Hepatitis C
Conditions
Brief summary
The purpose of this study is to compare the plasma pharmacokinetics (PK) of single doses of MK-3682B, a fixed dose combination (FDC) tablet containing uprifosbuvir (MK-3682) + grazoprevir (MK-5172) + ruzasvir (MK-8408) in participants with moderate (Part 1) and severe (Part 2) renal insufficiency (RI) to plasma PK in healthy participants.
Interventions
DRUGMK-3682B
FDC oral tablet containing 225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir.
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
All Participants: * Healthy adult males or females 18-80 years of age at screening * Continuous non-smokers or moderate smokers (≤ 20 cigarettes/day or the equivalent) and agrees to consume no more than 10 cigarettes per day during the study period * BMI ≥ 18 and ≤ 40.0 kg/m\^2 * Agrees not to become pregnant or father a child during participation in the study * Females of childbearing potential must either be abstinent for 14 days prior to dosing and throughout the study or be using an acceptable birth control method * Vasectomized or non-vasectomized males must agree to use a condom with spermicide or abstain from sexual intercourse from the first dose until 90 days after dosing * Males must agree not to donate sperm from dosing until 90 days after dosing Moderate and Severe RI Participants: * Baseline health is judged to be stable based on medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the Investigator * Has had no clinically significant change in renal status at least 1 month prior to dosing and is not currently or has not previously been on hemodialysis * Moderate RI: has baseline eGFR ≥ 30 mL/min/1.73m\^2 and \< 60 mL/min/1.73m\^2, based on the Modification of Diet in Renal Disease (MDRD) equation at screening * Severe RI: has baseline eGFR ≥ 15 mL/min/1.73m\^2 and \< 30 mL/min/1.73m\^2, based on the MDRD equation at screening Healthy Participants: * Is within ± 10 years of the mean age of moderate and severe RI arms * BMI is within 10% of the mean BMI of participants with moderate and severe RI arms * Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the Investigator * Baseline CLcr ≥ 80 mL/min based on Cockcroft-Gault equation at screening
Exclusion criteria
* Is mentally or legally incapacitated or has significant emotional problems at the time of the screening * History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the Investigator * History of any illness that, in the opinion of the Investigator, might confound the results of the study or poses an additional risk by participating in the study * Is female and pregnant or lactating * Positive results for the urine or saliva drug screen or urine or breath alcohol screen at screening or check-in unless the positive drug screen is due to prescription drug use that is approved by the Investigator and Sponsor * Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) * Seated heart rate is equal to or lower than 44 beats per minute (bpm) or higher than 100 bpm at screening * Has had a renal transplant or has had nephrectomy * Donation of blood or had significant blood loss within 56 days prior to dosing of study drug, or donation of plasma within 7 days prior to dosing * Has participated in another clinical trial within 28 days prior to dosing of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-24 of Uprifosbuvir Metabolite M5 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose | AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from dosing to 24 hours following oral administration of MK-3682B. |
| Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682) | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-last is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to the time of the last quantifiable (\< lower limit of quantification \[LLOQ\]) sample following oral administration of MK-3682B. |
| AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-∞ is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to infinity following oral administration of MK-3682B. |
| AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose | AUC0-24 is a measure of total exposure to uprifosbuvir in plasma from dosing to 24 hours following oral administration of MK-3682B. |
| Maximum Plasma Concentration (Cmax) of Uprifosbuvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Cmax is the maximum amount of uprifosbuvir in plasma following oral administration of MK-3682B. |
| Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir | 24 hours post-dose | C24 is the plasma concentration of uprifosbuvir 24 hours following oral administration of MK-3682B. |
| Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir following oral administration of MK-3682B. |
| Apparent Total Body Clearance (CL/F) of Uprifosbuvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | CL/F is the apparent total body clearance of uprifosbuvir following oral administration of MK-3682B. |
| Apparent Volume of Distribution (Vz/F) of Uprifosbuvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Vz/F is the apparent volume of distribution of uprifosbuvir following oral administration of MK-3682B. |
| Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | t1/2 is the amount of time required to clear 50% of uprifosbuvir from plasma following oral administration of MK-3682B. |
| AUC0-last of Uprifosbuvir Metabolite M5 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-last is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B. |
| AUC0-∞ of Uprifosbuvir Metabolite M5 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to infinity following oral administration of MK-3682B. |
