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| ID | Type | Description | Link |
|---|---|---|---|
| TMC435HPC3010 | Other Identifier | Janssen Pharmaceutical K.K., Japan |
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The purpose of this study is to evaluate the efficacy and safety of TMC435 in combination with peginterferon alfa-2b and ribavirin in chronic genotype 1 hepatitis C virus (HCV)-infected participants who are treatment-naive or treatment-experienced (prior relapser or non-responder to Interferon-based therapy) in Japan.
This is an open-label study (all people involved know the identity of the intervention) to evaluate the efficacy and safety of TMC435 (also referred to as jnj-38733214-aaa) in combination with the standard of care therapy (SoC: peginterferon [pegIFN] alfa-2b and ribavirin) in adult, genotype 1 hepatitis C virus (HCV)-infected participants who are treatment-naive (never received treatment for HCV), prior relapsers (relapsed after previous interferon [IFN]-based therapy), or non-responders (failed to respond to previous IFN-based therapy) in Japan. The study objective is to evaluate the efficacy, safety, and pharmacokinetics of TMC435. A sufficient number of participants who are treatment-naive, prior relapsers to treatment with IFN-based therapy, and prior non-responders to treatment with IFN-based therapy will be enrolled and assigned to 1 of 3 panels (referred to as treatment groups). Participants who are treatment-naive or prior relapsers to IFN-based therapy will receive 12 weeks of treatment with TMC435 (100 mg) once daily with pegIFN alfa-2b and ribavirin (PR) followed by an additional 12 or 24 weeks of treatment with PR. Participants who are non-responders to IFN-based therapy will receive 12 weeks of treatment with TMC435 (100 mg) once daily with PR followed by an additional 36 weeks of treatment with PR. TMC435 is a 100-mg capsule and will be taken orally by mouth. The SoC treatment will consist of Pegylated interferon (PegIFN alpha-2b) (1.5 mcg/kg) injected with a syringe subcutaneously (under the skin) once weekly and ribavirin 200-mg capsules (daily dose: 600-1000 mg based on body weight) taken orally by mouth 2 times a day after meals for 24 or 48 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | Experimental | Participants will receive TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks), followed by PR until Week 24 or Week 48. Treatment will be stopped at Week 24 in participants who achieve 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 will continue PR until Week 48. |
|
| Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | Experimental | Participants will receive TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 24. Treatment will be stopped at Week 24 in participants who achieve 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 will continue PR until Week 48. |
|
| Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | Experimental | Participants will receive TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TMC435 | Drug | 100 mg capsule taken by mouth once daily for 12 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) | The table below shows the percentage of participants in each treatment group with an SVR12 defined as participants with undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma HCV RNA 12 weeks after the last dose of treatment (Week 36 or 60). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | Week 36 or 60 |
| The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) | The table below shows the percentage of participants in each treatment group with a SVR24 defined as participants with undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment and at 24 weeks after the last dose of treatment (Week 48 or 72). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 24 weeks after the last dose of treatment (Week 48 or 72) |
| The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During Treatment and at the End of Treatment | The table below shows the percentage of participants in each treatment group with undetectable HCV RNA less than 1.2 log10 IU/mL during treatment and at end of treatment (EOT). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | Weeks 4, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48) |
| The Number of Participants With Viral Breakthrough | The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period. Viral breakthrough is defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA of greater than 2.0 log10 IU/mL in participants whose plasma HCV RNA level had previously been reported below 1.2 log10 IU/mL detectable or undetectable. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Pharmaceutical K.K. Clinical Trial | Janssen Pharmaceutical K.K. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amagasaki | Japan | |||||
Participants with genotype 1 hepatitis C virus (HCV) infection who were treatment-naïve or treatment-experienced (prior relapsers or nonresponders to interferon-based therapy) were assigned to 1 of 3 groups and received TMC435 100 mg/day for 12 weeks coadministered with PegIFNa-2b + ribavirin until Week 24 or Week 48.
