A Study of TMC435 in Genotype 1, Hepatitis C-infected Patients Who Relapsed After Previous Interferon (IFN)-Based Therapy
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin in genotype 1 hepatitis C virus (HCV)-infected participants who relapsed after previous interferon (IFN)-based therapy in Japan.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a single-arm study to evaluate the efficacy and safety of TMC435 in combination with the standard of care (SoC), PegIFNα-2a (P) and ribavirin (R), in adult, genotype 1 HCV-infected participants who relapsed after previous IFN-based therapy in Japan. The study objective is to evaluate the efficacy of TMC435 by the percentage of participants with undetectable HCV ribonucleic acid (RNA). Participants will receive 12 weeks of treatment with TMC435 (100 mg) once daily plus PR followed by 12 or 36 weeks of treatment with PR. TMC435 is a 100-mg capsule and will be taken orally (via the mouth). Treatment with PR will last 24 or 48 weeks. Pegylated interferon is supplied as a vial containing 1.0 mL solution with 180 µg PegIFNα-2a and will be injected by a syringe under the skin once weekly. Ribavirin is given as 200-mg tablets (daily dose: 600-1000 mg), taken orally two times a day after meals. The participants will receive oral capsules of TMC435 (100 mg) once daily up to Week 12.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TMC435 100 mg 12 Wks + PR24/48 Participants will receive TMC435 100 mg once daily with PegIFNα-2a and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24 (PR 24). Treatment will be stopped at Week 24 in participants who achieve plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels less than (<) 1.2 log10 IU/mL detectable or undetectable of at Week 4, and undetectable HCV RNA levels at Week 12. All other participants will continue PR until Week 48 (PR 48). |
Drug: TMC435
100-mg capsule once daily for 12 weeks
Drug: Pegylated interferon (pegIFN alpha-2a)
180 mcg injected subcutaneously (by a syringe under the skin) once weekly for 12 to 36 weeks (or until Week 48).
Other Names:
Drug: Ribavirin (RBV)
200-mg tablets (daily dose: 600-1000 mg) taken orally (by mouth) two times a day for 12 to 36 weeks (or until Week 48).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) [Week 36 or 60]
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).
Secondary Outcome Measures
- The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) [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).
- 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 [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.
- The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT) [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]).
- The Number of Participants With Viral Breakthrough [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.
- The Number of Participants Demonstrating Viral Relapse [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.
- Plasma Concentrations of TMC435 [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 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).
- Area Under the Plasma Concentration-time Curve From 0 to 24 Hrs (AUC24h) for TMC435 [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).
- The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT) [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants must have chronic genotype 1 HCV with HCV RNA level >= 5.0 log10 IU/mL
-
Participant relapsed after previous IFN-based therapy
-
Participant must be willing to use contraceptive measures from the time of informed consent to 6 months after last dose of study medication.
Exclusion Criteria:
-
Co-infection with any other HCV genotype or co-infection with the human immunodeficiency virus (HIV)
-
Diagnosed with hepatic cirrhosis or hepatic failure
-
A medical condition which is a contraindication to pegIFN or ribavirin therapy
-
History of, or any current medical condition, which could impact the safety of the patient in the study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hiroshima | Japan | |||
| 2 | Ichikawa | Japan | |||
| 3 | Kagoshima | Japan | |||
| 4 | Matsumoto | Japan | |||
| 5 | Musashino | Japan | |||
| 6 | Ohmura | Japan | |||
| 7 | Osaka | Japan | |||
| 8 | Sapporo | Japan | |||
| 9 | Suita | Japan | |||
| 10 | Touon | Japan |
Sponsors and Collaborators
- Janssen Pharmaceutical K.K.