| Cmax of Uprifosbuvir Metabolite M5 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Cmax is the maximum amount of uprifosbuvir metabolite M5 in plasma following oral administration of MK-3682B. |
| C24 of Uprifosbuvir Metabolite M5 | 24 hours post-dose | C24 is the plasma concentration of uprifosbuvir metabolite M5 24 hours following oral administration of MK-3682B. |
| Tmax of Uprifosbuvir Metabolite M5 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M5 following oral administration of MK-3682B. |
| Lag Time (Tlag) of Uprifosbuvir Metabolite M5 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Tlag is the time from dosing to first appearance in plasma of uprifosbuvir metabolite M5 following oral administration of MK-3682B. |
| t½ of Uprifosbuvir Metabolite M5 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M5 from plasma following oral administration of MK-3682B. |
| AUC0-last of Uprifosbuvir Metabolite M6 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-last is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B. |
| AUC0-∞ of Uprifosbuvir Metabolite M6 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to infinity following oral administration of MK-3682B. |
| AUC0-24 of Uprifosbuvir Metabolite M6 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose | AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from dosing to 24 hours following oral administration of MK-3682B. |
| Cmax of Uprifosbuvir Metabolite M6 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Cmax is the maximum amount of uprifosbuvir metabolite M6 in plasma following oral administration of MK-3682B. |
| C24 of Uprifosbuvir Metabolite M6 | 24 hours post-dose | C24 is the plasma concentration of uprifosbuvir metabolite M6 24 hours following oral administration of MK-3682B. |
| Tmax of Uprifosbuvir Metabolite M6 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M6 following oral administration of MK-3682B. |
| t½ of Uprifosbuvir Metabolite M6 | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M6 from plasma following oral administration of MK-3682B. |
| AUC0-last of Grazoprevir (MK-5172) | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-last is a measure of total exposure to grazoprevir in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B. |
| AUC0-∞ of Grazoprevir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-∞ is a measure of total exposure to grazoprevir in plasma from the start of dosing to infinity following oral administration of MK-3682B. |
| AUC0-24 of Grazoprevir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose | AUC0-24 is a measure of total exposure to grazoprevir in plasma from the start of dosing to 24 hours post-dose following oral administration of MK-3682B. |
| Cmax of Grazoprevir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Cmax is the maximum amount of grazoprevir in plasma following oral administration of MK-3682B. |
| C24 of Grazoprevir | 24 hours post-dose | C24 is the plasma concentration of grazoprevir 24 hours following oral administration of MK-3682B. |
| Tmax of Grazoprevir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Tmax is the time required to reach the maximum post-dose plasma concentration of grazoprevir following oral administration of MK-3682B. |
| CL/F of Grazoprevir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | CL/F is the apparent total body clearance of grazoprevir following oral administration of MK-3682B. |
| Vz/F of Grazoprevir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Vz/F is the apparent volume of distribution of grazoprevir following oral administration of MK-3682B. |
| t½ of Grazoprevir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | t1/2 is the amount of time required to clear 50% of grazoprevir from plasma following oral administration of MK-3682B. |
| AUC0-last of Ruzasvir (MK-8408) | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-last is a measure of total exposure to ruzasvir in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B. |
| AUC0-∞ of Ruzasvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | AUC0-∞ is a measure of total exposure to ruzasvir in plasma from the start of dosing to infinity following oral administration of MK-3682B. |
| AUC0-24 of Ruzasvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose | AUC0-24 is a measure of total exposure to ruzasvir in plasma from dosing to 24 hours following oral administration of MK-3682B. |
| Cmax of Ruzasvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Cmax is the maximum amount of ruzasvir in plasma following oral administration of MK-3682B. |
| C24 of Ruzasvir | 24 hours post-dose | C24 is the plasma concentration of ruzasvir 24 hours following oral administration of MK-3682B. |
| Tmax of Ruzasvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Tmax is the time required to reach the maximum post-dose plasma concentration of ruzasvir following oral administration of MK-3682B. |
| CL/F of Ruzasvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | CL/F is the apparent total body clearance of ruzasvir following oral administration of MK-3682B. |
| Vz/F of Ruzasvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | Vz/F is the apparent volume of distribution of ruzasvir following oral administration of MK-3682B. |
| t½ of Ruzasvir | 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose | t1/2 is the amount of time required to clear 50% of ruzasvir from plasma following oral administration of MK-3682B. |
Participant flow
Recruitment details
In Part 1, adults with moderate renal impairment (RI; determined by estimated glomerular filtration rate \[eGFR\]), and healthy participants, were recruited at 2 sites in the US. Part 2 was intended to enroll severe RI participants but was not conducted based on results of a planned interim analysis of Part 1 data.