The study was conducted between 01-Apr-2011 to 20-Nov-2012 and recruited participants with chronic Hepatitis C Virus (HCV) infection from 14 study centers in Japan. A total of 79 participants with chronic genotype 1 HCV infection were randomized and started treatment; 65 completed the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks), followed by PR until Week 24 or Week 48. 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. |
| FG001 | Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 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. |
| FG002 | Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks), followed by PR until Week 24 or Week 48. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Percentage of Participants With a Sustained Virologic Response 12 Weeks After the Actual End of Treatment (SVR12) | The table below shows the percentage of participants in each treatment group with an SVR12 defined as participants with undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment (Week 24 or 48) who also had undetectable plasma HCV RNA 12 weeks after the last dose of treatment (Week 36 or 60). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Number | Percentage of Participants | Week 36 or 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)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment-Naive: TMC435 100 mg 12 Wks+PR 24/48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks), followed by PR until Week 24 or Week 48. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA Version 15.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA Version 15.0 | Non-systematic Assessment |
All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated. "Primary" was chosen for each outcome measure because "Exploratory" is not available as an outcome measure type on this form.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Director | Janssen Pharmaceutical K.K., Japan | 81 3 44115639 |
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| ID | Term |
|---|---|
| D019698 | Hepatitis C, Chronic |
| D006526 | Hepatitis C |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
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| ID | Term |
|---|---|
| D000069616 | Simeprevir |
| C417083 | peginterferon alfa-2b |
| D012254 | Ribavirin |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Peginterferon alfa-2b (pegIFN alfa-2b) | Drug | PegIFN alfa-2b will be supplied as a vial containing dried and frozen powder with 74,148 or 222 mcg pegIFN alpha-2b attached to 0.7 ml injection water (50, 100 or 150 mcg/0.5mL pegIFN alpha-2b) and will be administered according to the manufacturer's prescribing information as 1.5 mcg/kg once weekly injected subcutaneous (under the skin) for up to 24-48 weeks. |
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| Ribavirin (RBV) | Drug | The dose of RBV given will be based on body weight. If body weight is > 80 kg the total daily dose of RBV will be 1000 mg, taken by mouth as 400 mg (2 capsules of 200 mg) after breakfast and 600 mg (3 capsules of 200 mg) after supper. If body weight is > 60 kg to <=80 kg the total daily dose will be 800 mg, taken by mouth as 400 mg (2 capsules of 200 mg per intake) after breakfast and supper. If body weight is <=60 kg the total daily dose of RBV will be 600 mg, taken by mouth as 200 mg (1 capsule of 200 mg) after breakfast and 400 mg (2 capsules of 200 mg) after supper. Total duration of RBV will be 24-48 weeks. |
|
|
| Up to 48 Weeks |
| The Number of Participants Demonstrating Viral Relapse | The table below shows the number of participants in each treatment group who demonstrated viral relapse, defined as having undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at end of treatment (EOT [Week 24 or 48]) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of an assessment of sustained virologic response (SVR). The number of participants analyzed in each treatment group below are those with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | Up to 72 weeks |
| The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at the End of Treatment (EOT) | The table below shows the number of participants in each treatment group with abnormal ALT levels at Baseline who achieved normalization of ALT levels defined as having an ALT value less than or equal to the Upper Limit of Normality (ie, 40 IU/mL) at EOT. At Baseline, 15 treatment-naïve participants, 13 prior relapsers, and 13 prior non-responders had abnormal ALT levels at Baseline. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | Up to Week 48 |
| The Percentage of Participants Who Achieved a Greater Than or Equal to 2 log10 IU/mL Drop From Baseline in Plasma Hepatitis C Virus Ribonucleic Acid (HCV RNA) at Each Time Point During Treatment and Follow-up | The table below shows the percentage of participants in each treatment group with greater than or equal to 2 log10 IU/mL drop from baseline in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at each time point during treatment and post-treatment follow-up. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | Day 3, Day 7 and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT (up to Week 24 or 48), follow-up (FU) Week 4, 12, and 24 |
