Trial Outcomes & Findings for A Phase III Study of TMC435 in Genotype 1, Hepatitis C-infected Participants Who Failed to Respond to Previous IFN-based Therapy (NCT NCT01288209)
NCT ID: NCT01288209
Last Updated: 2014-01-24
Results Overview
The table below shows the observed percentage of participants in each treatment group with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at the EOT (Week 24 or 48) and at 12 weeks after the last dose of treatment (Week 36 or 60).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
106 participants
Primary outcome timeframe
EOT (Week 24 or 48) and Week 36 or 60
Results posted on
2014-01-24
Participant Flow
The study was conducted between 05-Jan-2011 to 05-Sep-2012 and recruited participants with chronic Hepatitis C Virus (HCV) infection from 23 study centers in Japan. A total of 108 participants were randomized, 106 started treatment, and 101 completed the study.
Participants with genotype 1 HCV-infection who failed a previous course of interferon (IFN) based therapy received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) until Week 12 (OR Week 24), followed by PR until Week 24/48 based on response-guided treatment (RGT).
Participant milestones
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR 24/48
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
Overall Study
STARTED
|
53
|
53
|
|
Overall Study
COMPLETED
|
51
|
50
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
Reasons for withdrawal
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR 24/48
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
3
|
|
Overall Study
Other
|
1
|
0
|
Baseline Characteristics
A Phase III Study of TMC435 in Genotype 1, Hepatitis C-infected Participants Who Failed to Respond to Previous IFN-based Therapy
Baseline characteristics by cohort
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR 24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
Total
n=106 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60 years
n=5 Participants
|
60 years
n=7 Participants
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: EOT (Week 24 or 48) and Week 36 or 60Population: The Full Analysis Set (FAS) consisted of all participants who received at least one dose of study drug during the study except for those who did not meet the major eligibility criteria for the study and participants who did not have efficacy data available after treatment with study medication.
The table below shows the observed percentage of participants in each treatment group with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at the EOT (Week 24 or 48) and at 12 weeks after the last dose of treatment (Week 36 or 60).
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 12 Weeks After the Last Dose of Treatment (SVR12)
|
52.8 Percentage of participants
|
35.8 Percentage of participants
|
SECONDARY outcome
Timeframe: EOT (Week 24 or 48) and Week 48 or 72Population: The Full Analysis Set (FAS) consisted of all participants who received at least one dose of study drug during the study except for those who did not meet the major eligibility criteria for the study and participants who did not have efficacy data available after treatment with study medication.
The table below shows the observed percentage of participants in each treatment group with a SVR24 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at the EOT (Week 24 or 48) and at 24 weeks after the last dose of treatment (Week 48 or 72).
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24)
|
50.9 Percentage of participants
|
35.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 3, Day 7, and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT, and Follow-up (FU) Weeks 4, 12, and 24Population: The Full Analysis Set (FAS) consisted of all participants who received at least one dose of study drug during the study except for those who did not meet the major eligibility criteria for the study and participants who did not have efficacy data available after treatment with study medication.
The table below shows the percentage of participants in each treatment group with a greater than (\>) or equal to (=) 2 log10 IU/mL drop from baseline in HCV RNA at each time point during treatment and post-treatment follow-up.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Day 3
|
96.2 Percentage of participants
|
96.2 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Day 7
|
100 Percentage of participants
|
100 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 2
|
100 Percentage of participants
|
96.2 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 3
|
100 Percentage of participants
|
94.3 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 4
|
100 Percentage of participants
|
90.6 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 8
|
88.7 Percentage of participants
|
90.6 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 12
|
88.7 Percentage of participants
|
86.8 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 16
|
84.9 Percentage of participants
|
83.0 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 20
|
84.9 Percentage of participants
|
79.2 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 24
|
84.9 Percentage of participants
|
75.5 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 28
|
75.5 Percentage of participants
|
69.8 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
week 36
|
52.8 Percentage of participants
|
41.5 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 48
|
50.9 Percentage of participants
|
37.7 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 60
|
50.9 Percentage of participants
|
35.8 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
Week 72
|
50.9 Percentage of participants
|
35.8 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
EOT
|
88.7 Percentage of participants
|
90.6 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
FU Week 4
|
77.4 Percentage of participants
|
81.1 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
FU Week 12
|
52.8 Percentage of participants
|
39.6 Percentage of participants
|
|
The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up
FU Week 24
|
50.9 Percentage of participants
|
35.8 Percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOTPopulation: The Full Analysis Set (FAS) consisted of all participants who received at least one dose of study drug during the study except for those who did not meet the major eligibility criteria for the study and participants who did not have efficacy data available after treatment with study medication.
