Hepatitis C, Chronic
Conditions
Keywords
Hepatitis C, Chronic, Tibotec, TMC435350-TiDP16-C201, TMC435350-C201, TMC435, PEGASYS (peginterferon alpha-2a, PegIFNα-2a), COPEGUS (ribavirin)
Brief summary
The purpose of this study is to investigate how efficient TMC435350 will work against the Hepatitis C virus genotype 1 (genotypes refer to the genetic constitution of the virus) and what the concentrations of TMC435350 in the blood are with or without pegylated interferon alpha-2a (PegIFNa-2a) or PegIFNa-2a plus ribavirin.
Detailed description
This is a blinded (participant and study staff will not know the identity of assigned treatments), randomized (participants assigned to treatment by chance), placebo-controlled (a term used to describe a method of research in which an inactive substance referred to as a placebo is given to one group of participants, while the treatment being tested is given to another group) study to assess the effectiveness, safety, tolerability, and pharmacokinetics (to test the concentration of study drug in the blood over time) of different dose regimens of TMC435350 (hereafter referred to as TMC435) given alone or in combination with peginterferon alpha-2a (PegIFNa-2a) and ribavirin. TMC435 is a new drug that is development for the treatment of Hepatitis C virus (HCV) infection and belongs to a class of drugs that work by blocking an enzyme (protease) that the HCV needs to replicate. The combination of PegIFNa-2a and ribavirin are current standard of care (SoC) therapy for patients with chronic HCV infection. Approximately 72 participants with HCV infection who have never been treated for HCV infection (referred to as treatment-naïve participants) and 36 participants who have been treated for HCV infection (referred to as treatment-experienced participants) who did not respond to previous therapy with interferon (IFN) and who did not discontinue previous anti-HCV therapy because of adverse events \[AEs\]) will be included in this study. Two blinded placebo-controlled groups (referred to as cohorts) of treatment-naïve participants will be sequentially initiated TMC435 to ensure that a higher dose is only administered if the previous lower dose is found safe and tolerable. The first group (Cohort 1) of treatment-naïve participants will receive low-doses of TMC435 or placebo for 7 days followed by 21 days of combined tritherapy with PegIFNa-2a and ribavirin OR participants will receive 28 days of tritherapy (TMC435 or placebo + PegIFNa-2a and ribavirin). After review of data from Cohort 1, a second group (Cohort 2) of treatment-naïve participants will be given higher doses of TMC435 or placebo in the same manner described for the first cohort. A third group (Cohort 3) of participants previously planned in the study will not be enrolled. After review of data from Cohort 2, a fourth group (Cohort 4) of treatment-experienced participants will be given 28 days of TMC435 (or placebo) as tritherapy with PegIFNa-2a and ribavirin to determine the maximum tolerated dose of TMC435. In addition, up to 10 HCV-infected individuals (who participated in study TMC435350-TiDP16-C101 (ClinicalTrials.gov registry number NCT00938899) will comprise Cohort 5 and will be given 28 days of TMC435 at a dose previously determined to be safe and efficacious as tritherapy with PegIFNa-2a and ribavirin. Blood samples will be taken from participants at protocol-specified time points to determine plasma concentrations of TMC435 and ribavirin and safety will be monitored throughout the study. Individuals will participate in this study for up 54 weeks (includes up to 6 weeks during the screening period followed by up to 4 weeks of study treatment with TMC435 (or placebo) and up to a maximum of 44 weeks of treatment with PegIFNa-2a and ribavirin.
Interventions
DRUGTMC435
TMC435 25 mg, 75 mg, 150 mg, or 200 mg capsules taken orally (by mouth) once daily for 21 or 28 days.
DRUGPlacebo
Placebo capsules identical in appearance to TMC435 capsules taken orally (by mouth) once daily for 28 days.
DRUGPeginterferon (PegIFNα-2a)
One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFNα-2a on Days 1, 8, 15, and 22
DRUGRibavirin
200-mg tablets of ribavirin (body-weight adjusted dose) taken orally (by mouth) twice daily for 21 or 28 days in Cohorts 1 and 2 and for 28 days in Cohorts 4 and 5.
