Chronic Hepatitis C
Conditions
Keywords
Hepatitis C virus, HCV
Brief summary
This is a multi-part study to evaluate the safety, tolerability, and pharmacokinetics (PK) of uprifosbuvir (MK-3682/IDX21437) in healthy participants and in participants infected with Hepatitis C virus (HCV) genotype (GT)1-GT6. The effect of food on the PK of uprifosbuvir will be evaluated. The antiviral activity of uprifosbuvir will also be assessed in HCV-infected participants.
Interventions
DRUGUprifosbuvir
Uprifosbuvir 5 mg, 25 mg, or 50 mg capsule, or 150 mg tablet, administered by mouth.
DRUGPlacebo
Matching placebo to uprifosbuvir capsule administered by mouth.
DRUGItraconazole
Itraconazole is supplied as 10 mg/mL oral solution or 100 mg capsules administered by mouth.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
All Participants: * of childbearing potential must have agreed to use a double method of birth control (one of which must be a barrier) from Screening through at least 90 days after the last dose of the study drug * must not have consumed grapefruit or grapefruit juice within 7 days of Day -1 and throughout the study HCV Participants: * documented clinical history compatible with chronic hepatitis C. * have not received direct-acting antiviral treatment for hepatitis C infection * has HCV Genotype 1, 2, 3, 4, 5 or 6
Exclusion criteria
All Participants: * pregnant or breastfeeding * co-infected with hepatitis B virus (HBV) and/or human immunodeficiency virus (HIV). * decompensated liver disease * other clinically significant medical conditions or laboratory abnormalities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | Up to 42 days | An SAE was defined as any untoward medical occurrence that at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. The percentage of participants who experienced at least one SAE is presented. |
| Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | Up to 42 days | An AE was defined as any untoward medical occurrence in a participant administered study drug, and that does not necessarily have a causal relationship with the study drug(s). An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug(s), whether or not related to study drug(s). The percentage of participants who experienced at least one AE is presented. |
| Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | Up to 13 days | A DLT was defined as any of the following events: Any SAE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 clinical AE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 confirmed laboratory abnormalities considered by the investigator to be at least reasonably or possibly related to study drug, except for asymptomatic Grade ¾ cholesterol and triglyceride; Any clinical or laboratory AE of any intensity that is considered by the investigator to be at least reasonably or possibly related to study drug that necessitates permanent discontinuation of study drug; Confirmed increase in QT interval corrected for heart rate using Fridericia's (QTcF) formula ≥60 msec over Baseline or an absolute QTcF ≥500 msec. |
| Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Up to 42 days | Laboratory abnormalities were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Treatment-emergent AEs (TEAEs)were graded as: Grade 1: Mild TEAE as Worst Severity; Grade 2: Moderate TEAE as Worst Severity; Grade 3: Severe TEAE as Worst Severity; Grade 4: Potentially Life-Threatening TEAE as Worst Severity; Grade 5: TEAE Leading to Death. The percentage of participants who experienced at least one Grade 1, 2, 3, 4 or 5 laboratory abnormality is presented. |
| Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | Up to 14 days | The percentage of participants who discontinued study drug due to an AE is presented. |
| Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. All participants were fasted. |
| AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. |
| AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. |
| AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. |
| AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. |
| AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. |
| AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. |
| AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. |
| AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. |
| Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. All participants were fasted. |
| Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. All participants were fasted. |
| Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. All participants were fasted. |
| Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of Uprifosbuvir After Singe Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. |
| t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted. |
| t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Area under the drug concentration-time curve from time zero to infinity for M6, a metabolite of uprifosbuvir, estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. All participants were fasted. |
| AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. |
| AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. |
| AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. |
| AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. |
| AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. |
| AUC0-inf of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. |
| AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. |
| AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. |
| Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. All participants were fasted. |
| Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Maximum observed plasma drug concentration was obtained. |
| Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. All participants were fasted. |
| Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1,HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Time to maximum plasma concentration was obtained. |
| t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted. |
| t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. |
| Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Cumulative urine excretion of unchanged MK-3682 in healthy participants was obtained. All participants were fasted. |
| Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose | Cumulative urine excretion of unchanged M6 in healthy participants was obtained. All participants were fasted. |
| Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Baseline and Day 8 | Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-infected participants was obtained. |
| Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Baseline and 28 days after last dose of study drug (Up to 42 days) | Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype (Gt) 1, HCV-infected participants was obtained. |
Participant flow
Recruitment details