Participants by arm
| Arm | Count |
|---|---|
| Moderate RI Participants Participants with an eGFR of ≥30 mL/min/1.73m\^2 to \<60 mL/min/1.73m\^2 took 2 MK-3682B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours. | 8 |
| Healthy Participants Healthy participants (CLcr ≥80 mL/min) took 2 MK-362B FDC tablets (225 mg uprifosbuvir + 50 mg grazoprevir + 30 mg ruzasvir per tablet) on Day 1 after fasting for 10 hours. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Moderate RI Participants | Healthy Participants | Total |
|---|---|---|---|
| Age, Continuous | 69.6 Years STANDARD_DEVIATION 9 | 65.8 Years STANDARD_DEVIATION 2.6 | 67.7 Years STANDARD_DEVIATION 6.7 |
| Body Mass Index (BMI) | 30.32 kg/m^2 STANDARD_DEVIATION 4.023 | 30.11 kg/m^2 STANDARD_DEVIATION 2.057 | 30.22 kg/m^2 STANDARD_DEVIATION 3.088 |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 2 / 8 | 1 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir
t1/2 is the amount of time required to clear 50% of uprifosbuvir from plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir | 2.09 Hours | Geometric Coefficient of Variation 65.6 |
| Healthy Participants | Apparent Terminal Half-life in Plasma (t½) of Uprifosbuvir | 2.60 Hours | Geometric Coefficient of Variation 92.9 |
Primary
Apparent Total Body Clearance (CL/F) of Uprifosbuvir
CL/F is the apparent total body clearance of uprifosbuvir following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | Apparent Total Body Clearance (CL/F) of Uprifosbuvir | 96.3 Liters/hour | Geometric Coefficient of Variation 51.5 |
| Healthy Participants | Apparent Total Body Clearance (CL/F) of Uprifosbuvir | 193 Liters/hour | Geometric Coefficient of Variation 34.7 |
Primary
Apparent Volume of Distribution (Vz/F) of Uprifosbuvir
Vz/F is the apparent volume of distribution of uprifosbuvir following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | Apparent Volume of Distribution (Vz/F) of Uprifosbuvir | 290 Liters | Geometric Coefficient of Variation 51.7 |
| Healthy Participants | Apparent Volume of Distribution (Vz/F) of Uprifosbuvir | 724 Liters | Geometric Coefficient of Variation 115.2 |
Primary
Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682)
AUC0-last is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to the time of the last quantifiable (\< lower limit of quantification \[LLOQ\]) sample following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682) | 8.55 uM*hr |
| Healthy Participants | Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Time of Last Measurable Concentration (AUC0-last) of Uprifosbuvir (MK-3682) | 4.23 uM*hr |
90% CI: [1.4, 2.92]
Primary
AUC0-24 of Grazoprevir
AUC0-24 is a measure of total exposure to grazoprevir in plasma from the start of dosing to 24 hours post-dose following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 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_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-24 of Grazoprevir | 0.436 uM*hr |
| Healthy Participants | AUC0-24 of Grazoprevir | 0.380 uM*hr |
90% CI: [0.51, 2.57]
Primary
AUC0-24 of Ruzasvir
AUC0-24 is a measure of total exposure to ruzasvir in plasma from dosing to 24 hours following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 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_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-24 of Ruzasvir | 1.11 uM*hr |
| Healthy Participants | AUC0-24 of Ruzasvir | 0.744 uM*hr |
90% CI: [1.13, 1.98]
Primary
AUC0-24 of Uprifosbuvir Metabolite M5
AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from dosing to 24 hours following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 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_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-24 of Uprifosbuvir Metabolite M5 | 4.59 uM*hr |
| Healthy Participants | AUC0-24 of Uprifosbuvir Metabolite M5 | 2.67 uM*hr |
90% CI: [1.15, 2.56]
Primary
AUC0-24 of Uprifosbuvir Metabolite M6
