QUEST-2: An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Participants
Sponsor
Janssen R&D Ireland (Industry)
Overall Status
Completed
CT.gov ID
NCT01290679
Collaborator
(none)
393
62
2
23.1
6.3
0.3
Study Details
Study Description
Brief Summary
The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in participants who are infected with genotype 1 hepatitis C virus who have never received treatment before. Participants will also receive peginterferon alfa-2a or peginterferon alfa-2b and ribavirin as part of their treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a randomized, double-blind (neither physician or participant knows the name of the assigned drug), placebo-controlled study of TMC435 in participants who are infected with genotype 1 hepatitis C virus who have never received treatment for this before. Participants in this study will also receive two other drugs for their infection (either peginterferon alfa-2a (Pegasys®) and ribavirin (Copegus®) or peginterferon alfa-2b (PegIntron®) and ribavirin (Rebetol®). The purpose of the study is to investigate if TMC435 is superior to placebo in reducing hepatitis C virus to an undetectable level 24 weeks after the end of treatment. For the first 12 weeks, participants will take TMC435 or placebo, plus peginterferon and ribavirin. For the next 12 weeks, participants will take peginterferon and ribavirin only. After that, some participants will continue to take peginterferon and ribavirin for up to 24 additional weeks. Other participants will stop taking peginterferon and ribavirin. The study doctor will inform each participant about how to take their study medication and when they should stop taking it. After a participant stops taking study medication, they will continue to come to the doctor's office for study visits until a total of 72 weeks after they enroll in the study. The total duration of the study is 78 weeks (including screening). Participants will be monitored for safety throughout the study. Study assessments at each study visit may include but are not limited to: blood and urine collection for testing, electrocardiogram (ECG) assessments (a measurement of the electrical activity of your heart), participant questionnaires, and physical examinations. TMC435 will be taken as an oral capsule of 150 mg once per day. Peginterferon (Pegasys ®) will be given as an injection of 180 µg once each week. Peginterferon (PegIntron®) will be given as an injection once each week and the dose will depend on your body weight. Ribavirin will be taken as a tablet (Copegus ®) or a capsule (Rebetol ®) twice each day and the dose will depend on your body weight.
Study Design
Study Type:
Interventional
Actual Enrollment
:
393 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 Versus Placebo as Part of a Treatment Regimen Including Peginterferon α-2a (Pegasys®) and Ribavirin (Copegus®) or Peginterferon α-2b (PegIntron®) and Ribavirin (Rebetol®) in Treatment-naïve, Genotype 1, Hepatitis C-infected Subjects
Study Start Date
:
Mar 1, 2011
Actual Primary Completion Date
:
Feb 1, 2013
Actual Study Completion Date
:
Feb 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TMC435 TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron) (PegIFN alpha-2a/b) and ribavirin (Copegus or Rebetol) for 24 or 48 weeks |
Drug: TMC435
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a or peginterferon alfa-2b and ribavirin for 24 or 48 weeks
Drug: Peginterferon alpha-2a or Peginterferon alpha-2b (PegIFNα-2a/b)
One subcutaneous (under the skin) injection of PegIFNα-2a (containing 0.5 mL solution with 180 mcg PegIFNα-2a) OR PegIFNα-2b (0.5 mL from a pre-filled pen) once weekly for up to 48 weeks.
Other Names:
Drug: Ribavirin (RBV)
200-mg tablets of ribavirin (Copegus or Rebetol) (body-weight adjusted dose) taken orally (by mouth) twice daily for up to 48 weeks.
Other Names:
|
| Placebo Comparator: Placebo Placebo 150 mg capsule once daily for 12 weeks in addition peginterferon alfa-2a (Pegasys) or peginterferon alfa-2b (PegIntron) (PegIFN alpha-2a/b) and ribavirin (Copegus or Rebetol) for 48 weeks |
Drug: Placebo
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a or peginterferon alfa-2b and ribavirin for 48 weeks
Drug: Peginterferon alpha-2a or Peginterferon alpha-2b (PegIFNα-2a/b)
One subcutaneous (under the skin) injection of PegIFNα-2a (containing 0.5 mL solution with 180 mcg PegIFNα-2a) OR PegIFNα-2b (0.5 mL from a pre-filled pen) once weekly for up to 48 weeks.
Other Names:
Drug: Ribavirin (RBV)
200-mg tablets of ribavirin (Copegus or Rebetol) (body-weight adjusted dose) taken orally (by mouth) twice daily for up to 48 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) [Week 36 or Week 60]
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.
Secondary Outcome Measures
- The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) [Week 72]
The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72.
- The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) [Week 48 or Week 72]
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 24 weeks after planned end of treatment.
- The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4) [Week 28 or Week 52]
The table below shows the percentage of participants in each treatment group who achieved a SVR4, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 4 weeks after planned end of treatment.
- Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) [Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48]
The table below shows changes from baseline in log10 HCV RNA.
- Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) [Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48]
The table below shows actual values of log10 HCV RNA levels.
- Percentage of Participants With On-treatment Virologic Response at All Time Points [Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42]
The table below shows the percentage of participants with Hepatitis C Virus (HCV) ribonucleic acid (RNA) plasma levels below the limit of detection (ie, <25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA <100 IU/mL, the percentage of HCV-Infected participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA.
- The Percentage of Participants Achieving a Rapid Virologic Response (RVR) [Week 4]
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment.
- The Percentage of Participants Achieving a Early Virologic Response (EVR) [Week 12]
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12.