Per protocol, the Group D part of the study allowed to randomize Genotype 2, 3, 4, 5 and 6 Hepatitis C Virus (HCV)-infected participants, however, only Genotype 2 and 3 HCV-infected participants were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) Participants were administered a single dose of uprifosbuvir-matching placebo as oral capsules under fasted conditions (Cohorts 1a, 2a, 3a, 5a); Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules on Days 1 and 7 in a 2-period crossover design (fasted/fed) with a 6 day washout between dosing periods (Cohort 4a). | 10 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions. | 6 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions. | 6 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) Participants were administered single doses of uprifosbuvir 150 mg as oral capsules on Days 1 and 7 in a 2-period crossover design (fasted/fed) with a 6 day washout between dosing periods. | 6 |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions. | 6 |
| Group A: Placebo (Cohort 6a) Participants were administered single doses of uprifosbuvir-matching placebo oral capsules once daily for 7 days under fasted conditions. | 2 |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions. | 6 |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) Participants were administered a single dose of uprifosbuvir 10 mg as oral capsules under fasted conditions. | 3 |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) Participants were administered a single dose of uprifosbuvir 25 mg as oral capsules under fasted conditions. | 3 |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions. | 3 |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions. | 3 |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) Participants were administered a single dose of uprifosbuvir 300 mg as oral capsules under fasted conditions. | 3 |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) Participants were administered single doses of uprifosbuvir 50 mg as oral capsules once daily for 7 days under fasted conditions. | 11 |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) Participants were administered single doses of uprifosbuvir 150 mg as oral capsules once daily for 7 days under fasted conditions. | 10 |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) Participants were administered single doses of uprifosbuvir 250 mg as oral capsules once daily for 7 days under fasted conditions. | 8 |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions. | 18 |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) Participants were administered single doses of uprifosbuvir 400 mg as oral capsules once daily for 7 days under fasted conditions. | 8 |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. | 8 |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions. | 8 |
| Groups C & D: Placebo (Pooled) Participants were administered single doses of uprifosbuvir-matching placebo as oral capsules once daily for 7 days under fasted conditions. | 9 |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) Participants were administered a single dose of uprifosbuvir 150 mg as oral capsules under fasted conditions. | 3 |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) Participants were administered single doses of uprifosbuvir 300 mg as oral capsules once daily for 7 days under fasted conditions. | 3 |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) Participants were administered single doses of uprifosbuvir 450 mg as oral tablets once daily for 7 days under fasted conditions. | 8 |
| Group F: Uprifosbuvir 300 mg (Tablet) Participants were administered single doses of uprifosbuvir 300 mg as oral tablets once daily for 7 days under fasted conditions. Participants were also administered itraconazole 200 mg twice daily as oral solution on Day -5 and 200 mg once daily from Day -4 to Day 11. | 8 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) Participants were administered a single dose of uprifosbuvir 50 mg as oral capsules under fasted conditions. | 6 |
| Total | 165 |
Baseline characteristics
| Characteristic | Groups C & D: Uprifosbuvir 300 mg (Capsule) | Groups C & D: Uprifosbuvir 400 mg (Capsule) | Groups C & D: Uprifosbuvir 300 mg (Tablet) | Groups C & D: Uprifosbuvir 450 mg (Tablet) | Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Group A: Uprifosbuvir 10 mg (Cohort 1a) | Group A: Uprifosbuvir 25 mg (Cohort 2a) | Group A: Uprifosbuvir 150 mg (Cohort 4a) | Group A: Uprifosbuvir 300 mg (Cohort 5a) | Group A: Placebo (Cohort 6a) | Group A: Uprifosbuvir 300 mg (Cohort 6a) | Group B: Uprifosbuvir 10 mg (Cohort 1b) | Group B: Uprifosbuvir 25 mg (Cohort 2b) | Group B: Uprifosbuvir 50 mg (Cohort 3b) | Group B: Uprifosbuvir 150 mg (Cohort 4b) | Group B: Uprifosbuvir 300 mg (Cohort 5b) | Groups C & D: Uprifosbuvir 50 mg (Capsule) | Groups C & D: Uprifosbuvir 150 mg (Capsule) | Groups C & D: Uprifosbuvir 250 mg (Capsule) | Groups C & D: Placebo (Pooled) | Group E: Uprifosbuvir 150 mg (Cohort 1e) | Group E: Uprifosbuvir 300 mg (Cohort 2e) | Group E: Uprifosbuvir 450 mg (Cohort 3e) | Group F: Uprifosbuvir 300 mg (Tablet) | Group A: Uprifosbuvir 50 mg (Cohort 3a) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 8 Participants | 8 Participants | 8 Participants | 10 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 2 Participants | 6 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 11 Participants | 10 Participants | 8 Participants | 9 Participants | 3 Participants | 3 Participants | 8 Participants | 8 Participants | 6 Participants | 165 Participants |
| Age, Continuous | 40.1 Years STANDARD_DEVIATION 11.69 | 43.3 Years STANDARD_DEVIATION 8.45 | 40.5 Years STANDARD_DEVIATION 11.7 | 40.5 Years STANDARD_DEVIATION 8.94 | 35.3 Years STANDARD_DEVIATION 7.72 | 29.2 Years STANDARD_DEVIATION 7.36 | 33.3 Years STANDARD_DEVIATION 15.06 | 35.5 Years STANDARD_DEVIATION 11.76 | 35.2 Years STANDARD_DEVIATION 9.87 | 36.0 Years STANDARD_DEVIATION 2.83 | 35.3 Years STANDARD_DEVIATION 12.69 | 37.0 Years STANDARD_DEVIATION 9.54 | 42.3 Years STANDARD_DEVIATION 7.23 | 46.7 Years STANDARD_DEVIATION 4.16 | 43.3 Years STANDARD_DEVIATION 5.69 | 41.3 Years STANDARD_DEVIATION 8.96 | 41.2 Years STANDARD_DEVIATION 10.68 | 42.7 Years STANDARD_DEVIATION 10.37 | 44.3 Years STANDARD_DEVIATION 8.63 | 43.7 Years STANDARD_DEVIATION 7.68 | 57.0 Years STANDARD_DEVIATION 4.36 | 56.3 Years STANDARD_DEVIATION 3.06 | 49.1 Years STANDARD_DEVIATION 8.04 | 43.1 Years STANDARD_DEVIATION 12.54 | 31.3 Years STANDARD_DEVIATION 11.6 | 40.47 Years STANDARD_DEVIATION 10.85 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 5 Participants | 4 Participants | 4 Participants | 4 Participants | 2 Participants | 5 Participants | 4 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 5 Participants | 0 Participants | 5 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 6 Participants | 3 Participants | 67 Participants |