Sponsors
Tibotec Pharmaceuticals, Ireland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
- Documented chronic genotype 1 Hepatitis C infection - Able to comply with the protocol requirements and having good accessible veins - Amount of virus in the blood (HCV RNA) \>= 10.000 IU/mL, at screening - Bodyweight as defined by a Quetelet Index (Body Mass Index \[BMI\]) between 18 and 32 kg/m², extremes included
Exclusion criteria
- Evidence of liver cirrhosis or decompensated liver disease or any other form of non-viral hepatitis - Participants receiving or having received treatment with polymerase inhibitor or protease inhibitor, or Standard of Care therapy with COPEGUS (ribavirin) and PEGASYS (peginterferon alpha-2a) for treatment for HCV during the 6 months before screening - Male participants with female partners of childbearing potential not agreeing to use a reliable birth control method, Female, except if postmenopausal for over 2 years, or posthysterectomy, or post-tubal ligation (without reversal operation) - History or evidence of current use of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, which would compromise the participant 's safety and/or compliance. A positive urine drug test at screening. Urine will be tested to check the current use of amphetamines, cocaine, and opioids (with the exclusion of methadone) - Participants having at least one lab toxicity that is found to be clinically significant - Participants co-infected with HIV, or Hepatitis A or B, or hepatitis B surface antigen, or active tuberculosis at screening, participants with prolonged QTc (\>480 ms) value or any cardiac disease at screening, or any active clinically significant disease (e.g., cardiac dysfunction, cardio(myo)pathy, cardiac insufficiency), or medical history or physical examination findings during screening that, in the Investigator's opinion, would compromise the outcome of the trial - Participants having uncontrolled/unstable diabetes, epilepsy, a manifest psychiatric disease, non-stable methadone (or equivalent drug) use or participants having any other unstable disease, participants enrolled in another clinical trial within 90 days prior to screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | Week 4 | The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo as for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection). |
| Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | Week 4 | The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection). |
| Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Week 4 | The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon \[IFN\]-based therapy \[pegylated or non-pegylated\]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2 or 3, Day 7, and Day 28 | The table below shows the number of treatment-naïve HCV-infected participants treated with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 who had the following virologic responses: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than \[\<\] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, \<25 IU/mL undetectable); plasma levels of HCV RNA \<100 IU/mL; and plasma levels of HCV RNA \<1000 at the time points listed. See treatment-naive defined above. |
| Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2 or 3, Day 7, and Day 28 | The table below shows the number of treatment-naive HCV-Infected participants with the following virologic responses to treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than \[\<\] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, \<25 IU/mL undetectable); plasma levels of HCV RNA \<100 IU/mL; and plasma levels of HCV RNA \<1000 at the time points listed. See treatment-naive defined above. |
| Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2 or 3, Day 7, and Day 28 | The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with the following virologic responses to treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than \[\<\] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, \<25 IU/mL undetectable); plasma levels of HCV RNA \<100 IU/mL; and plasma levels of HCV RNA \<1000 at the time points listed. Note: in the table below, the number of participants (n) analyzed in the TMC435 200 mg (Cohort 4, Panel B) on Day 28 (Week 4) was n=4. |
| Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR) | The table below shows the number of treatment-naïve participants in the treatment groups for Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined) who met the following virologic response parameters: rapid virological response (RVR) defined as having undetectable plasma HCV ribonucleic acid (RNA) at Week 4; early virologic response (EVR) defined as change from baseline in plasma HCV RNA of greater than or equal to 2 log 10 at Week 12); a complete EVR (cEVR) defined as a complete EVR having undetectable plasma HCV RNA at Week 12); an extended RVR (eRVR) defined as undetectable plasma HCV RNA at Week 4 and 12; and a partial response defined as EVR but not reaching undetectability while on treatment. |
| Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR) | The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 who met the following virologic response parameters: rapid virological response (RVR) defined as having undetectable plasma HCV ribonucleic acid (RNA) at Week 4; early virologic response (EVR) defined as change from baseline in plasma HCV RNA of greater than or equal to 2 log 10 at Week 12; a complete EVR (cEVR) defined as a EVR having undetectable plasma HCV RNA at Week 12; an extended RVR (eRVR) defined as undetectable plasma HCV RNA at Week 4 and 12; and a partial response defined as EVR but not reaching undetectability while on treatment. |
| Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2 or 3 | The table below shows the number of treatment-naïve participants with an initial suboptimal response defined as less than 2 log10 change in plasma level of hepatitis C virus (HCV) ribonucleic acid (RNA) on Day 2 or 3 (depending when visit was scheduled) following treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22. See treatment-naive defined above. |
| Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2 or 3 | The table below shows the number of treatment-naïve participants with an initial suboptimal response defined as less than 2 log10 change in plasma plasma level of hepatitis C virus (HCV) ribonucleic acid (RNA) on Day 2 or 3 (depending when visit was scheduled) after treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. See treatment-naive defined above. |
| Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2 or 3 | The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with an initial suboptimal response defined as less than 2 log10 change of plasma in plasma level of HCV ribonucleic acid (RNA) at Day 2 or 3 (depending when visit was scheduled) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. |
| Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | 4 Weeks (Wks), 44 Wks, and 48 Wks | The table below shows the number of treatment-naïve participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached, or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (less than 25 IU/mL undetectable) after treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on days 8, 15, and 22 (Panel A) and after treatment with TMC435 or placebo coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). |
| Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 4 Weeks (Wks), 44 Wks, and 48 Wks | The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (less than 25 IU/mL undetectable) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. |
| Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Up to Week 72 | The table below shows the number of treatment-naïve participants with viral relapse (defined as having confirmed detectable plasma level of HCV ribonucleic acid \[RNA\] during the follow-up period in participants with undetectable plasma HCV RNA \[less than 25 IU/mL undetectable\] at the end of treatment) for the treatment groups in Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined). See treatment-naïve defined above. |
| Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | Day 7 | The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (at Week 1) following treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection). |
| Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72) | The table below shows the number of treatment-naïve participants with an SVR to treatment (defined as having an undetectable plasma level of HCV ribonucleic acid after the last planned dose of treatment) for the treatment groups in Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined). SVR was measured at 4, 8, 12, and 24 weeks after the last dose of treatment (SVR4, SVR8, SVR12, and SVR24, respectively). See treatment-naïve defined above. |
| Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72) | The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) in each treatment group in Cohort 4, Panel C and in Cohort 5, Panel D with an SVR to treatment defined as having an undetectable plasma level of HCV ribonucleic acid after the last planned dose of the entire treatment regimen. SVR was measured at 4, 8, 12, and 24 weeks after the last dose of treatment (SVR4, SVR8, SVR12, and SVR24, respectively). |
| Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) | The table below shows the mean (standard deviation) Cmax for treatment-naïve participants at selected time points who were treated with TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). See treatment-naïve defined above. The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10. |
| Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) | The table below shows the mean (standard deviation) Cmax for treatment-experienced participants (non-responders and relapsers, see defined above) following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 28 in the 4 treatment groups listed below from left to right were 8, 8, 10, and 3. |
| Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) | The table below shows mean (standard deviation) of C0h of TMC435 at selected time points following treatment with TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) or with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B) in treatment-naïve participants (see treatment-naïve defined above).The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 9, 8, 9, 9, and 10. |
| Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) | The table below shows mean (standard deviation) of C0h for treatment-experienced participants (non-responders and relapsers, see defined above) following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 2 and Day 28 differed as follows: At Day 2, the number of participants in the 4 treatment groups (from left to right) were 8, 7, 10, and 5; the number of participants analyzed at Day 28 in the 4 treatment groups (from left to right) were 9, 8, 10, and 4. |
| Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 7 (predose); Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel A, Cohorts 1 and 2) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel B, Cohorts 1 and 2) | The table below shows mean (standard deviation)of Css,av for TMC435 in treatment-naïve HCV-infected participants at selected time points administered TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). See treatment-naïve defined above. The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10. |
| Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) | The table below shows mean (standard deviation) of Css,av for TMC435 in treatment-experienced HCV-infected participants (non-responders and relapsers, see defined above) at selected time points following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. |
| Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) | The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 in treatment-naïve HCV-infected participants administered TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B).The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10. |
| Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) | The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 in treatment-experienced HCV-infected participants considered non-responders (participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV ribonucleic acid (RNA) levels after 12 weeks of previous interferon \[IFN\]-based therapy \[pegylated or non-pegylated\]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up at selected time points following treatment with TMC435 coadministered with ribavirin (RBV) for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 28 in the 4 treatment groups listed below from left to right was 8, 7, 10, and 3. |
| Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Up to Week 72 | The table below shows the number of treatment-experienced participants combined (non-responders and relapsers, see defined above) with viral relapse, defined as having confirmed detectable plasma level of HCV ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment who received TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. |
| Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | Day 7 | The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (at Week 1) following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants (A treatment-naive participant is someone who has never taken drugs for their HCV infection). |
| Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7 | The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (Week 1) following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon \[IFN\]-based therapy \[pegylated or non-pegylated\]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up). |
Countries
Belgium, France, Germany, Netherlands, Poland, United Kingdom
Participant flow
Recruitment details
The study was conducted at 25 sites in 6 countries: Belgium, France, Germany, Poland, the Netherlands, and the United Kingdom.