AUC0-24 is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from dosing to 24 hours following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 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_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-24 of Uprifosbuvir Metabolite M6 | 27.2 uM*hr |
| Healthy Participants | AUC0-24 of Uprifosbuvir Metabolite M6 | 13.9 uM*hr |
90% CI: [1.54, 2.48]
Primary
AUC0-last of Grazoprevir (MK-5172)
AUC0-last is a measure of total exposure to grazoprevir in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-last of Grazoprevir (MK-5172) | 0.974 uM*hr |
| Healthy Participants | AUC0-last of Grazoprevir (MK-5172) | 0.730 uM*hr |
90% CI: [0.65, 2.75]
Primary
AUC0-last of Ruzasvir (MK-8408)
AUC0-last is a measure of total exposure to ruzasvir in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-last of Ruzasvir (MK-8408) | 2.07 uM*hr |
| Healthy Participants | AUC0-last of Ruzasvir (MK-8408) | 1.32 uM*hr |
90% CI: [1.19, 2.05]
Primary
AUC0-last of Uprifosbuvir Metabolite M5
AUC0-last is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-last of Uprifosbuvir Metabolite M5 | 14.8 uM*hr |
| Healthy Participants | AUC0-last of Uprifosbuvir Metabolite M5 | 7.62 uM*hr |
90% CI: [1.39, 2.72]
Primary
AUC0-last of Uprifosbuvir Metabolite M6
AUC0-last is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to the time of the last quantifiable (\<LLOQ) sample following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-last of Uprifosbuvir Metabolite M6 | 63.9 uM*hr |
| Healthy Participants | AUC0-last of Uprifosbuvir Metabolite M6 | 33.5 uM*hr |
90% CI: [1.44, 2.53]
Primary
AUC0-∞ of Grazoprevir
AUC0-∞ is a measure of total exposure to grazoprevir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants except 1 are included in the analysis. One participant in the Moderate RI group did not have a well characterized terminal phase and their value was set to missing.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-∞ of Grazoprevir | 1.32 uM*hr |
| Healthy Participants | AUC0-∞ of Grazoprevir | 0.826 uM*hr |
90% CI: [0.79, 3.19]
Primary
AUC0-∞ of Ruzasvir
AUC0-∞ is a measure of total exposure to ruzasvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-∞ of Ruzasvir | 2.19 uM*hr |
| Healthy Participants | AUC0-∞ of Ruzasvir | 1.40 uM*hr |
90% CI: [1.2, 2.05]
Primary
AUC0-∞ of Uprifosbuvir Metabolite M5
AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M5 in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-∞ of Uprifosbuvir Metabolite M5 | 16.2 uM*hr |
| Healthy Participants | AUC0-∞ of Uprifosbuvir Metabolite M5 | 7.99 uM*hr |
90% CI: [1.5, 2.74]
Primary
AUC0-∞ of Uprifosbuvir Metabolite M6
AUC0-∞ is a measure of total exposure to uprifosbuvir metabolite M6 in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC0-∞ of Uprifosbuvir Metabolite M6 | 71.4 uM*hr |
| Healthy Participants | AUC0-∞ of Uprifosbuvir Metabolite M6 | 36.2 uM*hr |
90% CI: [1.48, 2.63]
Primary
AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir
AUC0-24 is a measure of total exposure to uprifosbuvir in plasma from dosing to 24 hours following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 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_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir | 8.54 uM*hr |
| Healthy Participants | AUC From Dosing to 24 Hours Post-dose (AUC0-24) of Uprifosbuvir | 4.24 uM*hr |
90% CI: [1.39, 2.92]
Primary
AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir
AUC0-∞ is a measure of total exposure to uprifosbuvir in plasma from the start of dosing to infinity following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir | 8.56 uM*hr |
| Healthy Participants | AUC From Dosing to Infinity (AUC0-∞) of Uprifosbuvir | 4.28 uM*hr |
90% CI: [1.39, 2.89]
Primary
C24 of Grazoprevir
C24 is the plasma concentration of grazoprevir 24 hours following oral administration of MK-3682B.