| The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2b (PegIFNα-2b) and Ribavirin (RBV) at Week 24 | The table below shows the percentage of participants in each treatment group who met RGT criteria (ie, who had plasma levels of hepatitis C virus ribonucleic acid [HCV RNA] <1.2 log10 IU/mL detectable/undetectable at Week 4 and <1.2 log 10 IU/mL undetectable at Week 12) and completed treatment with PegIFNα-2b and RBV at Week 24. Participants in the TMC435 Treatment-Naïve and TMC435 Prior Relapser treatment groups not meeting RGT criteria continued treatment with PegIFNα-2a and RBV to Week 48 (does not apply to the TMC435 Non-responder treatment group because the specified treatment duration was 48 weeks and RGT criteria was not assessed at Week 24). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | Week 24 or 48 |
| The Area Under the Plasma Concentration-Time Curve (From 0 to 24 Hours) (AUC24h) | The table below shows the median (range) AUC24h values for TMC435 for all participants in each TMC435 treatment group who received TMC435 for up to 12 weeks. "Overall" is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | Overall (Up to Week 12) |
| Plasma Concentrations of TMC435 | The table below shows the median (range) TMC435 predose plasma concentrations (C0h) and maximum concentration (Cmax) values for participants in each treatment group. "Overall" is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | Overall (Up to Week 12) |
| Ikeda |
| Japan |
| Kawasaki | Japan |
| Kumamoto | Japan |
| Niigata | Japan |
| Ohmura | Japan |
| Osaka | Japan |
| Sakai | Japan |
| Sapporo | Japan |
| Suita | Japan |
| Tokyo | Japan |
| BG001 | Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 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. |
| BG002 | Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48. |
| BG003 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks), followed by PR until Week 24 or Week 48. 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. |
| OG001 | Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 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. |
| OG002 | Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48. |
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| Primary | The Percentage of Participants With a Sustained Virologic Response 24 Weeks After the Actual End of Treatment (SVR24) | The table below shows the percentage of participants in each treatment group with a SVR24 defined as participants with undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at the end of treatment and at 24 weeks after the last dose of treatment (Week 48 or 72). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Number | Percentage of participants | 24 weeks after the last dose of treatment (Week 48 or 72) |
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| Primary | The Percentage of Participants With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During Treatment and at the End of Treatment | The table below shows the percentage of participants in each treatment group with undetectable HCV RNA less than 1.2 log10 IU/mL during treatment and at end of treatment (EOT). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Number | Percentage of participants | Weeks 4, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48) |
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| Primary | The Number of Participants With Viral Breakthrough | The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period. Viral breakthrough is defined as a confirmed increase of greater than 1 log10 IU/mL in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA of greater than 2.0 log10 IU/mL in participants whose plasma HCV RNA level had previously been reported below 1.2 log10 IU/mL detectable or undetectable. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Number | Participants | Up to 48 Weeks |
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| Primary | The Number of Participants Demonstrating Viral Relapse | The table below shows the number of participants in each treatment group who demonstrated viral relapse, defined as having undetectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels at end of treatment (EOT [Week 24 or 48]) and detectable HCV RNA during follow-up or detectable HCV RNA at the time points of an assessment of sustained virologic response (SVR). The number of participants analyzed in each treatment group below are those with undetectable HCV RNA levels at EOT and with at least one follow-up HCV RNA measurement. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Number | Participants | Up to 72 weeks |
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| Primary | The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normal Limit of ALT at the End of Treatment (EOT) | The table below shows the number of participants in each treatment group with abnormal ALT levels at Baseline who achieved normalization of ALT levels defined as having an ALT value less than or equal to the Upper Limit of Normality (ie, 40 IU/mL) at EOT. At Baseline, 15 treatment-naïve participants, 13 prior relapsers, and 13 prior non-responders had abnormal ALT levels at Baseline. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Number | Percentage of participants | Up to Week 48 |
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| Primary | 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 | The table below shows the percentage of participants in each treatment group with greater than or equal to 2 log10 IU/mL drop from baseline in plasma hepatitis C virus (HCV) ribonucleic acid (RNA) at each time point during treatment and post-treatment follow-up. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Number | Percentage of participants | Day 3, Day 7 and Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 36, 48, 60, 72, EOT (up to Week 24 or 48), follow-up (FU) Week 4, 12, and 24 |
