Trial Outcomes & Findings for A Phase III Study of TMC435 in Treatment-naive, Genotype 1, Hepatitis C-infected Patients (NCT NCT01292239)
NCT ID: NCT01292239
Last Updated: 2014-01-17
Results Overview
The table below shows the observed percentage of participants with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at 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
183 participants
Primary outcome timeframe
EOT (up to Week 24 or 48) and 12 weeks after the EOT (up to Week 36 or 60)
Results posted on
2014-01-17
Participant Flow
The study was conducted between 17-January-2011 and 22-October-2012 and recruited participants with chronic genotype 1 Hepatitis C Virus (HCV) infection who were treatment-naïve from 37 study centers in Japan. A total 183 participants were randomized and started treatment; 172 completed the study.
Treatment-naïve HCV-infected participants were assigned to 1 of 2 groups to receive TMC435 100 mg once daily with PegIFN alpha-2a and ribavirin (PR) until Week 12, followed by PR until Week 24 or 48 OR placebo with PR until Week 12, followed by PR until Week 48.
Participant milestones
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Overall Study
STARTED
|
123
|
60
|
|
Overall Study
COMPLETED
|
119
|
53
|
|
Overall Study
NOT COMPLETED
|
4
|
7
|
Reasons for withdrawal
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Overall Study
Other
|
1
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
6
|
Baseline Characteristics
A Phase III Study of TMC435 in Treatment-naive, Genotype 1, Hepatitis C-infected Patients
Baseline characteristics by cohort
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=123 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=60 Participants
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
Total
n=183 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56 years
n=5 Participants
|
54.5 years
n=7 Participants
|
55 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
84 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
120 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: EOT (up to Week 24 or 48) and 12 weeks after the EOT (up to Week 36 or 60)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 observed percentage of participants with a SVR12 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at 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 + PR 24/48
n=123 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=60 Participants
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 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)
|
88.6 Percentage of participants
Interval 83.63 to 94.39
|
61.7 Percentage of participants
Interval 49.6 to 73.47
|
SECONDARY outcome
Timeframe: EOT (up to Week 24 or 48) and 24 weeks after the after the last dose of treatment (up to Week 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 observed percentage of participants with a SVR24 defined as undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (EOT, defined as up to Week 24 or 48) and at 24 weeks after the last dose of treatment (up to Week 48 or 72).
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=123 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=60 Participants
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants With a Sustained Virologic Response at the End of Treatment (EOT) and 24 Weeks After the Last Dose of Treatment (SVR24)
|
88.6 Percentage of participants
|
56.7 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 3, Day 7 and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 42, 48, 52, 60, 72, EOT (up to Week 24 or 48), FU Week 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 with greater than (\>) or equal to (=) 2 log10 IU/mL drop from baseline in plasma levels of HCV RNA at each time point during treatment and post-treatment follow-up (FU).
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=123 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=60 Participants
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 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
|
98.4 Percentage of participants
|
26.7 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
Day 7
|
99.2 Percentage of participants
|
46.7 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 2
|
100.0 Percentage of participants
|
58.3 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 3
|
100.0 Percentage of participants
|
71.7 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 4
|
99.2 Percentage of participants
|
76.7 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 8
|
100.0 Percentage of participants
|
88.3 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 12
|
97.6 Percentage of participants
|
88.3 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 16
|
95.1 Percentage of participants
|
88.3 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 20
|
95.9 Percentage of participants
|
86.7 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 24
|
92.7 Percentage of participants
|
83.3 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 28
|
94.3 Percentage of participants
|
80.0 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 36
|
87.8 Percentage of participants
|
80.0 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 42
|
2.4 Percentage of participants
|
76.7 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 48
|
86.2 Percentage of participants
|
75.0 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 52
|
0.0 Percentage of participants
|
71.7 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
|
88.6 Percentage of participants
|
65.0 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 72
|
88.6 Percentage of participants
|
58.3 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
EOT (up to Week 24 or 48)
|
99.2 Percentage of participants
|
96.7 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
FU Week 4
|
96.7 Percentage of participants
|
83.3 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
FU Week 12
|
89.4 Percentage of participants
|
65.0 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
FU Week 24
|
88.6 Percentage of participants
|
58.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT (up to 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 percentage of participants with undetectable plasma levels of HCV RNA \<1.2 log10 IU/mL during treatment at Weeks 4, 12, 24, 36, 48, 60, 72, and at the EOT (up to Week 24 or 48).
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=123 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=60 Participants
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 12
|
96.7 Percentage of participants
|
63.3 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 4
|
83.7 Percentage of participants
|
13.3 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 24
|
91.9 Percentage of participants
|
73.3 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 36
|
87.0 Percentage of participants
|
71.7 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 48
|
86.2 Percentage of participants
|
75.0 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 60
|
88.6 Percentage of participants
|
61.7 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
Week 72
|
88.6 Percentage of participants
|
56.7 Percentage of participants
|
|
The Percentage of Participants With Undetectable Plasma Levels of Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT)
EOT (up to Week 24 or 48)
|
99.2 Percentage of participants
|
88.3 Percentage of participants
|
SECONDARY outcome
Timeframe: Up to EOT (up to 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.