- The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) [Week 12]
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12.
- The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR) [Weeks 4 and 12]
The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12.
- The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4 [Week 4]
The table below shows the percentage of participants in each treatment group with <1 log10 HCV RNA decrease at Week 4.
- Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4 [Week 4]
The table below shows the percentage of participants in each treatment group with HCV RNA levels >1000 IU/mL at Week 4.
- Percentage of Participants With Null Response [Week 12]
The table below shows the percentage of participants with null response, defined as <2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline.
- Percentage of Participants With Partial Response [Week 12]
The table below shows the percentage of participants with partial response, defined as =>2 log10 reduction in Hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment.
- Percentage of Participants With Viral Breakthrough [Up to Week 48]
The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable).
- Percentage of Participants With Viral Relapse [Up to Week 72]
The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (<25 IU/mL undetectable) at the end of treatment.
- Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule [Week 24]
The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus [HCV] ribonucleic acid [RNA] levels <25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks.
- Percentage of Participants With On-treatment Failure [Week 48]
The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment.
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable [Up to Week 48]
The table below shows the median time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable.
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable [Up to Week 48]
The table below shows the median time in days to reach HCV RNA levels <25 IU/mL undetectable.
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL [Up to Week 48]
The table below shows the median time in days to reach HCV RNA levels <100 IU/mL.
- Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL [Up to Week 48]
The table below shows the median time in days to reach HCV RNA levels <1000 IU/mL.
- The Percentage of Participants With Viral Breakthrough at Different Time Points [Up to Week 48]
The table below shows the percentage of participants at different time points with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable).
- Time From End-of-treatment to Viral Relapse [Up to Week 72]
The table below shows the mean number of days to viral relapse, defined as participants having confirmed detectable plasma level of Hepatitis C Virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (<25 IU/mL undetectable) at the end of treatment.
- The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) [Up to Week 48]
The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 164 of 257 participants in the TMC435 treatment group and 79 of 134 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range.
- Median Time to Normalization of Alanine Aminotransferase (ALT) Levels [Up to Week 48]
The table below shows the median time in weeks to normalization of ALT levels.
- Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) [At protocol-specified time points from the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12]
The table below shows the mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435.
- Plasma Concentration of TMC435: Predose Plasma Concentration (C0h) [Blood samples tested were taken before administration of TMC435 and at 2 random time points after dosing (taken atleast 2 hours apart from each other) at Week 2, 4, 8, and 12]
The table below shows the mean (standard deviation) of C0h values of TMC435. NOTE: the timing of collection of blood samples post-dose for analysis at Week 2, 4, 8, and 12 was not specifed; only the interval was between blood samples was specified (ie, 2 samples collected 2 hours apart at Week 2, 4, 8, and 12).
- Plasma Concentration of TMC435: Systemic Clearance (CL) [At protocol-specified time points at Weeks 2, 4, 8, and 12]
The table below shows the mean (standard deviation) of CL values of TMC435. NOTE: the pre-dose CL values taken at Weeks, 2, 4, 8, and 12 were averaged and then the mean values from all participants were averaged to provide the final value reported below.
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores [Baseline to Week 60 and Week 72]
Study participants completed FSS questionnaires during study visits before treatment and throughout follow-up to rate the severity and impact of fatigue experienced in the preceding 2 weeks. FSS total scores are the average of nine questions with a range from 1 [no fatigue] to 7 [worst fatigue]; the possible score range from baseline to Week 60 would be 60-420 and to Week 72 would be 72-504. The average FSS total score from baseline to Week 60 and to Week 72 was calculated for each participant and then the average of those values were calculated to show the average FSS total score for each treatment group. The null hypothesis was that there would be no difference between the treatment arms in the FSS total score. The Table below shows the lease squares (LS) mean estimates of the area under the curve (AUC) at Week 72 (as well as at Week 60) and the statistical comparison between treatment groups.
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Due to Hepatitis C Virus (HCV) Infection and Its Treatment [Baseline to Week 60 and Week 72]
Impairment in overall work productivity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire completed by participants throughout the study. WPAI Overall Productivity Scores ranged from 0% to 100% (higher WPAI scores indicated greater impairment in productivity). The average WPAI score from baseline to Week 72 was calculated for each participant and then the average of those values were calculated to show the average WPAI score for each treatment group. The null hypothesis was there is no statistically significant difference between the treatment groups in the AUC for the change from baseline to Week 72 (AUC72) in WPAI Productivity Scores. The Table below shows WPAI Productivity Scores at Week 72 (as well as at Week 60) from the model used to calculate the AUC and the statistical comparison between treatment groups.
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activities Due to Hepatitis C Virus (HCV) Infection and Its Treatment [Baseline to Week 60 and Week 72]
Impairment in daily activity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire, Question 6. The possible impairment in WPAI daily activity score range from baseline to Week 60 was 0-6000 and to Week 72 was 0-7200, with the higher scores indicating more impairment in daily activities. The average WPAI impairment in daily activity score from baseline to Week 72 was calculated for each participant and then the average of those values were calculated to show the average WPAI impairment in daily activity score for each treatment group. The null hypothesis was there is no statistically significant difference between the treatment arms in the AUC for the change from baseline to Week 72 (AUC72) in WPAI impairment in daily activity scores. The Table below shows the WPAI Impairment in daily activity scores at Week 72 (as well as at Week 60) and the statistical analysis between treatment groups.
- Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Time Missed From Work Due to Hepatitis C Virus (HCV) Infection and Its Treatment [Baseline to Week 60 and Week 72]
Hours missed from work because of HCV infection or its treatment was assessed by measuring the change from baseline in the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire Absenteeism score (time missed from work). The possible WPAI WPAI absenteeism score range from baseline to Week 60 was 0-6000 and to Week 72 was 0-7200, with the higher scores indicating more impairment in WPAI absenteeism. The average WPAI absenteeism score from baseline to Week 60/72 was calculated for each participant and then the average of those values calculated for each treatment group. The area under the curve (AUC60/AUC72) over time from baseline to Week 60/72 was derived from a piecewise-linear model allowing the slopes to change at Week 4, 12, 24, 36, 48 and 60. The null hypothesis was there is no statistically significant difference between the treatment arms in the area under the curve (AUC) from baseline to Week 72 (AUC72) in WPAI absenteeism score.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Genotype 1 hepatitis C infection (confirmed at screening)
-
Participant has not received any prior treatment for hepatitis C
-
Participant must have had a liver biopsy within 3 years before screening (or between the screening and baseline visit) showing chronic hepatitis C infection
-
Must agree to use 2 forms of effective contraception throughout study (both males and females)
Exclusion Criteria:
-
Infection with HIV or non genotype 1 hepatitis C
-
Liver disease not related to hepatitic C infection
-
Hepatic decompensation
-
Significant laboratory abnormalities or other active diseases
-
Pregnant or planning to become pregnant
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Los Angeles | California | United States | ||
| 2 | Jacksonville | Florida | United States | ||
| 3 | Orlando | Florida | United States | ||
| 4 | Atlanta | Georgia | United States | ||
| 5 | Crestview Hills | Kentucky | United States | ||
| 6 | New Orleans | Louisiana | United States | ||
| 7 | Saint Paul | Minnesota | United States | ||
| 8 | Germantown | Tennessee | United States | ||
| 9 | Houston | Texas | United States | ||
| 10 | San Antonio | Texas | United States | ||
| 11 | Falls Church | Virginia | United States | ||
| 12 | Buenos Aires | Argentina | |||
| 13 | Rosario, Santa Fe | Argentina | |||
| 14 | Wien | Austria | |||
| 15 | Antwerpen | Belgium | |||
| 16 | Brugge | Belgium | |||
| 17 | Brussels | Belgium | |||
| 18 | Brussel | Belgium | |||
| 19 | Gent | Belgium | |||
| 20 | Leuven | Belgium | |||
| 21 | Salvador | Brazil | |||
| 22 | Sao Paulo | Brazil | |||
| 23 | São Paulo | Brazil | |||
| 24 | Plovdiv | Bulgaria | |||
| 25 | Sofia | Bulgaria | |||
| 26 | Clichy | France | |||
| 27 | Creteil N/A | France | |||
| 28 | Nice N/A | France | |||
| 29 | Paris | France | |||
| 30 | Vandoeuvre Les Nancy | France | |||
| 31 | Berlin | Germany | |||
| 32 | Düsseldorf | Germany | |||
| 33 | Freiburg | Germany | |||
| 34 | Halle (Saale) | Germany | |||
| 35 | Hannover | Germany | |||
| 36 | Kiel | Germany | |||
| 37 | Leipzig | Germany | |||
| 38 | Munchen | Germany | |||
| 39 | Münster | Germany | |||
| 40 | Ulm | Germany | |||
| 41 | Amsterdam Zuidoost | Netherlands | |||
| 42 | Leiden | Netherlands | |||
| 43 | Bialystok | Poland | |||
| 44 | Bydgoszcz | Poland | |||
| 45 | Chorzow | Poland | |||
| 46 | Czeladz | Poland | |||
| 47 | Kielce | Poland | |||
| 48 | Krakow | Poland | |||
| 49 | Warszawa | Poland | |||
| 50 | Coimbra | Portugal | |||
| 51 | Lisboa | Portugal | |||
| 52 | Porto | Portugal | |||
| 53 | Santurce | Puerto Rico | |||
| 54 | Bratislava | Slovakia | |||
| 55 | Martin | Slovakia | |||
| 56 | Barcelona | Spain | |||
| 57 | Madrid | Spain | |||
| 58 | Sevilla N/A | Spain | |||
| 59 | Valencia | Spain | |||
| 60 | Ankara | Turkey | |||
| 61 | Istanbul | Turkey | |||
| 62 | Izmir | Turkey |
Sponsors and Collaborators
- Janssen R&D Ireland
Investigators
- Study Director: Janssen R&D Ireland Clinical Trial, Janssen R&D Ireland
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT01290679
Other Study ID Numbers:
- CR017380
- TMC435-TiDP16-C216
- 2010-021174-11
First Posted:
Feb 7, 2011
Last Update Posted:
Jun 13, 2014
Last Verified:
Jun 1, 2014
Keywords provided by Janssen R&D Ireland
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted from 18 January 2011 to 5 February 2013. The study was conducted at 76 sites in 14 countries. |
|---|---|
| Pre-assignment Detail | 393 participants were randomly allocated to the 2 treatment arms. 391 participants received at least 1 dose of study medication and were included in the intent-to-treat analysis set. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Period Title: Overall Study | ||
| STARTED | 257 | 134 |
| COMPLETED | 241 | 113 |
| NOT COMPLETED | 16 | 21 |
Baseline Characteristics
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 | Total |
|---|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). | Total of all reporting groups |
| Overall Participants | 257 | 134 | 391 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
46
|
47
|
47
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
117
45.5%
|
57
42.5%
|
174
44.5%
|
| Male |
140
54.5%
|
77
57.5%
|
217
55.5%
|
Outcome Measures
| Title | The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) |
|---|---|
| Description | The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment. |