Pre-assignment details
A total of 121 participants infected with Hepatitis C virus (HCV) were randomized of whom 116 were treated. Reasons for not receiving treatment were withdrawal of consent (4 participants) and sponsor's decision (1 participant).
Participants by arm
| Arm | Count |
|---|---|
| TMC435 25 mg (Cohort 1) Treatment-naïve participants received TMC435 25 mg once daily for 7 days followed by TMC435 25 mg once daily coadministered with ribavirin (RBV) for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) OR TMC435 25 mg once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B) | 18 |
| TMC435 75mg (Cohort 1) Treatment-naïve participants received TMC435 75 mg once daily for 7 days followed by TMC435 75 mg once daily coadministered with RBV for 21 days + PegIFNα-2a on Days 8, 15, and 22 (Panel A) OR TMC435 75 mg once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B) | 19 |
| Placebo (Cohort 1) Treatment-naïve participants received placebo (identical in appearance to TMC435 25 mg or 75 mg) once daily for 7 days followed by placebo once daily coadministered with RBV for 21 days + PegIFNα-2a on Days 8, 15, and 22 (Panel A) OR placebo once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B) | 13 |
| TMC435 200 mg (Cohort 2) Treatment-naïve participants received TMC435 200 mg once daily for 7 days followed by TMC435 200 mg once daily coadministered with RBV for 21 days + PegIFNα-2a on Days 8, 15, and 22 (Panel A) OR TMC435 200 mg once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B) | 18 |
| Placebo (Cohort 2) Treatment-naïve participants received placebo (identical in appearance to TMC435 200 mg) once daily for 7 days followed by placebo once daily coadministered with RBV for 21 days + PegIFNα-2a on Days 8, 15, and 22 (Panel A) OR placebo once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B) | 6 |
| TMC435 75 mg (Cohort 4) Treatment-experienced non-responders received TMC435 75 mg once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22. | 9 |
| TMC435 150 mg (Cohort 4) Treatment-experienced non-responders received TMC435 150 mg once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22. | 9 |
| TMC435 200 mg (Cohort 4) Treatment-experienced non-responders received TMC435 200 mg once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22. | 10 |
| Placebo (Cohort 4) Treatment-experienced non-responders received placebo (identical in appearance to TMC435 75 mg, 150 mg, or 200 mg) once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22. | 9 |
| TMC435 200 mg (Cohort 5) Treatment-experienced relapsers received TMC435 200 mg once daily coadministered with RBV for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22. | 5 |
| Total | 116 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 1 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Subject ineligible to continue the trial | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 1 |
| Overall Study | Subject reached a virologic endpoint | 2 | 1 | 1 | 4 | 1 | 3 | 4 | 4 | 5 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | TMC435 25 mg (Cohort 1) | TMC435 75mg (Cohort 1) | Placebo (Cohort 1) | TMC435 200 mg (Cohort 2) | Placebo (Cohort 2) | TMC435 75 mg (Cohort 4) | TMC435 150 mg (Cohort 4) | TMC435 200 mg (Cohort 4) | Placebo (Cohort 4) | TMC435 200 mg (Cohort 5) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 52 years | 47 years | 45 years | 46.5 years | 44.5 years | 53 years | 56 years | 55.5 years | 47 years | 56 years | 49 years |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 3 Participants | 8 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 31 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 10 Participants | 10 Participants | 5 Participants | 6 Participants | 8 Participants | 8 Participants | 9 Participants | 5 Participants | 85 Participants |
| The Number of Participants Randomized to each Treatment Panel Panel A | 9 participants | 10 participants | 6 participants | 9 participants | 3 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 37 participants |
| The Number of Participants Randomized to each Treatment Panel Panel B | 9 participants | 9 participants | 7 participants | 9 participants | 3 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 37 participants |
| The Number of Participants Randomized to each Treatment Panel Panel C | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 9 participants | 9 participants | 10 participants | 9 participants | 0 participants | 37 participants |
| The Number of Participants Randomized to each Treatment Panel Panel D | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 5 participants | 5 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 18 | 19 / 19 | 13 / 13 | 18 / 18 | 6 / 6 | 8 / 9 | 9 / 9 | 10 / 10 | 9 / 9 | 5 / 5 | 87 / 88 |
| serious Total, serious adverse events | 2 / 18 | 3 / 19 | 3 / 13 | 3 / 18 | 0 / 6 | 1 / 9 | 1 / 9 | 2 / 10 | 0 / 9 | 1 / 5 | 13 / 88 |
Outcome results
Primary
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon \[IFN\]-based therapy \[pegylated or non-pegylated\]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up).