Time frame: 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | C24 of Grazoprevir | 9.41 nM |
| Healthy Participants | C24 of Grazoprevir | 7.36 nM |
90% CI: [0.56, 2.91]
Primary
C24 of Ruzasvir
C24 is the plasma concentration of ruzasvir 24 hours following oral administration of MK-3682B.
Time frame: 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | C24 of Ruzasvir | 23.9 nM |
| Healthy Participants | C24 of Ruzasvir | 15.5 nM |
90% CI: [1.15, 2.07]
Primary
C24 of Uprifosbuvir Metabolite M5
C24 is the plasma concentration of uprifosbuvir metabolite M5 24 hours following oral administration of MK-3682B.
Time frame: 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | C24 of Uprifosbuvir Metabolite M5 | 262 nM |
| Healthy Participants | C24 of Uprifosbuvir Metabolite M5 | 129 nM |
90% CI: [1.38, 2.97]
Primary
C24 of Uprifosbuvir Metabolite M6
C24 is the plasma concentration of uprifosbuvir metabolite M6 24 hours following oral administration of MK-3682B.
Time frame: 24 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | C24 of Uprifosbuvir Metabolite M6 | 905 nM |
| Healthy Participants | C24 of Uprifosbuvir Metabolite M6 | 466 nM |
90% CI: [1.47, 2.57]
Primary
CL/F of Grazoprevir
CL/F is the apparent total body clearance of grazoprevir following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants except 1 are included in the analysis. One participant in the Moderate RI group did not have a well characterized terminal phase and their value was set to missing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | CL/F of Grazoprevir | 99.1 Liters/hour | Geometric Coefficient of Variation 122 |
| Healthy Participants | CL/F of Grazoprevir | 158 Liters/hour | Geometric Coefficient of Variation 57.9 |
Primary
CL/F of Ruzasvir
CL/F is the apparent total body clearance of ruzasvir following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | CL/F of Ruzasvir | 31.0 Liters/hour | Geometric Coefficient of Variation 34.5 |
| Healthy Participants | CL/F of Ruzasvir | 48.8 Liters/hour | Geometric Coefficient of Variation 31.2 |
Primary
Cmax of Grazoprevir
Cmax is the maximum amount of grazoprevir in plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | Cmax of Grazoprevir | 67.5 nM |
| Healthy Participants | Cmax of Grazoprevir | 54.7 nM |
90% CI: [0.5, 3.05]
Primary
Cmax of Ruzasvir
Cmax is the maximum amount of ruzasvir in plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | Cmax of Ruzasvir | 117 nM |
| Healthy Participants | Cmax of Ruzasvir | 80.9 nM |
90% CI: [1.05, 1.98]
Primary
Cmax of Uprifosbuvir Metabolite M5
Cmax is the maximum amount of uprifosbuvir metabolite M5 in plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | Cmax of Uprifosbuvir Metabolite M5 | 321 nM |
| Healthy Participants | Cmax of Uprifosbuvir Metabolite M5 | 173 nM |
90% CI: [1.2, 2.87]
Primary
Cmax of Uprifosbuvir Metabolite M6
Cmax is the maximum amount of uprifosbuvir metabolite M6 in plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | Cmax of Uprifosbuvir Metabolite M6 | 1540 nM |
| Healthy Participants | Cmax of Uprifosbuvir Metabolite M6 | 906 nM |
90% CI: [1.29, 2.24]
Primary
Lag Time (Tlag) of Uprifosbuvir Metabolite M5
Tlag is the time from dosing to first appearance in plasma of uprifosbuvir metabolite M5 following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate RI Participants | Lag Time (Tlag) of Uprifosbuvir Metabolite M5 | 2.00 Hours |
| Healthy Participants | Lag Time (Tlag) of Uprifosbuvir Metabolite M5 | 2.00 Hours |
Primary
Maximum Plasma Concentration (Cmax) of Uprifosbuvir
Cmax is the maximum amount of uprifosbuvir in plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Moderate RI Participants | Maximum Plasma Concentration (Cmax) of Uprifosbuvir | 3030 nM |
| Healthy Participants | Maximum Plasma Concentration (Cmax) of Uprifosbuvir | 1570 nM |
90% CI: [1.35, 2.74]
Primary
Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir
C24 is the plasma concentration of uprifosbuvir 24 hours following oral administration of MK-3682B.