| Time Frame | Week 36 or Week 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
81.3
31.6%
|
50.0
37.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | The null hypothesis is there is no difference in proportions of SVR12 between the treatment groups. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in proportions of SVR12 |
| Estimated Value | 32.2 | |
| Confidence Interval |
(2-Sided) 95% 23.3 to 41.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) |
|---|---|
| Description | The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72. |
| Time Frame | Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
78.6
30.6%
|
50.0
37.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | The null hypothesis is there is no difference in proportions of SVRW72 between the treatment groups. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in proportions of SVRW72 |
| Estimated Value | 29.3 | |
| Confidence Interval |
(2-Sided) 95% 20.2 to 38.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) |
|---|---|
| Description | The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 24 weeks after planned end of treatment. |
| Time Frame | Week 48 or Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
80.5
31.3%
|
50.0
37.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | The null hypothesis is there is no difference in proportions of SVR24 between the treatment groups. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in proportions of SVR24 |
| Estimated Value | 31.5 | |
| Confidence Interval |
(2-Sided) 95% 22.5 to 40.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4) |
|---|---|
| Description | The table below shows the percentage of participants in each treatment group who achieved a SVR4, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 4 weeks after planned end of treatment. |
| Time Frame | Week 28 or Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
84.8
33%
|
53.0
39.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | The null hypothesis is there is no difference in proportions of SVR4 between the treatment groups. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in proportions of SVR4 |
| Estimated Value | 32.3 | |
| Confidence Interval |
(2-Sided) 95% 23.5 to 41.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
|---|---|
| Description | The table below shows changes from baseline in log10 HCV RNA. |
| Time Frame | Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Day 3 |
-3.60
(0.045)
|
-1.22
(0.075)
|
| Week 1 |
-4.52
(0.043)
|
-1.21
(0.094)
|
| Week 4 |
-5.28
(0.046)
|
-2.72
(0.138)
|
| Week 12 |
-5.34
(0.053)
|
-4.21
(0.129)
|
| Week 24 |
-5.27
(0.062)
|
-4.93
(0.114)
|
| Week 48 |
-5.83
(0.074)
|
-5.28
(0.084)
|
| Title | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) |
|---|---|
| Description | The table below shows actual values of log10 HCV RNA levels. |
| Time Frame | Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Day 3 |
2.777
(0.050)
|
5.165
(0.107)
|
| Week 1 |
1.852
(0.400)
|
5.171
(0.129)
|
| Week 4 |
1.093
(0.027)
|
3.657
(0.162)
|
| Week 12 |
1.027
(0.034)
|
2.157
(0.141)
|
| Week 24 |
1.094
(0.049)
|
1.388
(0.106)
|
| Week 48 |
1.015
(0.061)
|
0.960
(0.005)
|
| Title | Percentage of Participants With On-treatment Virologic Response at All Time Points |
|---|---|
| Description | The table below shows the percentage of participants with Hepatitis C Virus (HCV) ribonucleic acid (RNA) plasma levels below the limit of detection (ie, <25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA <100 IU/mL, the percentage of HCV-Infected participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA. |
| Time Frame | Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Day 3:<25 IU/mL undetectable |
0.4
0.2%
|
0
0%
|
| Week 1:<25 IU/mL undetectable |
6.3
2.5%
|
1.5
1.1%
|
| Week 2:<25 IU/mL undetectable |
31.7
12.3%
|
3.8
2.8%
|
| Week 8:<25 IU/mL undetectable |
93.7
36.5%
|
31.3
23.4%
|
| Week 16:<25 IU/mL undetectable |
96.3
37.5%
|
65.5
48.9%
|
| Week 20:<25 IU/mL undetectable |
95.9
37.3%
|
68.2
50.9%
|
| Week 28:<25 IU/mL undetectable |
66.7
26%
|
88.0
65.7%
|
| Week 36:<25 IU/mL undetectable |
100.0
38.9%
|
95.3
71.1%
|
| Week 42:<25 IU/mL undetectable |
100.0
38.9%
|
95.0
70.9%
|
| Day 3:<25 IU/mL detectable or undetectable |
4.7
1.8%
|
0
0%
|
| Week 1:<25 IU/mL detectable or undetectable |
37.0
14.4%
|
2.3
1.7%
|
| Week 2:<25 IU/mL detectable or undetectable |
80.7
31.4%
|
12.0
9%
|
| Week 8:<25 IU/mL detectable or undetectable |
98.0
38.1%
|
45.0
33.6%
|
| Week 16:<25 IU/mL detectable or undetectable |
98.0
38.1%
|
73.5
54.9%
|
| Week 20:<25 IU/mL detectable or undetectable |
97.1
37.8%
|
79.1
59%
|
| Week 28:<25 IU/mL detectable or undetectable |
77.8
30.3%
|
97.8
73%
|
| Week 36:<25 IU/mL detectable or undetectable |
100.0
38.9%
|
98.8
73.7%
|
| Week 42:<25 IU/mL detectable or undetectable |
100.0
38.9%
|
100.0
74.6%
|
| Day 3:<100 IU/mL |
15.3
6%
|
1.5
1.1%
|
| Week 1:<100 IU/mL |
65.7
25.6%
|
6.0
4.5%
|
| Week 2:<100 IU/mL |
92.0
35.8%
|
14.3
10.7%
|
| Week 8:<100 IU/mL |
98.8
38.4%
|
50.4
37.6%
|
| Week 16:<100 IU/mL |
98.8
38.4%
|
77.0
57.5%
|
| Week 20:<100 IU/mL |
98.0
38.1%
|
83.6
62.4%
|
| Week 28:<100 IU/mL |
77.8
30.3%
|
97.8
73%
|
| Week 36:<100 IU/mL |
100.0
38.9%
|
98.8
73.7%
|
| Week 42:<100 IU/mL |
100.0
38.9%
|
100.0
74.6%
|
| Day 3:> or = 2 log 10 change from baseline |
96.9
37.7%
|
20.8
15.5%
|
| Week 1:> or =2 log 10 change from baseline |
99.6
38.8%
|
24.1
18%
|
| Week 2:> or =2 log 10 change from baseline |
99.6
38.8%
|
39.8
29.7%
|
| Week 8:> or =2 log 10 change from baseline |
99.6
38.8%
|