| Sex: Female, Male Male | 13 Participants | 5 Participants | 3 Participants | 4 Participants | 6 Participants | 2 Participants | 4 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 6 Participants | 10 Participants | 3 Participants | 6 Participants | 3 Participants | 3 Participants | 7 Participants | 2 Participants | 3 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk | EG022 affected / at risk | EG023 affected / at risk | EG024 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 10 | 0 / 6 | 2 / 6 | 2 / 6 | 4 / 6 | 3 / 6 | 1 / 2 | 2 / 6 | 1 / 3 | 2 / 3 | 1 / 3 | 2 / 3 | 2 / 3 | 8 / 11 | 7 / 10 | 7 / 8 | 8 / 18 | 5 / 8 | 6 / 8 | 5 / 8 | 6 / 9 | 0 / 3 | 3 / 3 | 5 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 6 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 11 | 0 / 10 | 0 / 8 | 0 / 18 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 3 | 0 / 3 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: Pharmacokinetics (PK) Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 0.0410 h*umol/L | Geometric Coefficient of Variation 32.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 0.0837 h*umol/L | Geometric Coefficient of Variation 27.9 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 1.67 h*umol/L | Geometric Coefficient of Variation 62.7 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 2.78 h*umol/L | Geometric Coefficient of Variation 37.7 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Area Under the Plasma Drug Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 0.246 h*umol/L | Geometric Coefficient of Variation 63.2 |
Primary
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 13.4 h*umol/L | Geometric Coefficient of Variation 22.3 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 17.5 h*umol/L | Geometric Coefficient of Variation 23.5 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 18.4 h*umol/L | Geometric Coefficient of Variation 17 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 26.1 h*umol/L | Geometric Coefficient of Variation 26.5 |
Primary
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 4.74 h*umol/L | Geometric Coefficient of Variation 37.6 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 7.12 h*umol/L | Geometric Coefficient of Variation 37.6 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 12.2 h*umol/L | Geometric Coefficient of Variation 18.9 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 8.94 h*umol/L | Geometric Coefficient of Variation 20.2 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 14.4 h*umol/L | Geometric Coefficient of Variation 20.8 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 19.0 h*umol/L | Geometric Coefficient of Variation 16.3 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 19.4 h*umol/L | Geometric Coefficient of Variation 11.1 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 24.4 h*umol/L | Geometric Coefficient of Variation 7.2 |
Primary
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 1 | 15.1 h*umol/L | Geometric Coefficient of Variation 16.5 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 7 | 20.6 h*umol/L | Geometric Coefficient of Variation 17.9 |
Primary
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 14.7 h*umol/L | Geometric Coefficient of Variation 36.6 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 21.4 h*umol/L | Geometric Coefficient of Variation 26.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 16.1 h*umol/L | Geometric Coefficient of Variation 23.5 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 24.7 h*umol/L | Geometric Coefficient of Variation 22.5 |
Primary
AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 1 | 13.2 h*umol/L | Geometric Coefficient of Variation 32 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 7 | 23.8 h*umol/L | Geometric Coefficient of Variation 37 |
Primary
AUC0-inf of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | 1.05 h*umol/L |
Primary
AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | 17.9 h*umol/L | Geometric Coefficient of Variation 13.4 |
Primary
AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Area under the drug concentration-time curve from time zero to infinity estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 2.26 h*umol/L | Geometric Coefficient of Variation 22.3 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 5.78 h*umol/L | Geometric Coefficient of Variation 4.7 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 7.31 h*umol/L | Geometric Coefficient of Variation 11.1 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 17.5 h*umol/L | — |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 33.4 h*umol/L | Geometric Coefficient of Variation 37 |
Primary
AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Area under the drug concentration-time curve from time zero to infinity for M6, a metabolite of uprifosbuvir, estimated as AUC0-t + Cest/λz, where λz is the terminal elimination rate constant, calculated for the first dose only. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 1.68 h*umol/L | Geometric Coefficient of Variation 47.4 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 5.01 h*umol/L | Geometric Coefficient of Variation 27.2 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 19.8 h*umol/L | Geometric Coefficient of Variation 12.7 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 29.7 h*umol/L | Geometric Coefficient of Variation 32.1 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 8.77 h*umol/L | Geometric Coefficient of Variation 8.4 |
Primary
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 3.19 h*umol/L | Geometric Coefficient of Variation 32.8 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 2.31 h*umol/L | Geometric Coefficient of Variation 31.8 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 4.21 h*umol/L | Geometric Coefficient of Variation 35.2 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 3.51 h*umol/L | Geometric Coefficient of Variation 23.2 |
Primary
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 1 | 10.6 h*umol/L | Geometric Coefficient of Variation 44 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 7 | 9.39 h*umol/L | Geometric Coefficient of Variation 46.1 |
Primary
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 0.347 h*umol/L | Geometric Coefficient of Variation 36.2 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 0.394 h*umol/L | Geometric Coefficient of Variation 51.4 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 0.935 h*umol/L | Geometric Coefficient of Variation 36.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 1.01 h*umol/L | Geometric Coefficient of Variation 52.9 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 2.80 h*umol/L | Geometric Coefficient of Variation 45.4 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 2.42 h*umol/L | Geometric Coefficient of Variation 46.8 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 4.59 h*umol/L | Geometric Coefficient of Variation 22.1 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 5.54 h*umol/L | Geometric Coefficient of Variation 40.1 |
Primary
