Phase 2
Completed N=178
Single and Multiple Dose Study of Uprifosbuvir (MK-3682/IDX21437) in Healthy and Hepatitis C Virus (HCV)-Infected Participants (MK-3682-001)
Chronic Hepatitis C
Source: ClinicalTrials.gov NCT01974687 ↗
Enrolled (actual)
178
Serious AEs
0.0%
Results posted
Sep 2018
Primary outcomePrimary: Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) — 50.0; 0.0; 33.3; 33.3 Percentage of Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Event (AE) |
50.0; 0.0; 33.3; 33.3; 66.7; 50.0 | — |
| PRIMARY Percentage of Participants Who Experienced at Least One Treatment-emergent Serious AE (SAE) |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Percentage of Participants Who Experienced a Treatment-emergent Dose-limiting Toxicity (DLT) |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| PRIMARY Percentage of Participants Who Experienced at Least One Treatment-emergent Grade 1, 2, 3, 4 or 5 Laboratory Abnormality |
50.00; 0.0; 16.7; 16.7; 50.0; 33.3 | — |
| PRIMARY Percentage of Participants Who Discontinued Study Drug Due to a Treatment-emergent AE |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| 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) |
0.0410; 0.0837; 1.67; 2.78; 0.246 | — |
| PRIMARY 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 | — |
| 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) |
3.62; 3.77 | — |
| PRIMARY AUC0-t of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) |
0.0640; 0.228; 0.341; 1.17; 1.39 | — |
| 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) |
0.394; 1.01; 2.80; 5.54; 0.347; 0.935 | — |
| 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) |
2.00; 3.11; 1.82; 2.88 | — |
| 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) |
1.05 | — |
| 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) |
3.19; 4.21; 2.31; 3.51 | — |
| 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) |
10.6; 9.39 | — |
| PRIMARY 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; 47.7; 1120; 1530; 119 | — |
| PRIMARY Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) |
293 | — |
| 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) |
2300; 2320 | — |
| PRIMARY Cmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) |
43.6; 122; 168; 510; 667 | — |
| 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) |
286; 524; 1360; 2320; 199; 587 | — |
| 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) |
618; 778; 537; 717 | — |
| 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) |
613 | — |
| 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) |
1440; 1090; 1550; 929 | — |
| 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) |
2140; 1910 | — |
| PRIMARY Time to Maximum Plasma Concentration (Tmax) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) |
0.80; 1.00; 0.76; 0.50; 1.00 | — |
| PRIMARY Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) |
3.04 | — |
| 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) |
0.75; 0.50 | — |
| PRIMARY Tmax of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) |
0.50; 1.00; 1.00; 0.76; 1.00 | — |
| 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) |
0.85; 0.50; 1.00; 0.50; 0.97; 0.50 | — |
| 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) |
1.00; 2.00; 0.50; 0.50 | — |
| 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) |
0.75 | — |
| 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) |
1.00; 1.00; 1.00; 1.00 | — |
| 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) |
2.00; 1.00 | — |
| PRIMARY Observed Terminal Half-Life (t1/2) of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) |
0.839; 0.872; 1.05; 1.13; 0.979 | — |
| PRIMARY 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 | — |
| PRIMARY t1/2 of Uprifosbuvir After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-infected Participants (Group B) |
1.36; 0.926; 1.09; 1.11; 1.59 | — |
| 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) |
1.04; 1.11; 154.; 2.58 | — |
| 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) |
2.50; 3.64 | — |
| 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) |
1.16 | — |
| 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) |
1.18; 2.38 | — |
| 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) |
4.30 | — |
| PRIMARY AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) |
1.68; 5.01; 19.8; 29.7; 8.77 | — |
| PRIMARY 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 | — |
| 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) |
15.1; 20.6 | — |
| PRIMARY AUC0-inf of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) |
2.26; 5.78; 7.31; 17.5; 33.4 | — |
| 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) |
4.74; 8.94; 14.4; 19.4; 7.12; 12.2 | — |
| 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) |
14.7; 16.1; 21.4; 24.7 | — |
| 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) |
1.05 | — |
| 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) |
13.4; 18.4; 17.5; 26.1 | — |
| 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) |
13.2; 23.8 | — |
| PRIMARY Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) |
63.2; 146; 758; 1190; 283 | — |
| PRIMARY Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) |
509 | — |
| 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) |
1310; 1630 | — |
| PRIMARY Cmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) |
55.0; 170; 279; 710; 1210 | — |
| 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) |
298; 641; 1130; 1560; 471; 931 | — |
| 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) |
1010; 1210; 1420; 1680 | — |
| 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) |
597 | — |
| 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) |
1100; 1180; 1550; 1740 | — |
| 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) |
738; 1180 | — |
| PRIMARY Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) |
3.01; 3.50; 2.53; 3.50; 4.00 | — |
| PRIMARY Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Fed State in Healthy Participants (Group A - Cohort 4a) |
6.00 | — |
| 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) |
3.00; 2.50 | — |
| PRIMARY Tmax of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) |
4.00; 4.00; 2.05; 3.52; 4.00 | — |
| 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) |
4.00; 3.00; 3.00; 4.00; 2.00; 2.00 | — |
| 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) |
4.00; 4.00; 4.00; 4.00 | — |
| 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) |
4.00 | — |
| 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) |
3.00; 4.00; 2.00; 4.00 | — |
| 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) |
10.00; 4.00 | — |
| PRIMARY t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Healthy Participants (Group A) |
22.5; 24.6; 29.1; 28.8; 22.9 | — |
| PRIMARY 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 | — |
| 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) |
32.2 | — |
| PRIMARY t1/2 of M6 After Single Dose of Uprifosbuvir as the Capsule Formulation in Genotype 1, HCV-Infected Participants (Group B) |
20.1; 21.2; 21.7; 26.9; 28.0 | — |
| 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) |
25.5; 28.9; 32.6; 35.8 | — |
| 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 (Group C) |
32.4; 30.8 | — |
| 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) |
24.0 | — |
| 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) |
27.5; 26.2 | — |
| 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) |
38.9 | — |
| PRIMARY Cumulative Urine Excretion of Unchanged Uprifosbuvir in Healthy Participants (Group A) |
0.280; 0.586; 7.73; 13.1; 1.56 | — |
| PRIMARY Cumulative Urine Excretion of Unchanged M6 in Healthy Participants (Group A) |
5.93; 15.2; 101; 200; 31.8 | — |
| 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) |
5.82; 6.00; 6.16; 6.11; 6.27; 5.92 | — |
| PRIMARY Maximum Reduction in log10 HCV RNA From Baseline - Normal Participants (From Groups B and C) vs. Mild Hepatic Impairment Participants (Group E) |
5.91; 6.16; 6.14; 0.96; 4.82; 5.06 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT01974687). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.