Time frame: 24 hours post-dose
Population: All Healthy Control participants are included in the analysis. Since \>50% of participants in the Moderate RI group had C24 values \<LLOQ, no data are presented for this group as per Merck policy.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Participants | Plasma Concentration 24 Hours Post-dose (C24) of Uprifosbuvir | 3.65 nM |
Primary
t½ of Grazoprevir
t1/2 is the amount of time required to clear 50% of grazoprevir from plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants except 1 are included in the analysis. One participant in the Moderate RI group did not have a well characterized terminal phase and their value was set to missing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | t½ of Grazoprevir | 42.21 Hours | Geometric Coefficient of Variation 40.3 |
| Healthy Participants | t½ of Grazoprevir | 42.85 Hours | Geometric Coefficient of Variation 26.4 |
Primary
t½ of Ruzasvir
t1/2 is the amount of time required to clear 50% of ruzasvir from plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | t½ of Ruzasvir | 31.50 Hours | Geometric Coefficient of Variation 11.4 |
| Healthy Participants | t½ of Ruzasvir | 29.31 Hours | Geometric Coefficient of Variation 7 |
Primary
t½ of Uprifosbuvir Metabolite M5
t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M5 from plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | t½ of Uprifosbuvir Metabolite M5 | 26.27 Hours | Geometric Coefficient of Variation 45 |
| Healthy Participants | t½ of Uprifosbuvir Metabolite M5 | 25.33 Hours | Geometric Coefficient of Variation 6.4 |
Primary
t½ of Uprifosbuvir Metabolite M6
t1/2 is the amount of time required to clear 50% of uprifosbuvir metabolite M6 from plasma following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | t½ of Uprifosbuvir Metabolite M6 | 33.58 Hours | Geometric Coefficient of Variation 39.7 |
| Healthy Participants | t½ of Uprifosbuvir Metabolite M6 | 30.55 Hours | Geometric Coefficient of Variation 19.7 |
Primary
Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir
Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate RI Participants | Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir | 1.00 Hours |
| Healthy Participants | Time to Reach Maximum Plasma Concentration (Tmax) of Uprifosbuvir | 1.00 Hours |
Primary
Tmax of Grazoprevir
Tmax is the time required to reach the maximum post-dose plasma concentration of grazoprevir following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate RI Participants | Tmax of Grazoprevir | 2.00 Hours |
| Healthy Participants | Tmax of Grazoprevir | 2.25 Hours |
Primary
Tmax of Ruzasvir
Tmax is the time required to reach the maximum post-dose plasma concentration of ruzasvir following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate RI Participants | Tmax of Ruzasvir | 3.00 Hours |
| Healthy Participants | Tmax of Ruzasvir | 3.00 Hours |
Primary
Tmax of Uprifosbuvir Metabolite M5
Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M5 following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate RI Participants | Tmax of Uprifosbuvir Metabolite M5 | 20.00 Hours |
| Healthy Participants | Tmax of Uprifosbuvir Metabolite M5 | 13.00 Hours |
Primary
Tmax of Uprifosbuvir Metabolite M6
Tmax is the time required to reach the maximum post-dose plasma concentration of uprifosbuvir metabolite M6 following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Moderate RI Participants | Tmax of Uprifosbuvir Metabolite M6 | 8.00 Hours |
| Healthy Participants | Tmax of Uprifosbuvir Metabolite M6 | 3.50 Hours |
Primary
Vz/F of Grazoprevir
Vz/F is the apparent volume of distribution of grazoprevir following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants except 1 are included in the analysis. One participant in the Moderate RI group did not have a well characterized terminal phase and their value was set to missing.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | Vz/F of Grazoprevir | 6030 Liters | Geometric Coefficient of Variation 183.5 |
| Healthy Participants | Vz/F of Grazoprevir | 9750 Liters | Geometric Coefficient of Variation 77.5 |
Primary
Vz/F of Ruzasvir
Vz/F is the apparent volume of distribution of ruzasvir following oral administration of MK-3682B.
Time frame: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 48, 72, 96, and 120 hours post-dose
Population: All participants are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Moderate RI Participants | Vz/F of Ruzasvir | 1410 Liters | Geometric Coefficient of Variation 40 |
| Healthy Participants | Vz/F of Ruzasvir | 2060 Liters | Geometric Coefficient of Variation 26.9 |