80.2
59.9%
|
| Week 16:> or =2 log 10 change from baseline |
99.2
38.6%
|
97.3
72.6%
|
| Week 20:> or =2 log 10 change from baseline |
98.8
38.4%
|
93.6
69.9%
|
| Week 28:> or =2 log 10 change from baseline |
88.9
34.6%
|
100.0
74.6%
|
| Week 36:> or =2 log 10 change from baseline |
100.0
38.9%
|
98.8
73.7%
|
| Week 42:> or =2 log 10 change from baseline |
100.0
38.9%
|
100.0
74.6%
|
| Title | The Percentage of Participants Achieving a Rapid Virologic Response (RVR) |
|---|---|
| Description | The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
79.2
30.8%
|
12.8
9.6%
|
| Title | The Percentage of Participants Achieving a Early Virologic Response (EVR) |
|---|---|
| Description | The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
98.8
38.4%
|
89.8
67%
|
| Title | The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) |
|---|---|
| Description | The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
96.8
37.7%
|
44.9
33.5%
|
| Title | The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR) |
|---|---|
| Description | The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12. |
| Time Frame | Weeks 4 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
78.3
30.5%
|
13.4
10%
|
| Title | The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4 |
|---|---|
| Description | The table below shows the percentage of participants in each treatment group with <1 log10 HCV RNA decrease at Week 4. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
0.4
0.2%
|
17.3
12.9%
|
| Title | Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4 |
|---|---|
| Description | The table below shows the percentage of participants in each treatment group with HCV RNA levels >1000 IU/mL at Week 4. |
| Time Frame | Week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
1.2
0.5%
|
61.2
45.7%
|
| Title | Percentage of Participants With Null Response |
|---|---|
| Description | The table below shows the percentage of participants with null response, defined as <2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
1.2
0.5%
|
10.2
7.6%
|
| Title | Percentage of Participants With Partial Response |
|---|---|
| Description | The table below shows the percentage of participants with partial response, defined as =>2 log10 reduction in Hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
0.4
0.2%
|
17.3
12.9%
|
| Title | Percentage of Participants With Viral Breakthrough |
|---|---|
| Description | The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable). |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
4.7
1.8%
|
10.4
7.8%
|
| Title | Percentage of Participants With Viral Relapse |
|---|---|
| Description | The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (<25 IU/mL undetectable) at the end of treatment. |
| Time Frame | Up to Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
12.3
4.8%
|
23.9
17.8%
|
| Title | Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule |
|---|---|
| Description | The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus [HCV] ribonucleic acid [RNA] levels <25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
89.5
34.8%
|
NA
NaN
|
| Title | Percentage of Participants With On-treatment Failure |
|---|---|
| Description | The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment. |
| Time Frame | Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Number [Percentage of participants] |
7.0
2.7%
|
32.1
24%
|
| Title | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable |
|---|---|
| Description | The table below shows the median time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Median (95% Confidence Interval) [Days] |
14
|
85
|
| Title | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable |
|---|---|
| Description | The table below shows the median time in days to reach HCV RNA levels <25 IU/mL undetectable. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Median (95% Confidence Interval) [Days] |
29
|
113
|
| Title | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL |
|---|---|
| Description | The table below shows the median time in days to reach HCV RNA levels <100 IU/mL. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Median (95% Confidence Interval) [Days] |
8
|
71
|
| Title | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL |
|---|---|
| Description | The table below shows the median time in days to reach HCV RNA levels <1000 IU/mL. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Median (95% Confidence Interval) [Days] |
4
|
57
|
| Title | The Percentage of Participants With Viral Breakthrough at Different Time Points |
|---|---|
| Description | The table below shows the percentage of participants at different time points with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable). |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| < 12 Weeks |
1.2
0.5%
|
3.7
2.8%
|
| Week 12 - Week 24 |
3.3
1.3%
|
6.4
4.8%
|
| > Week 24 |
12.5
4.9%
|
2.1
1.6%
|
| Title | Time From End-of-treatment to Viral Relapse |
|---|---|
| Description | The table below shows the mean number of days to viral relapse, defined as participants having confirmed detectable plasma level of Hepatitis C Virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (<25 IU/mL undetectable) at the end of treatment. |
| Time Frame | Up to Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Mean (Standard Error) [Days] |
229.77
(4.29)
|
77.74
(2.34)
|
| Title | The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) |
|---|---|
