Trial Outcomes & Findings for A Study of TMC435 in Genotype 1, Hepatitis C-infected Patients Who Relapsed After Previous Interferon (IFN)-Based Therapy (NCT NCT01290731)

Last Updated: 2014-02-04

Results Overview

The table below shows the percentage of participants with an SVR12 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) 12 weeks after the last dose of treatment (Week 36 or 60).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

49 participants

Primary outcome timeframe

Week 36 or 60

Results posted on

2014-02-04

Participant Flow

The study was conducted between 22-Dec-2010 to 13-Aug-2012 and recruited participants with chronic Hepatitis C Virus (HCV) infection from 12 study centers in Japan. A total of 49 participants with chronic genotype 1 HCV infection were randomized and started treatment. A total of 48 participants completed the study.

HCV-infected participants who received at least 24 weeks of interferon (IFN)-based therapy and relapsed within 1 year after the last medication intake received treatment with TMC435 100 mg once daily with PegIFN alpha-2a and ribavirin (PR) until Week 12,followed by PR until Week 24/48 based on response-guided treatment (RGT) guidelines.

Participant milestones

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 (PR 24). Treatment was to be stopped at Week 24 in participants who 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 (PR 48).
Overall Study STARTED	49
Overall Study COMPLETED	48
Overall Study NOT COMPLETED	1

Reasons for withdrawal

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 (PR 24). Treatment was to be stopped at Week 24 in participants who 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 (PR 48).
Overall Study Withdrawal by Subject	1

Baseline Characteristics

A Study of TMC435 in Genotype 1, Hepatitis C-infected Patients Who Relapsed After Previous Interferon (IFN)-Based Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TMC435 100 mg 12 Wks + PR 24/48 n=49 Participants Participants received TMC435 100 mg once daily with PegIFNa-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who 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 (PR 48).
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	TMC435 100 mg 12 Wks + PR24/48 n=49 Participants Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants continued PR until Week 48 (PR 48).
The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12)	95.9 Percentage of participants

SECONDARY outcome

Timeframe: Week 48 or 60

The table below shows the percentage of participants with a SVR24 defined as participants with undetectable plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at the end of treatment (Week 24 or 48) and at 24 weeks after the last dose of treatment (Week 48 or 72).

Outcome measures

Outcome measures
Measure	TMC435 100 mg 12 Wks + PR24/48 n=49 Participants Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants continued PR until Week 48 (PR 48).
The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24)	89.8 Percentage of participants

SECONDARY outcome

Timeframe: Days 3 and 7, Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT, and follow-up (FU) Weeks 4, 12, and 24

The table below shows the percentage of participants with greater than or equal to 2 log10 IU/mL drop from baseline in plasma HCV RNA at each time point during treatment, at the end of treatment (Week 24 or 48), and post-treatment follow-up.

Outcome measures

Outcome measures
Measure	TMC435 100 mg 12 Wks + PR24/48 n=49 Participants Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants continued PR 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	93.9 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	100.0 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 2	100.0 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 3	98.0 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 4	100.0 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 8	100.0 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 12	100.0 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 16	98.0 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	100.0 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 24	95.9 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	100.0 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	93.9 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	89.8 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 60	89.8 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	89.8 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	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 FU Week 4	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 FU Week 12	95.9 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	91.8 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT

The table below shows the percentage of participants with undetectable HCV RNA (defined as less than 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

Outcome measures
Measure	TMC435 100 mg 12 Wks + PR24/48 n=49 Participants Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants continued PR until Week 48 (PR 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 4	81.6 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	100.0 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 24	95.9 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 36	91.8 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	89.8 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	89.8 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	89.8 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	100.0 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 until end of treatment (EOT [Week 24 or 48])

Viral breakthrough was defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels from the lowest level reached or a confirmed value of plasma HCV RNA of \> 2.0 log10 IU/mL in particpants whose plasma HCV RNA level had previously been below 1.2 log10 IU/mL detectable or undetectable during the treatment period. The table below shows that no viral breakthrough was noted in any participants during the treatment period of the study.

Outcome measures

Outcome measures
Measure	TMC435 100 mg 12 Wks + PR24/48 n=49 Participants Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants continued PR until Week 48 (PR 48).
The Number of Participants With Viral Breakthrough	0 Participants

SECONDARY outcome

Timeframe: Up to 72 weeks

The table below shows the number of participants who demonstrated viral relapse, defined as undetectable Hepatitis C Virus Ribonucleic Acid (HCV RNA) at end of treatment (EOT) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of sustained virologic response (SVR) assessment . The incidence of viral relapse was calculated for participants with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement.

