A Study of Safety and Efficacy of Vaniprevir Administered With Pegylated-Interferon and Ribavirin in Japanese Participants With Chronic Hepatitis C Infection (7009-016)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00880763
Collaborator
(none)
90
4
34.1
Study Details
Study Description
Brief Summary
The study evaluates safety and efficacy of vaniprevir (MK7009), when administered with Pegylated-Interferon (peg-IFN) and Ribavirin, in Japanese patients with Hepatitis C infection. The primary hypotheses are that 1.) the proportion of patients achieving rapid viral response (RVR) in one or more of the vaniprevir treatment groups is superior to that in the placebo group, when each is administered concomitantly with pegylated interferon (peg-IFN) α-2a and ribavirin; and 2.) vaniprevir at the studied doses is well tolerated compared with placebo, when each is administered concomitantly with peg-IFN α-2a and ribavirin for 28 days.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
90 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase II Randomized Placebo-controlled Study to Evaluate the Safety and Efficacy of MK-7009 Administered Concomitantly With Pegylated-Interferon and Ribavirin for 28 Days in Japanese Treatment-Experienced Patients With Chronic Hepatitis C Infection
Actual Study Start Date
:
Apr 20, 2009
Actual Primary Completion Date
:
Jun 3, 2010
Actual Study Completion Date
:
Feb 23, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Vaniprevir 200 mg + peg-IFN + ribavirin Participants will receive vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
Drug: Vaniprevir
Vaniprevir oral capsule administered twice daily (200, 600 or 1200 mg/day) for 28 days
Other Names:
Drug: Pegylated Interferon (peg-IFN)
Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks
Drug: Ribavirin
Open-label ribavirin (sourced locally) administered orally twice daily, 600 to 1000 mg/day, for 6 weeks
|
| Experimental: Vaniprevir 600 mg + peg-IFN + ribavirin Participants will receive vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
Drug: Vaniprevir
Vaniprevir oral capsule administered twice daily (200, 600 or 1200 mg/day) for 28 days
Other Names:
Drug: Pegylated Interferon (peg-IFN)
Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks
Drug: Ribavirin
Open-label ribavirin (sourced locally) administered orally twice daily, 600 to 1000 mg/day, for 6 weeks
|
| Experimental: Vaniprevir 1200 mg + peg-IFN + ribavirin Participants will receive vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
Drug: Vaniprevir
Vaniprevir oral capsule administered twice daily (200, 600 or 1200 mg/day) for 28 days
Other Names:
Drug: Pegylated Interferon (peg-IFN)
Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks
Drug: Ribavirin
Open-label ribavirin (sourced locally) administered orally twice daily, 600 to 1000 mg/day, for 6 weeks
|
| Placebo Comparator: Placebo + peg-IFN + ribavirin Participants will receive placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants will continue peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
Drug: Pegylated Interferon (peg-IFN)
Open-label peg-IFN alfa-2a subcutaneous injection (sourced locally) administered weekly, 180 micrograms, for 6 weeks
Drug: Ribavirin
Open-label ribavirin (sourced locally) administered orally twice daily, 600 to 1000 mg/day, for 6 weeks
Drug: Comparator: Placebo
Placebo to vaniprevir oral capsule twice daily for 28 days
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Achieving Rapid Viral Response [Week 4]
Rapid viral response (RVR) is defined as undetectable hepatitis C virus ribonucleic acid (HCV RNA) at Week 4. Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The limit of quantification was 1.2 log IU/mL (15 IU/mL) and the limit of detection was <1.2 log IU/mL, but with no specific value. The Data-As-Observed (DAO) approach was used to handle missing data.
Secondary Outcome Measures
- Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4 [Baseline and Week 4]
Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data.
- Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4 [Baseline and Week 4]
Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data.
- Change From Baseline in HCV RNA in log10 at Week 4 [Baseline and Week 4]
Change from baseline in HCV RNA at Week 4 was calculated by subtracting Week 4 HCV RNA level from Baseline HCV RNA level. HCV RNA is measured as International Units per milliliter (IU/mL). Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data.