| Description | The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 164 of 257 participants in the TMC435 treatment group and 79 of 134 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 169 | 79 |
| Number [Percentage of participants] |
79.9
31.1%
|
81.0
60.4%
|
| Title | Median Time to Normalization of Alanine Aminotransferase (ALT) Levels |
|---|---|
| Description | The table below shows the median time in weeks to normalization of ALT levels. |
| Time Frame | Up to Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 257 | 134 |
| Median (95% Confidence Interval) [Weeks] |
2.14
|
4.14
|
| Title | Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) |
|---|---|
| Description | The table below shows the mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435. |
| Time Frame | At protocol-specified time points from the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 |
|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). |
| Measure Participants | 255 |
| Mean (Standard Deviation) [ng*h/mL] |
56611
(66935.4)
|
| Title | Plasma Concentration of TMC435: Predose Plasma Concentration (C0h) |
|---|---|
| Description | The table below shows the mean (standard deviation) of C0h values of TMC435. NOTE: the timing of collection of blood samples post-dose for analysis at Week 2, 4, 8, and 12 was not specifed; only the interval was between blood samples was specified (ie, 2 samples collected 2 hours apart at Week 2, 4, 8, and 12). |
| Time Frame | Blood samples tested were taken before administration of TMC435 and at 2 random time points after dosing (taken atleast 2 hours apart from each other) at Week 2, 4, 8, and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 |
|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). |
| Measure Participants | 255 |
| Mean (Standard Deviation) [ng/mL] |
1902
(2781.1)
|
| Title | Plasma Concentration of TMC435: Systemic Clearance (CL) |
|---|---|
| Description | The table below shows the mean (standard deviation) of CL values of TMC435. NOTE: the pre-dose CL values taken at Weeks, 2, 4, 8, and 12 were averaged and then the mean values from all participants were averaged to provide the final value reported below. |
| Time Frame | At protocol-specified time points at Weeks 2, 4, 8, and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 |
|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). |
| Measure Participants | 255 |
| Mean (Standard Deviation) [L/h] |
5.23
(3.767)
|
| Title | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores |
|---|---|
| Description | Study participants completed FSS questionnaires during study visits before treatment and throughout follow-up to rate the severity and impact of fatigue experienced in the preceding 2 weeks. FSS total scores are the average of nine questions with a range from 1 [no fatigue] to 7 [worst fatigue]; the possible score range from baseline to Week 60 would be 60-420 and to Week 72 would be 72-504. The average FSS total score from baseline to Week 60 and to Week 72 was calculated for each participant and then the average of those values were calculated to show the average FSS total score for each treatment group. The null hypothesis was that there would be no difference between the treatment arms in the FSS total score. The Table below shows the lease squares (LS) mean estimates of the area under the curve (AUC) at Week 72 (as well as at Week 60) and the statistical comparison between treatment groups. |
| Time Frame | Baseline to Week 60 and Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 256 | 133 |
| Week 60 |
208.418
|
225.194
|
| Week 72 |
240.695
|
259.532
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | Fatigue Severity Score AUC60 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | ||
| Method | Piecewise Linear Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean differences |
| Estimated Value | -16.776 | |
| Confidence Interval |
(2-Sided) 95% -29.1502 to -4.4025 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 6.3081 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | Fatigue Severity Score AUC72 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | ||
| Method | Piecewise Linear Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean differences |
| Estimated Value | -18.837 | |
| Confidence Interval |
(2-Sided) 95% -33.4933 to -4.1801 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 7.4715 |
|
| Estimation Comments | ||
| Title | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Due to Hepatitis C Virus (HCV) Infection and Its Treatment |
|---|---|
| Description | Impairment in overall work productivity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire completed by participants throughout the study. WPAI Overall Productivity Scores ranged from 0% to 100% (higher WPAI scores indicated greater impairment in productivity). The average WPAI score from baseline to Week 72 was calculated for each participant and then the average of those values were calculated to show the average WPAI score for each treatment group. The null hypothesis was there is no statistically significant difference between the treatment groups in the AUC for the change from baseline to Week 72 (AUC72) in WPAI Productivity Scores. The Table below shows WPAI Productivity Scores at Week 72 (as well as at Week 60) from the model used to calculate the AUC and the statistical comparison between treatment groups. |
| Time Frame | Baseline to Week 60 and Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 256 | 133 |
| Week 60 |
1628.075
|
1910.235
|
| Week 72 |
1781.768
|
2106.131