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 1 | 3.62 h*umol/L | Geometric Coefficient of Variation 34 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 7 | 3.77 h*umol/L | Geometric Coefficient of Variation 21.7 |
Primary
AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 2.00 h*umol/L | Geometric Coefficient of Variation 51.7 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 1.82 h*umol/L | Geometric Coefficient of Variation 43.9 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 3.11 h*umol/L | Geometric Coefficient of Variation 45 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-t of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 2.88 h*umol/L | Geometric Coefficient of Variation 30.4 |
Primary
AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | 1.05 h*umol/L |
Primary
AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | 1.05 h*umol/L | Geometric Coefficient of Variation 48.5 |
Primary
AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 0.0640 h*umol/L | Geometric Coefficient of Variation 39.8 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 0.228 h*umol/L | Geometric Coefficient of Variation 49.1 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 0.341 h*umol/L | Geometric Coefficient of Variation 20.4 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 1.17 h*umol/L | — |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 1.39 h*umol/L | Geometric Coefficient of Variation 35.4 |
Primary
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 1100 nmol/L | Geometric Coefficient of Variation 11.5 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 1550 nmol/L | Geometric Coefficient of Variation 11.4 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 1180 nmol/L | Geometric Coefficient of Variation 11.9 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 1740 nmol/L | Geometric Coefficient of Variation 19.7 |
Primary
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 298 nmol/L | Geometric Coefficient of Variation 34.2 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 471 nmol/L | Geometric Coefficient of Variation 33.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 931 nmol/L | Geometric Coefficient of Variation 14.4 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 641 nmol/L | Geometric Coefficient of Variation 7.6 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 1130 nmol/L | Geometric Coefficient of Variation 22.7 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 1420 nmol/L | Geometric Coefficient of Variation 15.3 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 1560 nmol/L | Geometric Coefficient of Variation 18.9 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 1760 nmol/L | Geometric Coefficient of Variation 10.4 |
Primary
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 1 | 1310 nmol/L | Geometric Coefficient of Variation 7.5 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 7 | 1630 nmol/L | Geometric Coefficient of Variation 14.9 |
Primary
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 1420 nmol/L | Geometric Coefficient of Variation 23.2 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 1010 nmol/L | Geometric Coefficient of Variation 31.5 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 1210 nmol/L | Geometric Coefficient of Variation 21.9 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 1680 nmol/L | Geometric Coefficient of Variation 21.5 |
Primary
Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 7 | 1180 nmol/L | Geometric Coefficient of Variation 33.2 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 1 | 738 nmol/L | Geometric Coefficient of Variation 31.7 |
Primary
Cmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Maximum observed plasma drug concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | 597 nmol/L |
Primary
Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Maximum observed plasma drug concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | 509 nmol/L | Geometric Coefficient of Variation 8.4 |
Primary
Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Maximum observed plasma drug concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 55.0 nmol/L | Geometric Coefficient of Variation 15 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 170 nmol/L | Geometric Coefficient of Variation 7.2 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 279 nmol/L | Geometric Coefficient of Variation 5.2 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 710 nmol/L | — |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 1210 nmol/L | Geometric Coefficient of Variation 33.8 |
Primary
Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Maximum observed plasma drug concentration was obtained. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 63.2 nmol/L | Geometric Coefficient of Variation 19.8 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 146 nmol/L | Geometric Coefficient of Variation 13.6 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 758 nmol/L | Geometric Coefficient of Variation 28.2 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 1190 nmol/L | Geometric Coefficient of Variation 16.6 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 283 nmol/L | Geometric Coefficient of Variation 14.7 |
Primary
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 1440 nmol/L | Geometric Coefficient of Variation 35.9 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 1550 nmol/L | Geometric Coefficient of Variation 47.5 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 1090 nmol/L | Geometric Coefficient of Variation 34.4 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 929 nmol/L | Geometric Coefficient of Variation 26.6 |
Primary
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 1 | 2140 nmol/L | Geometric Coefficient of Variation 39.4 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 7 | 1910 nmol/L | Geometric Coefficient of Variation 42.6 |
Primary
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Maximum observed plasma drug concentration was obtained. All participants were fasted.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 286 nmol/L | Geometric Coefficient of Variation 77.1 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 199 nmol/L | Geometric Coefficient of Variation 45.6 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 587 nmol/L | Geometric Coefficient of Variation 34.9 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 524 nmol/L | Geometric Coefficient of Variation 80.1 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 1360 nmol/L | Geometric Coefficient of Variation 55.5 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 1200 nmol/L | Geometric Coefficient of Variation 59.4 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 2320 nmol/L | Geometric Coefficient of Variation 50.2 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 2490 nmol/L | Geometric Coefficient of Variation 25.7 |
Primary