Viral breakthrough was defined as a confirmed increase of \> 1 log10 IU/mL in plasma levels of hepatitis C virus (HCV) ribonucleic acid (RNA)l from the lowest level reached or a confirmed value of plasma HCV RNA of \> 2.0 log10 IU/mL in participants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable during the treatment period (up to the end of treatment \[EOT\]).
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=123 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=60 Participants
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Number of Participants With Viral Breakthrough
|
1 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: Up to Week 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 number of participants who demonstrated viral relapse, defined as undetectable plasma levels of hepatitis C virus (HCV) ribonucleic acid (RNA) at the End of Treatment (EOT) (up to Week 24 or 48) and detectable HCV RNA during follow-up or detectable plasma levels of HCV RNA at the time points of sustained virologic response (SVR) assessment. The incidence of viral relapse was only calculated for participants with undetectable plasma levels of HCV RNA at the EOT and with at least one follow-up HCV RNA. measurement.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=118 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=49 Participants
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Number of Participants Demonstrating Viral Relapse
|
9 Participants
|
15 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 1) to EOT (up to 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 with abnormal ALT levels at Baseline (Day 1) who achieved normal ALT levels at the EOT (up to Week 24 or 48). At Baseline, 61/123 participants in the TMC435 treatment group and 25/60 participants in the Placebo treatment group had abnormal ALT levels. At the EOT, 47 (77.0%) participants in the TMC435 treatment group and 18 (72.0%) participants in the Placebo treatment group had ALT levels that returned to normal (or normalization of ALT levels defined as an ALT value less than or equal to the Upper Limit of Normality \[ie, 40 IU/mL\] at EOT.).
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=61 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=25 Participants
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT)
|
47 Participants
|
18 Participants
|
SECONDARY outcome
Timeframe: Week 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 the TMC435 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 pegIFN alpha 2a and RBV at Week 24. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group continued treatment with PegIFN alpha 2a and RBV to Week 48.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=123 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
The Percentage of Participants in the TMC435 Treatment Group Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2a (PegIFN Alpha-2a) and Ribavirin (RBV) at Week 24
|
91.9 Percentage of participants
|
—
|
SECONDARY outcome
Timeframe: Overall (ie, Up to Week 12)Population: Pharmacokinetic (PK) analysis was performed in the 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) predose plasma concentration (C0h) values and median (range) maximum plasma concentration (Cmax) values for TMC435 for all participants in the TMC435 treatment group. The time frame of "Overall" (up to Week 12) represents the median exposure estimate using all available data for each participant in the study.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=123 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Plasma Concentrations of TMC435
C0h
|
1005 ng/mL
Interval 64.0 to 8543.0
|
—
|
|
Plasma Concentrations of TMC435
Cmax
|
2601 ng/mL
Interval 1317.0 to 10161.0
|
—
|
SECONDARY outcome
Timeframe: Overall (Up to Week 12)Population: Pharmacokinetic (PK) analysis was performed in the 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 TMC435 for all participants in the TMC435 treatment group who received TMC435 for up to 12 weeks. The time frame of "Overall" (up to Week 12) represents the median exposure estimate using all available data for each participant in the study.
Outcome measures
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=123 Participants
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
|
42721 ng.h/mL
Interval 11569.0 to 225205.0
|
—
|
Adverse Events
TMC435 100 mg 12 Wks + PR 24/48
Serious events: 4 serious events
Other events: 123 other events
Deaths: 0 deaths
PBO 12 Wks + PR 48
Serious events: 6 serious events
Other events: 60 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TMC435 100 mg 12 Wks + PR 24/48
n=123 participants at risk
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=60 participants at risk
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Erythema
|
1.6%
2/123 • 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%
0/60 • 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).
|
|
Cardiac disorders
Cardiac failure
|
0.81%
1/123 • 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%
0/60 • 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
Peritonitis
|
0.81%
1/123 • 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%
0/60 • 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
Glomerulonephritis membranous
|
0.81%
1/123 • 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%
0/60 • 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).
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.00%
0/123 • 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).
|
1.7%
1/60 • 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
|
0.00%
0/123 • 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).
|
1.7%
1/60 • 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
Hepatic mass
|
0.00%
0/123 • 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).
|
1.7%
1/60 • 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
Inclusion body myositis
|
0.00%
0/123 • 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).
|
1.7%
1/60 • 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
Intervertebral disc protrusion
|
0.00%
0/123 • 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).
|
1.7%
1/60 • 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
|
0.00%
0/123 • 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).
|
1.7%
1/60 • 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
|
0.00%
0/123 • 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).
|
1.7%
1/60 • 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=123 participants at risk
Participants were given TMC435 100 mg once daily plus peginterferon alpha-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved plasma levels of Hepatitis C virus ribonucleic acid (HCV RNA) \< 1.2 log10 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48).