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | Impairment in Work Productivity AUC60 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | ||
| Method | Piecewise Linear Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean differences |
| Estimated Value | -282.160 | |
| Confidence Interval |
(2-Sided) 95% -489.1252 to -75.1949 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 105.4927 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | Impairment in Work Productivity AUC72 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.009 |
| Comments | ||
| Method | Piecewise Linear Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean differences |
| Estimated Value | -324.363 | |
| Confidence Interval |
(2-Sided) 95% -567.7080 to -81.0182 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 124.0260 |
|
| Estimation Comments | ||
| Title | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activities Due to Hepatitis C Virus (HCV) Infection and Its Treatment |
|---|---|
| Description | Impairment in daily activity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire, Question 6. The possible impairment in WPAI daily activity score range from baseline to Week 60 was 0-6000 and to Week 72 was 0-7200, with the higher scores indicating more impairment in daily activities. The average WPAI impairment in daily activity score from baseline to Week 72 was calculated for each participant and then the average of those values were calculated to show the average WPAI impairment in daily activity score for each treatment group. The null hypothesis was there is no statistically significant difference between the treatment arms in the AUC for the change from baseline to Week 72 (AUC72) in WPAI impairment in daily activity scores. The Table below shows the WPAI Impairment in daily activity scores at Week 72 (as well as at Week 60) and the statistical analysis between treatment groups. |
| Time Frame | Baseline to Week 60 and Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 256 | 133 |
| Week 60 |
1580.635
|
1863.071
|
| Week 72 |
1727.079
|
2056.283
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | Impairment in Daily Activities AUC60 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.007 |
| Comments | ||
| Method | Piecewise linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Differences |
| Estimated Value | -282.436 | |
| Confidence Interval |
(2-Sided) 95% -488.4150 to -76.4566 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 104.9894 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | Impairment in Daily Activities AUC72 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.008 |
| Comments | ||
| Method | Piecewise Linear Model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean differences |
| Estimated Value | -329.204 | |
| Confidence Interval |
(2-Sided) 95% -571.3389 to -87.0695 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 123.4080 |
|
| Estimation Comments | ||
| Title | Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Time Missed From Work Due to Hepatitis C Virus (HCV) Infection and Its Treatment |
|---|---|
| Description | Hours missed from work because of HCV infection or its treatment was assessed by measuring the change from baseline in the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire Absenteeism score (time missed from work). The possible WPAI WPAI absenteeism score range from baseline to Week 60 was 0-6000 and to Week 72 was 0-7200, with the higher scores indicating more impairment in WPAI absenteeism. The average WPAI absenteeism score from baseline to Week 60/72 was calculated for each participant and then the average of those values calculated for each treatment group. The area under the curve (AUC60/AUC72) over time from baseline to Week 60/72 was derived from a piecewise-linear model allowing the slopes to change at Week 4, 12, 24, 36, 48 and 60. The null hypothesis was there is no statistically significant difference between the treatment arms in the area under the curve (AUC) from baseline to Week 72 (AUC72) in WPAI absenteeism score. |
| Time Frame | Baseline to Week 60 and Week 72 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. |
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 |
|---|---|---|
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). |
| Measure Participants | 182 | 89 |
| Week 60 |
653.642
|
840.495
|
| Week 72 |
698.223
|
886.425
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | Time Missed from Work AUC60 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.125 |
| Comments | ||
| Method | Piecewise linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean differences |
| Estimated Value | -186.852 | |
| Confidence Interval |
(2-Sided) 95% -425.4109 to 51.7059 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 121.4741 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48 |
|---|---|---|
| Comments | Time Missed from Work AUC72 | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.183 |
| Comments | ||
| Method | Piecewise linear model | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean differences |
| Estimated Value | -188.202 | |
| Confidence Interval |
(2-Sided) 95% -465.5070 to 89.1040 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 141.1702 |
|
| Estimation Comments | ||
Adverse Events
| Time Frame | 72 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 | ||
| Arm/Group Description | Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA < 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | Participants were given placebo (PBO) once daily plus peginterferon alpha-2a/b (PegIFN alpha-2a/b) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a/b (P) and RBV (R) until Week 48 (PR 48). | ||