Investigators
- Study Director: Janssen Pharmaceutical K.K. Clinical Trial, Janssen Pharmaceutical K.K.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR017698
- TMC435HPC3008
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR 24/48 |
|---|---|
| Arm/Group Description | 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). |
| Period Title: Overall Study | |
| STARTED | 49 |
| COMPLETED | 48 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | TMC435 100 mg 12 Wks + PR 24/48 |
|---|---|
| Arm/Group Description | 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 Participants | 49 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
61
|
| Sex: Female, Male (Count of Participants) | |
| Female |
29
59.2%
|
| Male |
20
40.8%
|
Outcome Measures
| Title | The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) |
|---|---|
| Description | 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). |
| Time Frame | Week 36 or 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR24/48 |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 49 |
| Number [Percentage of participants] |
95.9
195.7%
|
| Title | The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) |
|---|---|
| Description | 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). |
| Time Frame | Week 48 or 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR24/48 |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 49 |
| Number [Percentage of participants] |
89.8
183.3%
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR24/48 |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 49 |
| Day 3 |
93.9
191.6%
|
| Day 7 |
100.0
204.1%
|
| Week 2 |
100.0
204.1%
|
| Week 3 |
98.0
200%
|
| Week 4 |
100.0
204.1%
|
| Week 8 |
100.0
204.1%
|
| Week 12 |
100.0
204.1%
|
| Week 16 |
98.0
200%
|
| Week 20 |
100.0
204.1%
|
| Week 24 |
95.9
195.7%
|
| Week 28 |
100.0
204.1%
|
| Week 36 |
93.9
191.6%
|
| Week 48 |
89.8
183.3%
|
| Week 60 |
89.8
183.3%
|
| Week 72 |
89.8
183.3%
|
| EOT |
100
204.1%
|
| FU Week 4 |
100
204.1%
|
| FU Week 12 |
95.9
195.7%
|
| FU Week 24 |
91.8
187.3%
|
| Title | The Percentage of Participants With Undetectable Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) During Treatment and at the End of Treatment (EOT) |
|---|---|
| Description | 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]). |
| Time Frame | Weeks 4, 12, 24, 36, 48, 60, 72, and at EOT |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR24/48 |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 49 |
| Week 4 |
81.6
166.5%
|
| Week 12 |
100.0
204.1%
|
| Week 24 |
95.9
195.7%
|
| Week 36 |
91.8
187.3%
|
| Week 48 |
89.8
183.3%
|
| Week 60 |
89.8
183.3%
|
| Week 72 |
89.8
183.3%
|
| EOT |
100.0
204.1%
|
| Title | The Number of Participants With Viral Breakthrough |
|---|---|
| Description | 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. |
| Time Frame | Day 1 until end of treatment (EOT [Week 24 or 48]) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR24/48 |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 49 |
| Number [Participants] |
0
0%
|
| Title | The Number of Participants Demonstrating Viral Relapse |
|---|---|
| Description | 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. |
| Time Frame | Up to 72 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR24/48 |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 49 |
| Number [Participants] |
4
8.2%
|
| Title | Plasma Concentrations of TMC435 |
|---|---|
| Description | 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). |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR24/48 |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 49 |
| C0h |
1822
|
| Cmax |
3440
|
| Title | Area Under the Plasma Concentration-time Curve From 0 to 24 Hrs (AUC24h) for TMC435 |
|---|---|
| Description | 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). |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR24/48 |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 49 |
| Median (Full Range) [ng.h/mL] |
63261
|
| Title | The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal ALT Levels at the End of Treatment (EOT) |
|---|---|
| Description | 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. |