|
PBO 12 Wks + PR 48
n=60 participants at risk
Participants were given placebo (PBO) once daily plus peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFNα-2a (P) and RBV (R) until Week 48 (PR 48).
|
|---|---|---|
|
Metabolism and nutrition disorders
Decreased appetite
|
22.8%
28/123 • 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).
|
33.3%
20/60 • 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
|
17.1%
21/123 • 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%
17/60 • 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
|
22.0%
27/123 • 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).
|
41.7%
25/60 • 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
Depression
|
0.00%
0/123 • 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).
|
5.0%
3/60 • 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
|
63.4%
78/123 • 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).
|
68.3%
41/60 • 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
|
56.1%
69/123 • 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).
|
61.7%
37/60 • 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
|
48.8%
60/123 • 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).
|
38.3%
23/60 • 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
|
22.0%
27/123 • 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).
|
15.0%
9/60 • 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
|
16.3%
20/123 • 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).
|
6.7%
4/60 • 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
|
13.8%
17/123 • 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).
|
8.3%
5/60 • 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
|
13.0%
16/123 • 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).
|
13.3%
8/60 • 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
|
10.6%
13/123 • 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).
|
10.0%
6/60 • 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
|
7.3%
9/123 • 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).
|
1.7%
1/60 • 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
|
7.3%
9/123 • 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).
|
13.3%
8/60 • 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
Pyrexia
|
61.0%
75/123 • 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).
|
51.7%
31/60 • 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
|
42.3%
52/123 • 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).
|
45.0%
27/60 • 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
|
17.9%
22/123 • 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).
|
15.0%
9/60 • 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
|
10.6%
13/123 • 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).
|
11.7%
7/60 • 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
|
3.3%
4/123 • 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).
|
10.0%
6/60 • 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
Administration site reaction
|
2.4%
3/123 • 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).
|
5.0%
3/60 • 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
|
46.3%
57/123 • 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).
|
61.7%
37/60 • 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
|
35.8%
44/123 • 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).
|
46.7%
28/60 • 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
|
28.5%
35/123 • 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).
|
30.0%
18/60 • 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
|
13.8%
17/123 • 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).
|
6.7%
4/60 • 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
Eczema
|
8.1%
10/123 • 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).
|
6.7%
4/60 • 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
|
6.5%
8/123 • 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).
|
15.0%
9/60 • 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
Seborrhoeic dermatitis
|
1.6%
2/123 • 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).
|
8.3%
5/60 • 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
|
56.9%
70/123 • 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).
|
60.0%
36/60 • 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
|
6.5%
8/123 • 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).
|
1.7%
1/60 • 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
|
5.7%
7/123 • 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).
|
5.0%
3/60 • 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
|
4.1%
5/123 • 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).
|
5.0%
3/60 • 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
|
22.8%
28/123 • 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).
|
20.0%
12/60 • 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
|
16.3%
20/123 • 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%
17/60 • 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
|
13.0%
16/123 • 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).
|
8.3%
5/60 • 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
|
13.0%
16/123 • 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).
|
20.0%
12/60 • 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
|
7.3%
9/123 • 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).
|
8.3%
5/60 • 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
|
4.9%
6/123 • 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).
|
8.3%
5/60 • 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 pain upper
|
4.1%
5/123 • 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).
|
10.0%
6/60 • 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
|
3.3%
4/123 • 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).
|
5.0%
3/60 • 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 pain
|
1.6%
2/123 • 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).
|
8.3%
5/60 • 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
Gingivitis
|
1.6%
2/123 • 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).
|
5.0%
3/60 • 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
Toothache
|
0.81%
1/123 • 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).
|
5.0%
3/60 • 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
|
43.9%
54/123 • 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).
|
43.3%
26/60 • 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
|
16.3%
20/123 • 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).
|
13.3%
8/60 • 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
|
3.3%
4/123 • 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).
|
6.7%
4/60 • 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
|
24.4%
30/123 • 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).
|
23.3%
14/60 • 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
|
7.3%
9/123 • 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).
|
15.0%
9/60 • 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
|
7.3%
9/123 • 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).
|
18.3%
11/60 • 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
Arthritis
|
0.00%
0/123 • 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).
|
5.0%
3/60 • 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
Gastroenteritis
|
0.81%
1/123 • 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).
|
5.0%
3/60 • 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
Retinal exudates
|
5.7%
7/123 • 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).
|
3.3%
2/60 • 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
Retinal haemorrhage
|
5.7%
7/123 • 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).
|
1.7%
1/60 • 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
|
5.7%
7/123 • 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).
|
8.3%
5/60 • 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
|
0.81%
1/123 • 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).
|
5.0%
3/60 • 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
|
8.9%
11/123 • 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).
|
13.3%
8/60 • 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
|
4.9%
6/123 • 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).
|
8.3%
5/60 • 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).
|
|
Ear and labyrinth disorders
Vertigo
|
6.5%
8/123 • 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%
0/60 • 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
|
6.5%
8/123 • 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).
|
3.3%
2/60 • 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
Director
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