All Cause Mortality |
||||
| TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/257 (6.2%) | 10/134 (7.5%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/257 (0.8%) | 1/134 (0.7%) | ||
| Pancytopenia | 0/257 (0%) | 1/134 (0.7%) | ||
| Cardiac disorders | ||||
| Angina unstable | 0/257 (0%) | 1/134 (0.7%) | ||
| Ear and labyrinth disorders | ||||
| Mixed deafness | 1/257 (0.4%) | 0/134 (0%) | ||
| Endocrine disorders | ||||
| Hyperthyroidism | 1/257 (0.4%) | 0/134 (0%) | ||
| Eye disorders | ||||
| Hyphaema | 1/257 (0.4%) | 0/134 (0%) | ||
| Visual impairment | 1/257 (0.4%) | 0/134 (0%) | ||
| Retinal ischaemia | 0/257 (0%) | 1/134 (0.7%) | ||
| Gastrointestinal disorders | ||||
| Enterocutaneous fistula | 1/257 (0.4%) | 0/134 (0%) | ||
| Pancreatitis acute | 0/257 (0%) | 1/134 (0.7%) | ||
| Vomiting | 0/257 (0%) | 1/134 (0.7%) | ||
| General disorders | ||||
| Death | 1/257 (0.4%) | 0/134 (0%) | ||
| Hepatobiliary disorders | ||||
| Autoimmune hepatitis | 1/257 (0.4%) | 0/134 (0%) | ||
| Cholecystitis acute | 0/257 (0%) | 1/134 (0.7%) | ||
| Infections and infestations | ||||
| Anal abscess | 1/257 (0.4%) | 0/134 (0%) | ||
| Lymphadenitis bacterial | 1/257 (0.4%) | 0/134 (0%) | ||
| Urinary tract infection | 1/257 (0.4%) | 0/134 (0%) | ||
| Respiratory tract infection viral | 0/257 (0%) | 1/134 (0.7%) | ||
| Viral infection | 0/257 (0%) | 1/134 (0.7%) | ||
| Injury, poisoning and procedural complications | ||||
| Meniscus lesion | 0/257 (0%) | 1/134 (0.7%) | ||
| Metabolism and nutrition disorders | ||||
| Fluid overload | 1/257 (0.4%) | 0/134 (0%) | ||
| Dehydration | 0/257 (0%) | 1/134 (0.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/257 (0.4%) | 0/134 (0%) | ||
| Muscle spasms | 1/257 (0.4%) | 0/134 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Colon cancer | 1/257 (0.4%) | 0/134 (0%) | ||
| Nervous system disorders | ||||
| Epilepsy | 1/257 (0.4%) | 0/134 (0%) | ||
| Memory impairment | 1/257 (0.4%) | 0/134 (0%) | ||
| Syncope | 1/257 (0.4%) | 0/134 (0%) | ||
| Loss of consciousness | 0/257 (0%) | 1/134 (0.7%) | ||
| Neuropathy peripheral | 0/257 (0%) | 1/134 (0.7%) | ||
| Thoracic outlet syndrome | 0/257 (0%) | 1/134 (0.7%) | ||
| Psychiatric disorders | ||||
| Aggression | 1/257 (0.4%) | 0/134 (0%) | ||
| Drug abuse | 0/257 (0%) | 1/134 (0.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary embolism | 0/257 (0%) | 1/134 (0.7%) | ||
Other (Not Including Serious) Adverse Events |
||||
| TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 243/257 (94.6%) | 131/134 (97.8%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 49/257 (19.1%) | 29/134 (21.6%) | ||
| Anaemia | 46/257 (17.9%) | 33/134 (24.6%) | ||
| Thrombocytopenia | 13/257 (5.1%) | 9/134 (6.7%) | ||
| Leukopenia | 10/257 (3.9%) | 7/134 (5.2%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 63/257 (24.5%) | 24/134 (17.9%) | ||
| Diarrhoea | 34/257 (13.2%) | 12/134 (9%) | ||
| Vomiting | 17/257 (6.6%) | 7/134 (5.2%) | ||
| Dry mouth | 13/257 (5.1%) | 6/134 (4.5%) | ||
| Abdominal pain | 12/257 (4.7%) | 7/134 (5.2%) | ||
| Abdominal pain upper | 11/257 (4.3%) | 12/134 (9%) | ||
| Constipation | 8/257 (3.1%) | 7/134 (5.2%) | ||
| General disorders | ||||
| Fatigue | 95/257 (37%) | 56/134 (41.8%) | ||
| Pyrexia | 80/257 (31.1%) | 53/134 (39.6%) | ||
| Influenza like illness | 66/257 (25.7%) | 35/134 (26.1%) | ||
| Asthenia | 59/257 (23%) | 38/134 (28.4%) | ||
| Chills | 21/257 (8.2%) | 12/134 (9%) | ||
| Injection site erythema | 15/257 (5.8%) | 9/134 (6.7%) | ||
| Infections and infestations | ||||
| Influenza | 5/257 (1.9%) | 8/134 (6%) | ||
| Sinusitis | 5/257 (1.9%) | 7/134 (5.2%) | ||
| Investigations | ||||
| Weight decreased | 14/257 (5.4%) | 6/134 (4.5%) | ||
| Neutrophil count decreased | 8/257 (3.1%) | 7/134 (5.2%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 46/257 (17.9%) | 21/134 (15.7%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 58/257 (22.6%) | 28/134 (20.9%) | ||
| Arthralgia | 32/257 (12.5%) | 14/134 (10.4%) | ||
| Back pain | 25/257 (9.7%) | 13/134 (9.7%) | ||
| Muscle spasms | 8/257 (3.1%) | 7/134 (5.2%) | ||
| Nervous system disorders | ||||
| Headache | 101/257 (39.3%) | 49/134 (36.6%) | ||
| Dizziness | 21/257 (8.2%) | 9/134 (6.7%) | ||
| Disturbance in attention | 13/257 (5.1%) | 8/134 (6%) | ||
| Dysgeusia | 6/257 (2.3%) | 7/134 (5.2%) | ||
| Psychiatric disorders | ||||
| Insomnia | 51/257 (19.8%) | 21/134 (15.7%) | ||
| Depression | 29/257 (11.3%) | 19/134 (14.2%) | ||
| Mood altered | 22/257 (8.6%) | 15/134 (11.2%) | ||
| Anxiety | 17/257 (6.6%) | 6/134 (4.5%) | ||
| Sleep disorder | 13/257 (5.1%) | 5/134 (3.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 32/257 (12.5%) | 22/134 (16.4%) | ||
| Dyspnoea | 23/257 (8.9%) | 11/134 (8.2%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 65/257 (25.3%) | 34/134 (25.4%) | ||
| Rash | 46/257 (17.9%) | 15/134 (11.2%) | ||
| Alopecia | 43/257 (16.7%) | 27/134 (20.1%) | ||
| Dry skin | 28/257 (10.9%) | 18/134 (13.4%) | ||
| Eczema | 4/257 (1.6%) | 9/134 (6.7%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Global Clinical Development Manager |
|---|---|
| Organization | Jan-Cil France |
| Phone | |
| ClinicalTrialDisclosure@its.jnj.com |
Responsible Party:
Janssen R&D Ireland
ClinicalTrials.gov Identifier:
NCT01290679
Other Study ID Numbers:
- CR017380
- TMC435-TiDP16-C216
- 2010-021174-11
First Posted:
Feb 7, 2011
Last Update Posted:
Jun 13, 2014
Last Verified:
Jun 1, 2014