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 1 | 2300 nmol/L | Geometric Coefficient of Variation 26.6 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 7 | 2320 nmol/L | Geometric Coefficient of Variation 19.9 |
Primary
Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 618 nmol/L | Geometric Coefficient of Variation 45.2 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 537 nmol/L | Geometric Coefficient of Variation 56.4 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 778 nmol/L | Geometric Coefficient of Variation 29.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 717 nmol/L | Geometric Coefficient of Variation 47.2 |
Primary
Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Maximum observed plasma drug concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | 613 nmol/L |
Primary
Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Maximum observed plasma drug concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | 293 nmol/L | Geometric Coefficient of Variation 63 |
Primary
Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Maximum observed plasma drug concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 43.6 nmol/L | Geometric Coefficient of Variation 60.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 122 nmol/L | Geometric Coefficient of Variation 26.4 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 168 nmol/L | Geometric Coefficient of Variation 11.4 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 510 nmol/L | — |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 667 nmol/L | Geometric Coefficient of Variation 15.3 |
Primary
Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A)
Cumulative urine excretion of unchanged M6 in healthy participants was obtained. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A) | 5.93 umol | Standard Deviation 1.42 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A) | 15.2 umol | Standard Deviation 2.5 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A) | 101 umol | Standard Deviation 6.86 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A) | 200 umol | Standard Deviation 37.9 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A) | 31.8 umol | Standard Deviation 5.69 |
Primary
Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A)
Cumulative urine excretion of unchanged MK-3682 in healthy participants was obtained. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A) | 0.280 umol | Standard Deviation 0.08 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A) | 0.586 umol | Standard Deviation 0.164 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A) | 7.73 umol | Standard Deviation 4.67 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A) | 13.1 umol | Standard Deviation 4.16 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A) | 1.56 umol | Standard Deviation 0.397 |
Primary
Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Maximum observed plasma drug concentration was obtained. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 29.6 nmol/L | Geometric Coefficient of Variation 45.3 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 47.7 nmol/L | Geometric Coefficient of Variation 54.4 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 1120 nmol/L | Geometric Coefficient of Variation 47.8 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 1530 nmol/L | Geometric Coefficient of Variation 53.6 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Maximum (Peak) Observed Plasma Drug Concentration (Cmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 119 nmol/L | Geometric Coefficient of Variation 89.2 |
Primary
Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E)
Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype (Gt) 1, HCV-infected participants was obtained.
Time frame: Baseline and 28 days after last dose of study drug (Up to 42 days)
Population: Per-Protocol Population: participants who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Mild hepatic impairment: Gt1b | 1.36 log10 IU/mL | Standard Deviation 0.774 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Baseline | 5.91 log10 IU/mL | Standard Deviation 0.347 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Normal hepatic fcn: Gt1a | 0.96 log10 IU/mL | — |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Normal hepatic fcn: Gt1b | 1.35 log10 IU/mL | — |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Normal hepatic fcn: Gt1 (pooled 1a+1b) | 1.15 log10 IU/mL | Standard Deviation 0.274 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Mild hepatic impairment;Gt1 (pooled 1a+1b) | 1.36 log10 IU/mL | Standard Deviation 0.774 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Normal hepatic fcn: Gt1b | 3.82 log10 IU/mL | Standard Deviation 0.636 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Mild hepatic impairment;Gt1 (pooled 1a+1b) | 3.15 log10 IU/mL | Standard Deviation 0.42 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Mild hepatic impairment: Gt1b | 3.59 log10 IU/mL | — |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Normal hepatic fcn: Gt1 (pooled 1a+1b) | 4.19 log10 IU/mL | Standard Deviation 0.754 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Baseline | 6.16 log10 IU/mL | Standard Deviation 0.633 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Mild hepatic impairment: Gt1a | 2.92 log10 IU/mL | Standard Deviation 0.239 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Normal hepatic fcn: Gt1a | 4.82 log10 IU/mL | Standard Deviation 0.504 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Normal hepatic fcn: Gt1 (pooled 1a+1b) | 4.50 log10 IU/mL | Standard Deviation 0.644 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Normal hepatic fcn: Gt1a | 5.06 log10 IU/mL | Standard Deviation 0.489 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Mild hepatic impairment: Gt1a | 3.60 log10 IU/mL | — |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Mild hepatic impairment;Gt1 (pooled 1a+1b) | 3.16 log10 IU/mL | Standard Deviation 0.989 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Normal hepatic fcn: Gt1b | 4.28 log10 IU/mL | Standard Deviation 0.584 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Mild hepatic impairment: Gt1b | 3.08 log10 IU/mL | Standard Deviation 1.06 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) | Baseline | 6.14 log10 IU/mL | Standard Deviation 0.356 |
Primary
Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 0.839 hours | Geometric Coefficient of Variation 27.3 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 0.872 hours | Geometric Coefficient of Variation 33.7 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 1.05 hours | Geometric Coefficient of Variation 25 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 1.13 hours | Geometric Coefficient of Variation 31.6 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 0.979 hours | Geometric Coefficient of Variation 36.6 |
Primary
Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE
The percentage of participants who discontinued study drug due to an AE is presented.