- Number of Participants Who Experienced at Least One Adverse Event [Up to 6 weeks]
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
- Number of Participants Who Discontinued Study Drug Due to an Adverse Event [Up to 6 weeks]
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
to 64 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Has chronic genotype 1 Hepatitis C infection
Exclusion Criteria:
-
Has not tolerated previous course of peg-IFN and ribavirin
-
Has HIV
-
Has Hepatitis B
-
Has a history of clinically significant medical condition that may interfere with the study (e.g., stroke or chronic seizures or major neurological disorder) or is contraindicated for treatment with peg-IFN and ribavirin
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT00880763
Other Study ID Numbers:
- 7009-016
- 2009_576
First Posted:
Apr 14, 2009
Last Update Posted:
Oct 9, 2018
Last Verified:
Sep 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Initial treatment period (Part 1) includes up through Week 6; Extension period (Part 2) includes from Week 6 through Week 96. |
| Arm/Group Title | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin |
|---|---|---|---|---|
| Arm/Group Description | Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Period Title: Initial Treatment Period (Part 1) | ||||
| STARTED | 23 | 22 | 23 | 22 |
| COMPLETED | 23 | 22 | 23 | 22 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
| Period Title: Initial Treatment Period (Part 1) | ||||
| STARTED | 23 | 22 | 23 | 22 |
| COMPLETED | 23 | 19 | 20 | 19 |
| NOT COMPLETED | 0 | 3 | 3 | 3 |
Baseline Characteristics
| Arm/Group Title | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Total of all reporting groups |
| Overall Participants | 23 | 22 | 23 | 22 | 90 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
55.0
(6.5)
|
54.3
(7.6)
|
56.3
(7.8)
|
54.7
(6.9)
|
55.1
(7.1)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
12
52.2%
|
7
31.8%
|
12
52.2%
|
14
63.6%
|
45
50%
|
| Male |
11
47.8%
|
15
68.2%
|
11
47.8%
|
8
36.4%
|
45
50%
|
| Region of Enrollment (Number) [Number] | |||||
| Japan |
23
100%
|
22
100%
|
23
100%
|
22
100%
|
90
100%
|
| Genotype (Number) [Number] | |||||
| Genotype 1a |
1
4.3%
|
1
4.5%
|
0
0%
|
1
4.5%
|
3
3.3%
|
| Genotype 1b |
22
95.7%
|
21
95.5%
|
23
100%
|
21
95.5%
|
87
96.7%
|
Outcome Measures
| Title | Percentage of Participants Achieving Rapid Viral Response |
|---|---|
| Description | Rapid viral response (RVR) is defined as undetectable hepatitis C virus ribonucleic acid (HCV RNA) at Week 4. Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The limit of quantification was 1.2 log IU/mL (15 IU/mL) and the limit of detection was <1.2 log IU/mL, but with no specific value. The Data-As-Observed (DAO) approach was used to handle missing data. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol population excludes participants for important deviations from the protocol that may substantially affect the results of the primary efficacy analysis. |
| Arm/Group Title | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin |
|---|---|---|---|---|
| Arm/Group Description | Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Measure Participants | 22 | 20 | 21 | 20 |
| Number [Percentage of participants] |
86.4
375.7%
|
95.0
431.8%
|
76.2
331.3%
|
20.0
90.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 200 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in percent |
| Estimated Value | 65.1 | |
| Confidence Interval |
(2-Sided) 95% 37.0 to 82.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using Miettinen and Nurminen method adjusting the strata (participation of Intensive-pharmacokinetic cohort vs. not). | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 600 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in percent |