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| Primary | The Percentage of Participants Who Met Response Guided Treatment (RGT) Criteria and Completed Treatment With Peginterferon Alpha-2b (PegIFNα-2b) and Ribavirin (RBV) at Week 24 | The table below shows the percentage of participants in each treatment group who met RGT criteria (ie, who had plasma levels of hepatitis C virus ribonucleic acid [HCV RNA] <1.2 log10 IU/mL detectable/undetectable at Week 4 and <1.2 log 10 IU/mL undetectable at Week 12) and completed treatment with PegIFNα-2b and RBV at Week 24. Participants in the TMC435 Treatment-Naïve and TMC435 Prior Relapser treatment groups not meeting RGT criteria continued treatment with PegIFNα-2a and RBV to Week 48 (does not apply to the TMC435 Non-responder treatment group because the specified treatment duration was 48 weeks and RGT criteria was not assessed at Week 24). NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Number | Percentage of participants | Week 24 or 48 |
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| Primary | The Area Under the Plasma Concentration-Time Curve (From 0 to 24 Hours) (AUC24h) | The table below shows the median (range) AUC24h values for TMC435 for all participants in each TMC435 treatment group who received TMC435 for up to 12 weeks. "Overall" is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Median | Full Range | ng·h/mL | Overall (Up to Week 12) |
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| Primary | Plasma Concentrations of TMC435 | The table below shows the median (range) TMC435 predose plasma concentrations (C0h) and maximum concentration (Cmax) values for participants in each treatment group. "Overall" is the median exposure estimate using all available data for each participant in the study. NOTE: All outcome measures reported in this study are "Exploratory;" not "Primary" as indicated (refer to Limits and Caveats). | 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. | Posted | Median | Full Range | ng/mL | Overall (Up to Week 12) |
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| 1 |
| 24 |
| 24 |
| 24 |
| EG001 | Prior Relapser: TMC435 100 mg 12 Wks+PR 24/48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 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. | 0 | 29 | 29 | 29 |
| EG002 | Prior Non-Responder: TMC435 100 mg 12 Wks+PR 48 | Participants received TMC435 100 mg once daily with PegIFNa-2b and ribavirin (PR) for 12 weeks (Wks) followed by PR until Week 48. | 1 | 26 | 26 | 26 |
| Peripheral T-cell lymphoma unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 15.0 | Non-systematic Assessment |
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| Malaise | General disorders | MedDRA Version 15.0 | Non-systematic Assessment |
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| Injection site reaction | General disorders | MedDRA Version 15.0 | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA Version 15.0 | Non-systematic Assessment |
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| Injection site erythema | General disorders | MedDRA Version 15.0 | Non-systematic Assessment |
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| Chills | General disorders | MedDRA Version 15.0 | Non-systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
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| Platelet count decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
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| Haematocrit decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
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| Red blood cell count decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
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| Blood albumin decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
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| Blood calcium decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
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| Blood cholesterol decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Lymphocyte percentage increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Bilirubin conjugated increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Blood bilirubin unconjugated increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Eosinophil percentage increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| High density lipoprotein decreased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Lipase increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Monocyte percentage increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Liver function test abnormal | Investigations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Heat rash | Skin and subcutaneous tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Cheilitis | Gastrointestinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA Version 15.0 | Non-systematic Assessment |
|
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.
| D014777 |
| Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006575 |
| Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D012263 | Ribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| Title | Measurements |
|---|---|
|
| Week 24 |
|
| Week 36 |
|
| Week 48 |
|
| Week 60 |
|
| Week 72 |
|
| EOT |
|
| Title | Measurements |
|---|---|
|
| Week 2 |
|
| Week 3 |
|
| Week 4 |
|
| Week 8 |
|
| Week 12 |
|
| Week 16 |
|
| Week 20 |
|
| Week 24 |
|
| Week 28 |
|
| Week 36 |
|
| Week 48 |
|
| Week 60 |
|
| Week 72 |
|
| EOT |
|
| FU Week 4 |
|
| FU Week 12 |
|
| FU Week 24 |
|
|