Time frame: Up to 14 days
Population: Safety Population: all participants who received at least one dose of the study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group A: Placebo (Cohort 6a) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Groups C & D: Placebo (Pooled) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
| Group F: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE | 0.0 Percentage of Participants |
Primary
Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered study drug, and that does not necessarily have a causal relationship with the study drug(s). An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug(s), whether or not related to study drug(s). The percentage of participants who experienced at least one AE is presented.
Time frame: Up to 42 days
Population: Safety Population: all participants who received at least one dose of the study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 50.0 Percentage of Participants |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 33.3 Percentage of Participants |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 33.3 Percentage of Participants |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 66.7 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 50.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 33.3 Percentage of Participants |
| Group A: Placebo (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 50.0 Percentage of Participants |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 33.3 Percentage of Participants |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 66.7 Percentage of Participants |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 33.3 Percentage of Participants |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 66.7 Percentage of Participants |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 66.7 Percentage of Participants |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 72.7 Percentage of Participants |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 70.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 87.5 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 44.4 Percentage of Participants |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 62.5 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 75.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 62.5 Percentage of Participants |
| Groups C & D: Placebo (Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 66.7 Percentage of Participants |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 100.0 Percentage of Participants |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 62.5 Percentage of Participants |
| Group F: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) | 37.5 Percentage of Participants |
Primary
Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality
Laboratory abnormalities were graded using the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. Treatment-emergent AEs (TEAEs)were graded as: Grade 1: Mild TEAE as Worst Severity; Grade 2: Moderate TEAE as Worst Severity; Grade 3: Severe TEAE as Worst Severity; Grade 4: Potentially Life-Threatening TEAE as Worst Severity; Grade 5: TEAE Leading to Death. The percentage of participants who experienced at least one Grade 1, 2, 3, 4 or 5 laboratory abnormality is presented.
Time frame: Up to 42 days
Population: Safety Population: all participants who received at least one dose of the study drug
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 50.00 Percentage of Participants |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 16.7 Percentage of Participants |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 16.7 Percentage of Participants |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 16.7 Percentage of Participants |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 16.7 Percentage of Participants |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 50.0 Percentage of Participants |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 16.7 Percentage of Participants |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 33.3 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 16.7 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 33.3 Percentage of Participants |
| Group A: Placebo (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 50.0 Percentage of Participants |
| Group A: Placebo (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group A: Placebo (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group A: Placebo (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group A: Placebo (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 33.3 Percentage of Participants |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 66.7 Percentage of Participants |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 33.3 Percentage of Participants |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 66.7 Percentage of Participants |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 33.3 Percentage of Participants |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 66.7 Percentage of Participants |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 9.1 Percentage of Participants |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 45.5 Percentage of Participants |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 18.2 Percentage of Participants |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 10.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 60.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 37.5 Percentage of Participants |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 50.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 33.3 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 5.6 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 5.6 Percentage of Participants |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 62.5 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 37.5 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 37.5 Percentage of Participants |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 25.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 25.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 12.5 Percentage of Participants |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Groups C & D: Placebo (Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Groups C & D: Placebo (Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 33.3 Percentage of Participants |
| Groups C & D: Placebo (Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Groups C & D: Placebo (Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 33.3 Percentage of Participants |
| Groups C & D: Placebo (Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 100.0 Percentage of Participants |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 12.5 Percentage of Participants |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 12.5 Percentage of Participants |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 37.5 Percentage of Participants |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group F: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 2 | 37.5 Percentage of Participants |
| Group F: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 1 | 0.0 Percentage of Participants |
| Group F: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 3 | 0.0 Percentage of Participants |
| Group F: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 5 | 0.0 Percentage of Participants |
| Group F: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality | Grade 4 | 0.0 Percentage of Participants |
Primary
Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE)
An SAE was defined as any untoward medical occurrence that at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. The percentage of participants who experienced at least one SAE is presented.
Time frame: Up to 42 days
Population: Safety Population: all participants who received at least one dose of the study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group A: Placebo (Cohort 6a) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Groups C & D: Placebo (Pooled) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
| Group F: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) | 0.0 Percentage of Participants |
Primary
Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT)
A DLT was defined as any of the following events: Any SAE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 clinical AE considered by the investigator to be at least reasonably or possibly related to study drug; Any Grade 3 confirmed laboratory abnormalities considered by the investigator to be at least reasonably or possibly related to study drug, except for asymptomatic Grade ¾ cholesterol and triglyceride; Any clinical or laboratory AE of any intensity that is considered by the investigator to be at least reasonably or possibly related to study drug that necessitates permanent discontinuation of study drug; Confirmed increase in QT interval corrected for heart rate using Fridericia's (QTcF) formula ≥60 msec over Baseline or an absolute QTcF ≥500 msec.
Time frame: Up to 13 days
Population: Safety Population: all participants who received at least one dose of the study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group A: Placebo (Cohort 6a) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 10 mg (Cohort 1b) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 25 mg (Cohort 2b) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 50 mg (Cohort 3b) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 150 mg (Cohort 4b) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group B: Uprifosbuvir 300 mg (Cohort 5b) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 50 mg (Capsule) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 150 mg (Capsule) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 250 mg (Capsule) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Capsule) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 400 mg (Capsule) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Groups C & D: Uprifosbuvir 450 mg (Tablet) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Groups C & D: Placebo (Pooled) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 150 mg (Cohort 1e) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 300 mg (Cohort 2e) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group E: Uprifosbuvir 450 mg (Cohort 3e) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| Group F: Uprifosbuvir 300 mg (Tablet) | Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) | 0.0 Percentage of Participants |
Primary
Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Reduction in HCV RNA from baseline on Day 8 following uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-infected participants was obtained.