| Estimated Value | 74.5 | |
| Confidence Interval |
(2-Sided) 95% 47.6 to 89.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using Miettinen and Nurminen method adjusting the strata (participation of Intensive-pharmacokinetic cohort vs. not). | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 1200 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Miettinen and Nurminen | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in percent |
| Estimated Value | 55.4 | |
| Confidence Interval |
(2-Sided) 95% 24.9 to 76.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using Miettinen and Nurminen method adjusting the strata (participation of Intensive-pharmacokinetic cohort vs. not). | |
| Title | Percentage of Participants Achieving a > or = 2-log10 Decrease in HCV RNA From Baseline to Week 4 |
|---|---|
| Description | Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol population excludes participants for important deviations from the protocol that may substantially affect the results of the primary efficacy analysis. |
| Arm/Group Title | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin |
|---|---|---|---|---|
| Arm/Group Description | Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Measure Participants | 22 | 20 | 21 | 20 |
| Number [Percentage of participants] |
100
434.8%
|
100
454.5%
|
100
434.8%
|
95
431.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 200 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in percent |
| Estimated Value | 4.8 | |
| Confidence Interval |
(2-Sided) 95% -11.3 to 24.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using Miettinen and Nurminen method adjusting the strata (participation of Intensive-pharmacokinetic cohort vs. not) | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 600 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in percent |
| Estimated Value | 4.9 | |
| Confidence Interval |
(2-Sided) 95% -12.4 to 24.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using Miettinen and Nurminen method adjusting the strata (participation of Intensive-pharmacokinetic cohort vs. not) | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 1200 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in percent |
| Estimated Value | 4.8 | |
| Confidence Interval |
(2-Sided) 95% -12.0 to 24.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using Miettinen and Nurminen method adjusting the strata (participation of Intensive-pharmacokinetic cohort vs. not) | |
| Title | Percentage of Participants Achieving a > or = 3-log10 Decrease in HCV RNA From Baseline to Week 4 |
|---|---|
| Description | Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol population excludes participants for important deviations from the protocol that may substantially affect the results of the primary efficacy analysis. |
| Arm/Group Title | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin |
|---|---|---|---|---|
| Arm/Group Description | Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Measure Participants | 22 | 20 | 21 | 20 |
| Number [Percentage of participants] |
100
434.8%
|
100
454.5%
|
100
434.8%
|
85
386.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 200 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in percent |
| Estimated Value | 14.5 | |
| Confidence Interval |
(2-Sided) 95% -2.5 to 36.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using Miettinen and Nurminen method adjusting the strata (participation of Intensive-pharmacokinetic cohort vs. not) | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 600 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in percent |
| Estimated Value | 14.6 | |
| Confidence Interval |
(2-Sided) 95% -3.4 to 36.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using Miettinen and Nurminen method adjusting the strata (participation of Intensive-pharmacokinetic cohort vs. not) | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 1200 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Adjusted difference in percent |