The table below shows the percentage of participants with undetectable HCV RNA (\<1.2 log10 IU/mL) during treatment at Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT (Week 24 or 48).
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 24
|
79.2 Percentage of participants
|
71.7 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 4
|
58.5 Percentage of participants
|
50.9 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 12
|
84.9 Percentage of participants
|
79.2 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 36
|
52.8 Percentage of participants
|
35.8 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 48
|
50.9 Percentage of participants
|
35.8 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 60
|
50.9 Percentage of participants
|
35.8 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 72
|
50.9 Percentage of participants
|
35.8 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
EOT
|
83.0 Percentage of participants
|
84.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 24, 48, EOT (Weeks 24 or 48), SVR12 (Weeks 36 or 60), and SVR24 (Weeks 48 or 72)Population: The Full Analysis Set (FAS) consisted of all participants who received at least one dose of study drug during the study except for those who did not meet the major eligibility criteria for the study and participants who did not have efficacy data available after treatment with study medication.
The table below shows the percentage of participants with undetectable HCV RNA at Weeks 24, 48, end of treatment (EOT), at the time of assessment for a sustained virologic response (SVR) 12 weeks after the last planned dose (SVR12) (Week 36 or 60), and SVR24 (Week 48 or 72) who did not achieve undetectable HCV RNA levels at Week 12. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x) if different from the "Number of Participants Analyzed." Results are not available for Weeks 24, 48, and EOT because there were no participants who met the criteria for a SVR at those time points.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12
SVR12 (Weeks 36 or 60) (n=6; n=8)
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12
SVR24 (Weeks 48 or 72) (n=6; n=8)
|
0.0 Percentage of participants
|
0.0 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12
Week 24
|
NA Percentage of participants
Data analysis was not performed at Week 24 because no participants met criteria for SVR.
|
NA Percentage of participants
Data analysis was not performed at Week 24 because no participants met criteria for SVR.
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12
Week 48
|
NA Percentage of participants
Data analysis was not performed at Week 48 because no participants met criteria for SVR.
|
NA Percentage of participants
Data analysis was not performed at Week 48 because no participants met criteria for SVR.
|
|
The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels During Treatment for Participants Who Did Not Achieve Undetectable Plasma HCV RNA Levels at Week 12
EOT
|
NA Percentage of participants
Data analysis was not performed at EOT because no participants met criteria for SVR.
|
NA Percentage of participants
Data analysis was not performed at EOT because no participants met criteria for SVR.
|
SECONDARY outcome
Timeframe: Up to EOT (Week 24 or 48)Population: The Full Analysis Set (FAS) consisted of all participants who received at least one dose of study drug during the study except for those who did not meet the major eligibility criteria for the study and participants who did not have efficacy data available after treatment with study medication.
The table below shows the number of all participants in each treatment group who experienced viral breakthrough during the treatment period in the study (Baseline to end of treatment \[EOT\], ie, Week 24 or 48). Viral breakthrough is 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 or a confirmed value of plasma HCV RNA of \> 2.0 log10 IU/mL in all participants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
The Number of Participants With Viral Breakthrough During the Study
|
7 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Up to 72 weeksPopulation: The Full Analysis Set (FAS) consisted of all participants who received at least one dose of study drug during the study except for those who did not meet the major eligibility criteria for the study and participants who did not have efficacy data available after treatment with study medication.
The table below shows the number of participants in each treatment group who demonstrated viral relapse during the study. Viral relapse is defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at EOT and detectable HCV RNA during follow-up or detectable HCV RNA at the time points for a sustained viral response (SVR) assessment. The incidence of viral relapse was only calculated for participants with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=44 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=45 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
The Number of Participants Demonstrating Viral Relapse During the Study
|
17 Participants
|
23 Participants
|
SECONDARY outcome
Timeframe: EOT (Week 24 or 48)Population: The Full Analysis Set (FAS) consisted of all participants who received at least one dose of study drug during the study except for those who did not meet the major eligibility criteria for the study and participants who did not have efficacy data available after treatment with study medication.