Outcome measures

Outcome measures
Measure	TMC435 100 mg 12 Wks + PR24/48 n=49 Participants Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants continued PR until Week 48 (PR 48).
The Number of Participants Demonstrating Viral Relapse	4 Participants

SECONDARY outcome

Timeframe: Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and 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) TMC435 predose plasma concentration (C0h) values and the TMC435 maximum plasma concentration (Cmax) values for all participants who received TMC435 for up to 12 weeks. "Overall" is the median exposure estimate using all available data for each participant in the study.Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12).

Outcome measures

Outcome measures
Measure	TMC435 100 mg 12 Wks + PR24/48 n=49 Participants Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants continued PR until Week 48 (PR 48).
Plasma Concentrations of TMC435 C0h	1822 ng/mL Interval 145.0 to 10693.0
Plasma Concentrations of TMC435 Cmax	3440 ng/mL Interval 1545.0 to 12273.0

SECONDARY outcome

Timeframe: Overall (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12)

The table below shows the median (range) AUC24h values for TMC435 for all participants who received TMC435 for up to 12 weeks. "Overall" is the median exposure estimate using all available data for each participant in the study. Sparse blood samples were collected during the study (blood sampling times were 3 and 5 hours post- dose at Week 2 and Week 8 and pre-dose and 2 hours post-dose at Week 4 and Week 12).

Outcome measures

Outcome measures
Measure	TMC435 100 mg 12 Wks + PR24/48 n=49 Participants Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants continued PR until Week 48 (PR 48).
Area Under the Plasma Concentration-time Curve From 0 to 24 Hrs (AUC24h) for TMC435	63261 ng.h/mL Interval 16480.0 to 276230.0

SECONDARY outcome

Timeframe: EOT (Week 24 or 48)

The table below shows the number of participants with abnormal ALT levels at baseline (Day 1) who achieved 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). At baseline, 15/49 participants had abnormal ALT levels.

Outcome measures

Outcome measures
Measure	TMC435 100 mg 12 Wks + PR24/48 n=15 Participants Participants received TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment was to be stopped at Week 24 in participants who achieved plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels \<1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants continued PR 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)	11 Participants

Adverse Events

TMC435 100 mg 12 Wks + PR 24/48

Serious events: 6 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TMC435 100 mg 12 Wks + PR 24/48 n=49 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 (PR 24). Treatment was to be stopped at Week 24 in participants who 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 (PR 48).
Infections and infestations Appendicitis	2.0% 1/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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 Herpes zoster	2.0% 1/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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 Pneumonia	2.0% 1/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	2.0% 1/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	2.0% 1/49 • Up to approximately 28 weeks (includes all serious and other adverse events that newly occurred or worsened after treatment with TMC435, PegIFNα-2b or ribavirin, until the end date of the last study medication intake + 28 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	2.0% 1/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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 Cerebral haemorrhage	2.0% 1/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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

Other adverse events
Measure	TMC435 100 mg 12 Wks + PR 24/48 n=49 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 (PR 24). Treatment was to be stopped at Week 24 in participants who 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 (PR 48).
General disorders Pyrexia	73.5% 36/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	44.9% 22/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	22.4% 11/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	61.2% 30/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	61.2% 30/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	44.9% 22/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	40.8% 20/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	26.5% 13/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	22.4% 11/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	18.4% 9/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	14.3% 7/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	14.3% 7/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	12.2% 6/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	10.2% 5/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	10.2% 5/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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 albumin decreased	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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 lactate dehydrogenase increased	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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 Monocyte percentage increased	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	38.8% 19/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	34.7% 17/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	32.7% 16/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	16.3% 8/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	10.2% 5/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	20.4% 10/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	20.4% 10/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	18.4% 9/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	14.3% 7/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	51.0% 25/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	10.2% 5/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	40.8% 20/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	26.5% 13/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	16.3% 8/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	44.9% 22/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	20.4% 10/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	28.6% 14/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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 Hypoalbuminaemia	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	12.2% 6/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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 function abnormal	10.2% 5/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	8.2% 4/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	10.2% 5/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	6.1% 3/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	10.2% 5/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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	10.2% 5/49 • Up to approximately 28 weeks (includes all serious and other adverse events that 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