| Estimated Value | 14.4 | |
| Confidence Interval |
(2-Sided) 95% -3.3 to 36.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using Miettinen and Nurminen method adjusting the strata (participation of Intensive-pharmacokinetic cohort vs. not) | |
| Title | Change From Baseline in HCV RNA in log10 at Week 4 |
|---|---|
| Description | Change from baseline in HCV RNA at Week 4 was calculated by subtracting Week 4 HCV RNA level from Baseline HCV RNA level. HCV RNA is measured as International Units per milliliter (IU/mL). Serum HCV RNA levels were measured using Roche COBAS TaqMan HCV Auto assay. The DAO approach was used to handle missing data. |
| Time Frame | Baseline and Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol population excludes participants for important deviations from the protocol that may substantially affect the results of the primary efficacy analysis. |
| Arm/Group Title | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin |
|---|---|---|---|---|
| Arm/Group Description | Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Measure Participants | 22 | 20 | 21 | 20 |
| Baseline |
6.6
(0.6)
|
6.6
(0.6)
|
6.6
(0.8)
|
6.6
(0.5)
|
| Change from Baseline |
-6.5
(0.6)
|
-6.6
(0.6)
|
-6.3
(0.8)
|
-4.7
(1.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 200 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares mean |
| Estimated Value | -1.8 | |
| Confidence Interval |
(2-Sided) 95% -2.3 to -1.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using a longitudinal data analysis model including treatment, time and the interaction of time by treatment, with a restriction of the same baseline mean across treatment groups. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 600 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares mean |
| Estimated Value | -1.9 | |
| Confidence Interval |
(2-Sided) 95% -2.4 to -1.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using a longitudinal data analysis model including treatment, time and the interaction of time by treatment, with a restriction of the same baseline mean across treatment groups. | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Vaniprevir 1200 mg + Peg-IFN + Ribavirin, Placebo + Peg-IFN + Ribavirin |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in least squares mean |
| Estimated Value | -1.6 | |
| Confidence Interval |
(2-Sided) 95% -2.2 to -1.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Computed using a longitudinal data analysis model including treatment, time and the interaction of time by treatment, with a restriction of the same baseline mean across treatment groups. | |
| Title | Number of Participants Who Experienced at Least One Adverse Event |
|---|---|
| Description | An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. |
| Time Frame | Up to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The All Participants as Treated population consists of all randomized participants who received at least one dose of study treatment. Participants are included in the treatment group corresponding to the study treatment they actually received. |
| Arm/Group Title | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin |
|---|---|---|---|---|
| Arm/Group Description | Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Measure Participants | 23 | 22 | 23 | 22 |
| Number [Participants] |
23
100%
|
22
100%
|
23
100%
|
22
100%
|
| Title | Number of Participants Who Discontinued Study Drug Due to an Adverse Event |
|---|---|
| Description | An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. |