The table below shows the number of participants in each treatment group with abnormal ALT levels at baseline (Day 1) who achieved normalization of ALT levels defined as having an ALT value less than or equal to the Upper Limit of Normality (ie, 40 IU/mL) at the EOT. At Baseline, 34/53 participants in the TMC435 100 mg 12 Wks PR 24/48 treatment group and 35/53 participants in the TMC435 100 mg 24 Wks PR 24/48 treatment group had abnormal ALT levels.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=34 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=35 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
The Number Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)
|
20 Participants
|
28 Participants
|
SECONDARY outcome
Timeframe: Week 24Population: The Full Analysis Set (FAS) consisted of all randomized participants who received at least one dose of study drug during the study except for those who did not meet the major eligibility criteria for the study and participants who did not have efficacy data available after treatment with study medication.
The table below shows the percentage of participants in each treatment group who met RGT criteria (ie, who had plasma levels of hepatitis C virus ribonucleic acid \[HCV RNA\] \<1.2 log10 IU/mL detectable/undetectable at Week 4 and \<1.2 log 10 IU/mL undetectable at Week 12) and completed treatment with PegIFNα-2a and RBV at Week 24. Participants in the TMC435 treatment groups not meeting RGT criteria continued treatment with PegIFNα-2a and RBV to Week 48.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFNα-2a) and Ribavirin (RBV) at Week 24
|
81.1 Percentage of participants
|
73.6 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 12, Week 24, and Overall (Weeks 4, 12, and 24)Population: Pharmacokinetic analysis was performed in the pharmacokinetic (PK) population, defined as all participants from whom sparse blood samples were drawn and who received at least 1 dose of study medication.
The table below shows median (range) TMC435 predose plasma concentration (C0h) values and TMC435 maximum plasma concentration (Cmax) values for participants in each treatment group at Week 12, Week 24, and Overall (Weeks 4, 12, and 24). The time frame of "Overall" representes the median exposure estimate using all available data collected at Weeks 4, 12, and 24 for each participant in the study. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x) if different from the "Number of Participants Analyzed."
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
Plasma Concentrations of TMC435
C0h (Week 12) (n=47; n=44)
|
1844 ng/mL
Interval 190.0 to 10444.0
|
910 ng/mL
Interval 149.0 to 10562.0
|
|
Plasma Concentrations of TMC435
C0h (Week 24) (n=0; n=40)
|
NA ng/mL
Participants in this treatment group received TMC435 for 12 weeks; therefore, data at Week 24 is not available.
|
866 ng/mL
Interval 147.0 to 11531.0
|
|
Plasma Concentrations of TMC435
C0h (Overall) (n=53; n=53)
|
1784 ng/mL
Interval 194.0 to 8461.0
|
906 ng/mL
Interval 142.0 to 10209.0
|
|
Plasma Concentrations of TMC435
Cmax (Week 12) (n=47; n=44)
|
3408 ng/mL
Interval 1618.0 to 12074.0
|
2476 ng/mL
Interval 1547.0 to 12207.0
|
|
Plasma Concentrations of TMC435
Cmax (Week 24) (n=0; n=40)
|
NA ng/mL
Participants in this treatment group received TMC435 for 12 weeks; therefore, data at Week 24 is not available.
|
2443 ng/mL
Interval 1541.0 to 13191.0
|
|
Plasma Concentrations of TMC435
Cmax (Overall) (n=53; n=53)
|
3401 ng/mL
Interval 1631.0 to 10074.0
|
2488 ng/mL
Interval 1536.0 to 11882.0
|
SECONDARY outcome
Timeframe: Week 12, Week 24, and Overall (Weeks 4, 12, and 24)Population: Pharmacokinetic analysis was performed in the pharmacokinetic (PK) population, defined as all participants from whom sparse blood samples were drawn and who received at least 1 dose of study medication.
The table below shows the median (range) AUC24h values for participants in each treatment group at Week 12, Week 24, and Overall (Weeks 4, 12, and 24). The time frame of "Overall" represents the median exposure estimate using all available data collected at Weeks 4, 12, and 24 for each participant in the study. The number of participants analyzed is listed at each time point in order of the treatment groups from left to right in the table (ie, Week x, n=x, x) if different from the "Number of Participants Analyzed."