Time frame: Baseline and Day 8
Population: Per-Protocol Population: participants who complied with the protocol sufficiently to ensure that these data were likely to exhibit the effects of treatment, according to the underlying scientific model.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Baseline | 5.82 log10 IU/mL | Standard Deviation 0.879 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 8 | 0.78 log10 IU/mL | Standard Deviation 0.44 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 8 | 2.49 log10 IU/mL | Standard Deviation 0.733 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Baseline | 6.00 log10 IU/mL | Standard Deviation 0.63 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Baseline | 6.16 log10 IU/mL | Standard Deviation 0.633 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 8 | 4.22 log10 IU/mL | Standard Deviation 0.614 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 8 | 4.39 log10 IU/mL | Standard Deviation 0.433 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Baseline | 6.11 log10 IU/mL | Standard Deviation 0.54 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 8 | 0.42 log10 IU/mL | Standard Deviation 0.229 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Baseline | 6.27 log10 IU/mL | Standard Deviation 0.485 |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Baseline | 5.92 log10 IU/mL | Standard Deviation 0.838 |
| Group A: Uprifosbuvir 300 mg (Cohort 5a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 8 | 3.34 log10 IU/mL | Standard Deviation 0.643 |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 8 | 4.50 log10 IU/mL | Standard Deviation 0.644 |
| Group A: Uprifosbuvir 300 mg (Cohort 6a) | Reduction in HCV RNA From Baseline on Day 8 Following Uprifosbuvir 50-450 mg for 7 Days in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Baseline | 5.97 log10 IU/mL | Standard Deviation 0.739 |
Primary
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | 27.5 hours | Geometric Coefficient of Variation 9.3 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | 26.2 hours | Geometric Coefficient of Variation 24.8 |
Primary
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | 25.5 hours | Geometric Coefficient of Variation 16.8 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | 28.9 hours | Geometric Coefficient of Variation 15.2 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | 32.6 hours | Geometric Coefficient of Variation 12.7 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | 35.8 hours | Geometric Coefficient of Variation 17.8 |
Primary
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | 32.2 hours | Geometric Coefficient of Variation 10.3 |
Primary
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | 32.4 hours | Geometric Coefficient of Variation 7.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | 30.8 hours | Geometric Coefficient of Variation 26.8 |
Primary
t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | 38.9 hours | Geometric Coefficient of Variation 17.7 |
Primary
t1/2 of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | 24.0 hours |
Primary
t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | 27.1 hours | Geometric Coefficient of Variation 9.1 |
Primary
t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 20.1 hours | Geometric Coefficient of Variation 3.4 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 21.2 hours | Geometric Coefficient of Variation 4.8 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 21.7 hours | Geometric Coefficient of Variation 19.8 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 26.9 hours | — |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 28.0 hours | Geometric Coefficient of Variation 12.1 |
Primary
t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 22.5 hours | Geometric Coefficient of Variation 6.2 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 24.6 hours | Geometric Coefficient of Variation 12.8 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 29.1 hours | Geometric Coefficient of Variation 15.5 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 28.8 hours | Geometric Coefficient of Variation 14.2 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 22.9 hours | Geometric Coefficient of Variation 14 |
Primary
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | 1.18 hours | Geometric Coefficient of Variation 27.2 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | 2.38 hours | Geometric Coefficient of Variation 34.3 |
Primary
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | 1.04 hours | Geometric Coefficient of Variation 25.1 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | 1.11 hours | Geometric Coefficient of Variation 22.5 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | 154. hours | Geometric Coefficient of Variation 34 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | 2.58 hours | Geometric Coefficient of Variation 40.3 |
Primary
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C) | 2.50 hours | Geometric Coefficient of Variation 55.9 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C) | 3.64 hours | Geometric Coefficient of Variation 54.8 |
Primary
t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F) | 4.30 hours | Geometric Coefficient of Variation 52.8 |
Primary
t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | 1.16 hours |
Primary
t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | 1.63 hours | Geometric Coefficient of Variation 31.9 |
Primary
t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B)
The time measured for the plasma concentration to decrease by one half (t1/2) was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 1.36 hours | Geometric Coefficient of Variation 52.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 0.926 hours | Geometric Coefficient of Variation 34.5 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 1.09 hours | Geometric Coefficient of Variation 32.5 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 1.11 hours | — |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 1.59 hours | Geometric Coefficient of Variation 1.7 |
Primary
Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time to maximum plasma concentration was obtained. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 0.80 hours | Full Range 32.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 1.00 hours | Full Range 27.9 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 0.76 hours | Full Range 62.7 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 0.50 hours | Full Range 37.7 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 1.00 hours | Full Range 63.2 |
Primary
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1,HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
Time to maximum plasma concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1,HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 3.00 hours | Full Range 32.8 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1,HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 2.00 hours | Full Range 31.8 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1,HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 4.00 hours | Full Range 35.2 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1,HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 4.00 hours | Full Range 23.2 |
Primary
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D)