| Time Frame | Up to 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The All Participants as Treated population consists of all randomized participants who received at least one dose of study treatment. Participants are included in the treatment group corresponding to the study treatment they actually received. |
| Arm/Group Title | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin |
|---|---|---|---|---|
| Arm/Group Description | Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. |
| Measure Participants | 23 | 22 | 23 | 22 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Non-serious adverse events: up to 6 weeks (Part 1 only); Serious adverse events: up to 96 weeks (Parts 1 and 2 including 24-week follow-up period) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All participants as treated population consists of all randomized participants who received at least one dose of study. Participants are included in the treatment group corresponding to the study treatment they actually received. | |||||||
| Arm/Group Title | Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin | ||||
| Arm/Group Description | Participants received vaniprevir 100 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 300 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received vaniprevir 600 mg twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | Participants received placebo twice daily in combination with peg-IFN and ribavirin for 28 days. Participants continued peg-IFN and ribavirin through Week 6 or, at the investigators discretion, up to Week 72. | ||||
All Cause Mortality |
||||||||
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/23 (8.7%) | 2/22 (9.1%) | 0/23 (0%) | 2/22 (9.1%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Disseminated intravascular coagulation | 0/23 (0%) | 0 | 0/22 (0%) | 0 | 0/23 (0%) | 0 | 1/22 (4.5%) | 1 |
| Eye disorders | ||||||||
| Cataract | 0/23 (0%) | 0 | 0/22 (0%) | 0 | 0/23 (0%) | 0 | 1/22 (4.5%) | 1 |
| Gastrointestinal disorders | ||||||||
| Inguinal hernia | 0/23 (0%) | 0 | 1/22 (4.5%) | 1 | 0/23 (0%) | 0 | 0/22 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| Hepatic steatosis | 1/23 (4.3%) | 1 | 0/22 (0%) | 0 | 0/23 (0%) | 0 | 0/22 (0%) | 0 |
| Infections and infestations | ||||||||
| Bacterial infection | 0/23 (0%) | 0 | 0/22 (0%) | 0 | 0/23 (0%) | 0 | 1/22 (4.5%) | 1 |
| Infective spondylitis | 0/23 (0%) | 0 | 1/22 (4.5%) | 1 | 0/23 (0%) | 0 | 0/22 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Diabetes mellitus | 1/23 (4.3%) | 1 | 0/22 (0%) | 0 | 0/23 (0%) | 0 | 0/22 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Renal failure acute | 0/23 (0%) | 0 | 0/22 (0%) | 0 | 0/23 (0%) | 0 | 1/22 (4.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||
| Vaniprevir 200 mg + Peg-IFN + Ribavirin | Vaniprevir 600 mg + Peg-IFN + Ribavirin | Vaniprevir 1200 mg + Peg-IFN + Ribavirin | Placebo + Peg-IFN + Ribavirin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 23/23 (100%) | 22/22 (100%) | 23/23 (100%) | 22/22 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 2/23 (8.7%) | 2 | 4/22 (18.2%) | 4 | 3/23 (13%) | 3 | 3/22 (13.6%) | 3 |
| Leukopenia | 3/23 (13%) | 3 | 4/22 (18.2%) | 4 | 6/23 (26.1%) | 6 | 6/22 (27.3%) | 6 |
| Neutropenia | 3/23 (13%) | 3 | 1/22 (4.5%) | 1 | 5/23 (21.7%) | 5 | 6/22 (27.3%) | 6 |
| Thrombocytopenia | 1/23 (4.3%) | 1 | 6/22 (27.3%) | 7 | 3/23 (13%) | 3 | 3/22 (13.6%) | 4 |
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 2/23 (8.7%) | 2 | 1/22 (4.5%) | 1 | 3/23 (13%) | 3 | 2/22 (9.1%) | 2 |
| Abdominal pain upper | 2/23 (8.7%) | 2 | 0/22 (0%) | 0 | 1/23 (4.3%) | 1 | 1/22 (4.5%) | 1 |
| Constipation | 1/23 (4.3%) | 1 | 0/22 (0%) | 0 | 4/23 (17.4%) | 4 | 0/22 (0%) | 0 |
| Diarrhoea | 3/23 (13%) | 3 | 3/22 (13.6%) | 3 | 9/23 (39.1%) | 9 | 3/22 (13.6%) | 3 |
| Dyspepsia | 2/23 (8.7%) | 2 | 2/22 (9.1%) | 2 | 4/23 (17.4%) | 4 | 2/22 (9.1%) | 2 |
