbuvir Metabolite M5
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).
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate HI Participants | Lag Time (Tlag) for Uprifosbuvir Metabolite M5 | 3.00 hr |
| Severe HI Participants | Lag Time (Tlag) for Uprifosbuvir Metabolite M5 | 2.53 hr |
| Healthy Participants | Lag Time (Tlag) for Uprifosbuvir Metabolite M5 | 2.00 hr |
Primary
Maximum Plasma Drug Concentration (Cmax) of Ruzasvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | Maximum Plasma Drug Concentration (Cmax) of Ruzasvir | 105 nM |
| Severe HI Participants | Maximum Plasma Drug Concentration (Cmax) of Ruzasvir | 92.5 nM |
| Healthy Participants | Maximum Plasma Drug Concentration (Cmax) of Ruzasvir | 137 nM |
90% CI: [0.45, 1.3]
90% CI: [0.4, 1.14]
Primary
Maximum Plasma Drug Concentration (Cmax) of Uprifosbuvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Moderate HI Participants | Maximum Plasma Drug Concentration (Cmax) of Uprifosbuvir | 1560 nM |
| Severe HI Participants | Maximum Plasma Drug Concentration (Cmax) of Uprifosbuvir | 2130 nM |
| Healthy Participants | Maximum Plasma Drug Concentration (Cmax) of Uprifosbuvir | 1180 nM |
90% CI: [0.81, 2.15]
90% CI: [1.11, 2.94]
Primary
Plasma Drug Concentration at 24 Hours (C24hr) of Uprifosbuvir
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.
Time frame: 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate HI Participants | Plasma Drug Concentration at 24 Hours (C24hr) of Uprifosbuvir | 7.01 nM |
| Severe HI Participants | Plasma Drug Concentration at 24 Hours (C24hr) of Uprifosbuvir | 8.56 nM |
| Healthy Participants | Plasma Drug Concentration at 24 Hours (C24hr) of Uprifosbuvir | 2.55 nM |
Primary
Time to Reach Cmax (Tmax) of Uprifosbuvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate HI Participants | Time to Reach Cmax (Tmax) of Uprifosbuvir | 1.00 hr |
| Severe HI Participants | Time to Reach Cmax (Tmax) of Uprifosbuvir | 0.50 hr |
| Healthy Participants | Time to Reach Cmax (Tmax) of Uprifosbuvir | 1.25 hr |
Primary
Tmax of Ruzasvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate HI Participants | Tmax of Ruzasvir | 3.00 hr |
| Severe HI Participants | Tmax of Ruzasvir | 2.03 hr |
| Healthy Participants | Tmax of Ruzasvir | 3.00 hr |
Primary
Tmax of Uprifosbuvir Metabolite M5
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate HI Participants | Tmax of Uprifosbuvir Metabolite M5 | 14.00 hr |
| Severe HI Participants | Tmax of Uprifosbuvir Metabolite M5 | 16.00 hr |
| Healthy Participants | Tmax of Uprifosbuvir Metabolite M5 | 15.00 hr |
Primary
Tmax of Uprifosbuvir Metabolite M6
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate HI Participants | Tmax of Uprifosbuvir Metabolite M6 | 6.00 hr |
| Severe HI Participants | Tmax of Uprifosbuvir Metabolite M6 | 4.00 hr |
| Healthy Participants | Tmax of Uprifosbuvir Metabolite M6 | 4.00 hr |
Primary
Vz/F of Ruzasvir
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.
Time frame: 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
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate HI Participants | Vz/F of Ruzasvir | 1560 L | Geometric Coefficient of Variation 49.8 |
| Severe HI Participants | Vz/F of Ruzasvir | 1400 L | Geometric Coefficient of Variation 37.9 |
| Healthy Participants | Vz/F of Ruzasvir | 1430 L | Geometric Coefficient of Variation 48.1 |