| Time Frame | EOT (Week 24 or 48) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | TMC435 100 mg 12 Wks + PR24/48 |
|---|---|
| Arm/Group Description | 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). |
| Measure Participants | 15 |
| Number [Participants] |
11
22.4%
|
Adverse Events
| Time Frame | 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) | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | TMC435 100 mg 12 Wks + PR 24/48 | |
| Arm/Group Description | 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). | |
All Cause Mortality |
||
| TMC435 100 mg 12 Wks + PR 24/48 | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| TMC435 100 mg 12 Wks + PR 24/48 | ||
| Affected / at Risk (%) | # Events | |
| Total | 6/49 (12.2%) | |
| Gastrointestinal disorders | ||
| Nausea | 1/49 (2%) | |
| General disorders | ||
| Malaise | 1/49 (2%) | |
| Infections and infestations | ||
| Appendicitis | 1/49 (2%) | |
| Herpes zoster | 1/49 (2%) | |
| Pneumonia | 1/49 (2%) | |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||
| Breast cancer female | 1/49 (2%) | |
| Nervous system disorders | ||
| Cerebral haemorrhage | 1/49 (2%) | |
Other (Not Including Serious) Adverse Events |
||
| TMC435 100 mg 12 Wks + PR 24/48 | ||
| Affected / at Risk (%) | # Events | |
| Total | 49/49 (100%) | |
| Blood and lymphatic system disorders | ||
| Anaemia | 22/49 (44.9%) | |
| Leukopenia | 10/49 (20.4%) | |
| Neutropenia | 3/49 (6.1%) | |
| Thrombocytopenia | 3/49 (6.1%) | |
| Eye disorders | ||
| Retinal exudates | 5/49 (10.2%) | |
| Retinal haemorrhage | 3/49 (6.1%) | |
| Gastrointestinal disorders | ||
| Nausea | 10/49 (20.4%) | |
| Stomatitis | 10/49 (20.4%) | |
| Diarrhoea | 9/49 (18.4%) | |
| Constipation | 7/49 (14.3%) | |
| Abdominal discomfort | 4/49 (8.2%) | |
| Vomiting | 4/49 (8.2%) | |
| Abdominal pain upper | 3/49 (6.1%) | |
| General disorders | ||
| Pyrexia | 36/49 (73.5%) | |
| Malaise | 22/49 (44.9%) | |
| Injection site reaction | 11/49 (22.4%) | |
| Fatigue | 4/49 (8.2%) | |
| Hepatobiliary disorders | ||
| Hepatic function abnormal | 5/49 (10.2%) | |
| Hyperbilirubinaemia | 4/49 (8.2%) | |
| Infections and infestations | ||
| Nasopharyngitis | 5/49 (10.2%) | |
| Investigations | ||
| Neutrophil count decreased | 30/49 (61.2%) | |
| White blood cell count decreased | 30/49 (61.2%) | |
| Platelet count decreased | 22/49 (44.9%) | |
| Haemoglobin decreased | 20/49 (40.8%) | |
| Haematocrit decreased | 13/49 (26.5%) | |
| Red blood cell count decreased | 11/49 (22.4%) | |
| Blood triglycerides increased | 9/49 (18.4%) | |
| Blood bilirubin increased | 7/49 (14.3%) | |
| Weight decreased | 7/49 (14.3%) | |
| Blood calcium decreased | 6/49 (12.2%) | |
| Aspartate aminotransferase increased | 5/49 (10.2%) | |
| Blood alkaline phosphatase increased | 5/49 (10.2%) | |
| Blood albumin decreased | 4/49 (8.2%) | |
| Blood cholesterol decreased | 4/49 (8.2%) | |
| Blood lactate dehydrogenase increased | 4/49 (8.2%) | |
| High density lipoprotein decreased | 4/49 (8.2%) | |
| Alanine aminotransferase increased | 3/49 (6.1%) | |
| Lipase increased | 3/49 (6.1%) | |
| Monocyte percentage increased | 3/49 (6.1%) | |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 14/49 (28.6%) | |
| Hypoalbuminaemia | 4/49 (8.2%) | |
| Hypocalcaemia | 3/49 (6.1%) | |
| Musculoskeletal and connective tissue disorders | ||
| Arthralgia | 20/49 (40.8%) | |
| Myalgia | 13/49 (26.5%) | |
| Back pain | 8/49 (16.3%) | |
| Musculoskeletal stiffness | 3/49 (6.1%) | |
| Nervous system disorders | ||
| Headache | 25/49 (51%) | |
| Dysgeusia | 5/49 (10.2%) | |
| Dizziness | 3/49 (6.1%) | |
| Psychiatric disorders | ||
| Insomnia | 5/49 (10.2%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 6/49 (12.2%) | |
| Oropharyngeal pain | 4/49 (8.2%) | |
| Skin and subcutaneous tissue disorders | ||
| Pruritus | 19/49 (38.8%) | |
| Alopecia | 17/49 (34.7%) | |
| Rash | 16/49 (32.7%) | |
| Dry skin | 8/49 (16.3%) | |
| Eczema | 5/49 (10.2%) | |
| Erythema | 3/49 (6.1%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Manager |
|---|---|
| Organization | Janssen Pharmaceutical K.K., Japan |
| Phone | 81 3 44115639 |
- CR017698
- TMC435HPC3008