| Epigastric discomfort | 1/23 (4.3%) | 1 | 2/22 (9.1%) | 2 | 1/23 (4.3%) | 1 | 2/22 (9.1%) | 2 |
| Gastritis | 0/23 (0%) | 0 | 2/22 (9.1%) | 2 | 0/23 (0%) | 0 | 1/22 (4.5%) | 1 |
| Nausea | 6/23 (26.1%) | 6 | 1/22 (4.5%) | 1 | 9/23 (39.1%) | 9 | 4/22 (18.2%) | 4 |
| Periodontitis | 2/23 (8.7%) | 2 | 1/22 (4.5%) | 1 | 0/23 (0%) | 0 | 0/22 (0%) | 0 |
| Vomiting | 0/23 (0%) | 0 | 0/22 (0%) | 0 | 6/23 (26.1%) | 7 | 0/22 (0%) | 0 |
| General disorders | ||||||||
| Fatigue | 7/23 (30.4%) | 7 | 2/22 (9.1%) | 2 | 6/23 (26.1%) | 6 | 4/22 (18.2%) | 5 |
| Feeling hot | 3/23 (13%) | 3 | 0/22 (0%) | 0 | 0/23 (0%) | 0 | 0/22 (0%) | 0 |
| Influenza like illness | 0/23 (0%) | 0 | 1/22 (4.5%) | 1 | 1/23 (4.3%) | 1 | 3/22 (13.6%) | 3 |
| Malaise | 2/23 (8.7%) | 2 | 3/22 (13.6%) | 3 | 1/23 (4.3%) | 1 | 5/22 (22.7%) | 5 |
| Pyrexia | 12/23 (52.2%) | 13 | 15/22 (68.2%) | 15 | 9/23 (39.1%) | 10 | 12/22 (54.5%) | 15 |
| Infections and infestations | ||||||||
| Nasopharyngitis | 0/23 (0%) | 0 | 2/22 (9.1%) | 2 | 2/23 (8.7%) | 2 | 1/22 (4.5%) | 1 |
| Investigations | ||||||||
| Bilirubin conjugated increased | 1/23 (4.3%) | 1 | 0/22 (0%) | 0 | 2/23 (8.7%) | 2 | 1/22 (4.5%) | 1 |
| Blood creatinine increased | 0/23 (0%) | 0 | 0/22 (0%) | 0 | 2/23 (8.7%) | 2 | 1/22 (4.5%) | 1 |
| Blood potassium decreased | 0/23 (0%) | 0 | 2/22 (9.1%) | 2 | 1/23 (4.3%) | 1 | 1/22 (4.5%) | 1 |
| Eosinophil count decreased | 3/23 (13%) | 3 | 3/22 (13.6%) | 3 | 3/23 (13%) | 3 | 6/22 (27.3%) | 6 |
| Haematocrit decreased | 2/23 (8.7%) | 2 | 3/22 (13.6%) | 3 | 2/23 (8.7%) | 2 | 3/22 (13.6%) | 3 |
| Haemoglobin decreased | 9/23 (39.1%) | 9 | 7/22 (31.8%) | 7 | 10/23 (43.5%) | 10 | 8/22 (36.4%) | 8 |
| Monocyte count increased | 3/23 (13%) | 4 | 2/22 (9.1%) | 3 | 0/23 (0%) | 0 | 0/22 (0%) | 0 |
| Neutrophil count decreased | 7/23 (30.4%) | 7 | 9/22 (40.9%) | 9 | 11/23 (47.8%) | 13 | 7/22 (31.8%) | 7 |
| Platelet count decreased | 12/23 (52.2%) | 12 | 11/22 (50%) | 13 | 9/23 (39.1%) | 10 | 9/22 (40.9%) | 9 |
| White blood cell count decreased | 15/23 (65.2%) | 15 | 15/22 (68.2%) | 15 | 15/23 (65.2%) | 15 | 10/22 (45.5%) | 10 |
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 3/23 (13%) | 3 | 3/22 (13.6%) | 3 | 5/23 (21.7%) | 5 | 4/22 (18.2%) | 4 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 6/23 (26.1%) | 7 | 1/22 (4.5%) | 1 | 4/23 (17.4%) | 4 | 2/22 (9.1%) | 2 |
| Back pain | 3/23 (13%) | 3 | 0/22 (0%) | 0 | 2/23 (8.7%) | 2 | 0/22 (0%) | 0 |
| Musculoskeletal stiffness | 3/23 (13%) | 3 | 1/22 (4.5%) | 1 | 0/23 (0%) | 0 | 0/22 (0%) | 0 |
| Myalgia | 2/23 (8.7%) | 2 | 2/22 (9.1%) | 2 | 2/23 (8.7%) | 2 | 0/22 (0%) | 0 |
| Nervous system disorders | ||||||||
| Dizziness | 1/23 (4.3%) | 1 | 0/22 (0%) | 0 | 2/23 (8.7%) | 2 | 0/22 (0%) | 0 |
| Dysgeusia | 2/23 (8.7%) | 2 | 2/22 (9.1%) | 2 | 1/23 (4.3%) | 1 | 1/22 (4.5%) | 1 |
| Headache | 8/23 (34.8%) | 12 | 2/22 (9.1%) | 2 | 9/23 (39.1%) | 10 | 3/22 (13.6%) | 3 |
| Psychiatric disorders | ||||||||
| Insomnia | 1/23 (4.3%) | 1 | 2/22 (9.1%) | 2 | 2/23 (8.7%) | 2 | 1/22 (4.5%) | 1 |
| Renal and urinary disorders | ||||||||
| Pollakiuria | 1/23 (4.3%) | 1 | 0/22 (0%) | 0 | 0/23 (0%) | 0 | 2/22 (9.1%) | 2 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 1/23 (4.3%) | 1 | 4/22 (18.2%) | 4 | 3/23 (13%) | 3 | 2/22 (9.1%) | 2 |
| Dysphonia | 0/23 (0%) | 0 | 0/22 (0%) | 0 | 2/23 (8.7%) | 2 | 0/22 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Eczema | 3/23 (13%) | 3 | 1/22 (4.5%) | 1 | 1/23 (4.3%) | 1 | 1/22 (4.5%) | 1 |
| Pruritus | 1/23 (4.3%) | 1 | 3/22 (13.6%) | 3 | 3/23 (13%) | 3 | 5/22 (22.7%) | 5 |
| Rash | 4/23 (17.4%) | 4 | 3/22 (13.6%) | 3 | 2/23 (8.7%) | 2 | 1/22 (4.5%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT00880763
Other Study ID Numbers:
- 7009-016
- 2009_576
First Posted:
Apr 14, 2009
Last Update Posted:
Oct 9, 2018
Last Verified:
Sep 1, 2018