Time to maximum plasma concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 4.00 hours | Full Range 51.4 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 2.00 hours | Full Range 36.2 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 2.00 hours | Full Range 36.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 3.00 hours | Full Range 52.9 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 3.00 hours | Full Range 45.4 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 3.00 hours | Full Range 46.8 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 1 | 4.00 hours | Full Range 40.1 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-Infected Participants (Groups C and D) | Day 7 | 4.00 hours | Full Range 22.1 |
Primary
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Time to maximum plasma concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 1 | 3.00 hours | Full Range 3.77 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 7 | 2.50 hours | Full Range 21.7 |
Primary
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C)
Time to maximum plasma concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 4.00 hours | Full Range 51.7 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 4.00 hours | Full Range 43.9 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 7 | 4.00 hours | Full Range 30.4 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants (Group C) | Day 1 | 4.00 hours | Full Range 45 |
Primary
Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F)
Time to maximum plasma concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 1 | 10.00 hours | Full Range 44 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-Infected Participants, With Itraconazole (Group F) | Day 7 | 4.00 hours | Full Range 46.1 |
Primary
Tmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time to maximum plasma concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Single Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-Infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | 4.00 hours |
Primary
Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time to maximum plasma concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | 6.00 hours | Full Range 48.5 |
Primary
Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B)
Time to maximum plasma concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 4.00 hours | Full Range 39.8 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 4.00 hours | Full Range 49.1 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 2.05 hours | Full Range 20.4 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 3.52 hours | — |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) | 4.00 hours | Full Range 35.4 |
Primary
Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A)
Time to maximum plasma concentration was obtained. All participants were fasted.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 3.01 hours | Full Range 32.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 3.50 hours | Full Range 27.9 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 2.53 hours | Full Range 62.7 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 3.50 hours | Full Range 37.7 |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) | 4.00 hours | Full Range 63.2 |
Primary
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e)
AUC0-t was calculated using linear log trapezoidal summation from time zero to last measurable concentration.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 1.00 hours | Full Range 32.8 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 1.00 hours | Full Range 31.8 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 1 | 1.00 hours | Full Range 35.2 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as Capsule or Tablet Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 2e and Cohort 3e) | Day 7 | 1.00 hours | Full Range 23.2 |
Primary
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D)
Time to maximum plasma concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Day 1 | 0.85 hours | Full Range 51.4 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Day 7 | 0.97 hours | Full Range 36.2 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Day 7 | 0.50 hours | Full Range 36.7 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Day 1 | 0.50 hours | Full Range 52.9 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Day 7 | 0.50 hours | Full Range 46.8 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Day 1 | 1.00 hours | Full Range 45.4 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Day 1 | 0.50 hours | Full Range 40.1 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Genotype 1, 2 and 3, HCV-infected Participants (Groups C and D) | Day 7 | 0.50 hours | Full Range 22.1 |
Primary
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a)
Maximum observed plasma drug concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 1 | 0.75 hours | Full Range 26.6 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Capsule Formulation in Healthy Participants (Group A - Cohort 6a) | Day 7 | 0.50 hours | Full Range 19.9 |
Primary
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C)
Time to maximum plasma concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C) | Day 1 | 1.00 hours | Full Range 51.7 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C) | Day 7 | 0.50 hours | Full Range 43.9 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C) | Day 1 | 2.00 hours | Full Range 45 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants (Group C) | Day 7 | 0.50 hours | Full Range 30.4 |
Primary
Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F)
Time to maximum plasma concentration was obtained.
Time frame: Days 1 & 7: predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F) | Day 1 | 2.00 hours | Full Range 44 |
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Multiple Doses of Uprifosbuvir Once-Daily x 7 Days as the Tablet Formulation in Genotype 1, HCV-infected Participants, With Itraconazole (Group F) | Day 7 | 1.00 hours | Full Range 46.1 |
Primary
Tmax of Uprifosbuvir After Singe Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e)
Time to maximum plasma concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Singe Dose of Uprifosbuvir as Capsule Formulation in Genotype 1, HCV-infected Participants With Mildly Impaired Hepatic Function (Child Pugh Class A) (Group E - Cohort 1e) | 0.75 hours |
Primary
Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a)
Time to maximum plasma concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) | 3.04 hours | Full Range 47.8 |
Primary
Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B)
Time to maximum plasma concentration was obtained.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 36, 48, 72, 96, and 120 hours postdose
Population: PK Population: a subpopulation of the per-protocol population, selecting all participants exposed to uprifosbuvir who had available and evaluable data (e.g., excluding deviations and/or other events that could have an impact on the PK analysis).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Group A: Placebo (Cohort 1a-Cohort 5a - Pooled) | Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 0.50 hours | Full Range 39.8 |
| Group A: Uprifosbuvir 10 mg (Cohort 1a) | Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 1.00 hours | Full Range 49.1 |
| Group A: Uprifosbuvir 25 mg (Cohort 2a) | Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 1.00 hours | Full Range 20.4 |
| Group A: Uprifosbuvir 50 mg (Cohort 3a) | Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 0.76 hours | — |
| Group A: Uprifosbuvir 150 mg (Cohort 4a) (Fasted and Fed) | Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) | 1.00 hours | Full Range 35.4 |