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR24/48
n=53 Participants
Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable plasma HCV RNA levels at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
AUC24h (Week 12) (n=47; n=44)
|
62993 ng.h/mL
Interval 18375.0 to 271080.0
|
39867 ng.h/mL
Interval 16608.0 to 274140.0
|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
AUC24h (Week 24) (n=0; n=40)
|
NA ng.h/mL
Participants in this treatment group received TMC435 for 12 weeks; therefore, data at Week 24 is not available.
|
38931 ng.h/mL
Interval 16507.0 to 297640.0
|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
Overall (n=53; n=53)
|
62313 ng.h/mL
Interval 18612.0 to 223155.0
|
40014 ng.h/mL
Interval 16296.0 to 266070.0
|
Adverse Events
TMC435 100 mg 12 Wks + PR 24/48
Serious events: 2 serious events
Other events: 53 other events
Deaths: 0 deaths
TMC435 100 mg 24 Wks + PR 24/48
Serious events: 3 serious events
Other events: 52 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=53 participants at risk
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR 24/48
n=53 participants at risk
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Laceration
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
Other adverse events
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=53 participants at risk
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
TMC435 100 mg 24 Wks + PR 24/48
n=53 participants at risk
Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin ( PR) for 24 weeks (Wks). Treatment was stopped at Week 24 if participants achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable at Week 4, and undetectable HCV RNA at Week 12. All other participants continued PR until Week 48.
|
|---|---|---|
|
General disorders
Pyrexia
|
62.3%
33/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
58.5%
31/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
General disorders
Malaise
|
56.6%
30/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
45.3%
24/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
General disorders
Fatigue
|
17.0%
9/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
20.8%
11/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
General disorders
Injection site reaction
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
22.6%
12/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
General disorders
Injection site erythema
|
9.4%
5/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
White blood cell count decreased
|
62.3%
33/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
58.5%
31/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Neutrophil count decreased
|
52.8%
28/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
52.8%
28/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Platelet count decreased
|
50.9%
27/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
39.6%
21/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Haemoglobin decreased
|
24.5%
13/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
22.6%
12/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Blood bilirubin increased
|
17.0%
9/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
20.8%
11/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Haematocrit decreased
|
15.1%
8/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
15.1%
8/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Red blood cell count decreased
|
15.1%
8/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
9.4%
5/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Blood cholesterol decreased
|
13.2%
7/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
9.4%
5/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Blood triglycerides increased
|
13.2%
7/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
13.2%
7/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
High density lipoprotein decreased
|
13.2%
7/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Alanine aminotransferase increased
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Aspartate aminotransferase increased
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Blood calcium decreased
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Blood thyroid stimulating hormone increased
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Bilirubin conjugated increased
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Blood alkaline phosphatase increased
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Lipase increased
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Low density lipoprotein decreased
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Investigations
Weight decreased
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
9.4%
5/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
39.6%
21/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
28.3%
15/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Skin and subcutaneous tissue disorders
Rash
|
37.7%
20/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
43.4%
23/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
30.2%
16/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
22.6%
12/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Skin and subcutaneous tissue disorders
Erythema
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Blood and lymphatic system disorders
Anaemia
|
52.8%
28/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
56.6%
30/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Blood and lymphatic system disorders
Leukopenia
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
15.1%
8/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Gastrointestinal disorders
Stomatitis
|
20.8%
11/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
18.9%
10/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Gastrointestinal disorders
Diarrhoea
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
13.2%
7/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Gastrointestinal disorders
Nausea
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
17.0%
9/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Gastrointestinal disorders
Abdominal discomfort
|
9.4%
5/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
17.0%
9/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Gastrointestinal disorders
Constipation
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Gastrointestinal disorders
Dental caries
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Gastrointestinal disorders
Vomiting
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Gastrointestinal disorders
Cheilitis
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Nervous system disorders
Headache
|
43.4%
23/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
43.4%
23/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Nervous system disorders
Dysgeusia
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Nervous system disorders
Dizziness
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
24.5%
13/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
24.5%
13/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
13.2%
7/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
11.3%
6/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Metabolism and nutrition disorders
Decreased appetite
|
22.6%
12/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
28.3%
15/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.8%
11/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Infections and infestations
Nasopharyngitis
|
18.9%
10/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
30.2%
16/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Infections and infestations
Cystitis
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
7.5%
4/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Psychiatric disorders
Insomnia
|
9.4%
5/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
18.9%
10/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Eye disorders
Retinopathy
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Eye disorders
Dry eye
|
1.9%
1/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Injury, poisoning and procedural complications
Contusion
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
3.8%
2/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
5.7%
3/53 • Up to approximately 52 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days).
|
Additional Information
Manager
Janssen Pharmaceutical K.K., Japan
Phone: 81 3 44115639
Results disclosure agreements
- Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
- Publication restrictions are in place
Restriction type: OTHER