Time frame: Week 4
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -4.28 log10 IU/mL | Standard Error 0.539 |
| TMC435 75 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -5.46 log10 IU/mL | Standard Error 0.425 |
| Placebo (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -5.26 log10 IU/mL | Standard Error 0.238 |
| TMC435 200 mg (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -1.53 log10 IU/mL | Standard Error 0.216 |
| Placebo (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -5.86 log10 IU/mL | Standard Error 0.198 |
Primary
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo as for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Time frame: Week 4
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | -4.26 log10 IU/mL | Standard Error 0.646 |
| TMC435 75 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | -4.47 log10 IU/mL | Standard Error 0.489 |
| Placebo (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | -2.97 log10 IU/mL | Standard Error 0.64 |
| TMC435 200 mg (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | -4.70 log10 IU/mL | Standard Error 0.584 |
| Placebo (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | -1.92 log10 IU/mL | Standard Error 0.156 |
Primary
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the change from Baseline in plasma levels of HCV RNA at Week 4 following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Time frame: Week 4
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -4.74 log10 IU/mL | Standard Error 0.455 |
| TMC435 75 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -5.52 log10 IU/mL | Standard Error 0.228 |
| Placebo (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -3.74 log10 IU/mL | Standard Error 0.665 |
| TMC435 200 mg (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -5.44 log10 IU/mL | Standard Error 0.169 |
| Placebo (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) at Week 4 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -3.26 log10 IU/mL | Standard Error 1.222 |
Secondary
Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 in treatment-naïve HCV-infected participants administered TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B).The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10.
Time frame: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Population: All participants who received treatment were included in the pharmacokinetic (PK) analysis, however, due to various reasons (ie, missing samples at certain time points, or exclusion of specific plasma concentrations from the PK analysis) not all PK parameters could always be calculated for each participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 3035 ng.h/mL | Standard Deviation 1205 |
| TMC435 25 mg (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 3961 ng.h/mL | Standard Deviation 1523 |
| TMC435 75 mg (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 12240 ng.h/mL | Standard Deviation 5663 |
| TMC435 75 mg (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 16600 ng.h/mL | Standard Deviation 10680 |
| Placebo (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 167200 ng.h/mL | Standard Deviation 154500 |
| Placebo (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 43430 ng.h/mL | Standard Deviation 22280 |
| TMC435 200 mg (Cohort 2, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 2853 ng.h/mL | Standard Deviation 1207 |
| TMC435 200 mg (Cohort 2, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 4527 ng.h/mL | Standard Deviation 2806 |
| Placebo (Cohort 2, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 23610 ng.h/mL | Standard Deviation 26780 |
| Placebo (Cohort 2, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 12790 ng.h/mL | Standard Deviation 7888 |
| TMC435 200 mg (Cohort 2, Panel B) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 45700 ng.h/mL | Standard Deviation 24160 |
| TMC435 200 mg (Cohort 2, Panel B) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 169400 ng.h/mL | Standard Deviation 126500 |
Secondary
Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 in treatment-experienced HCV-infected participants considered non-responders (participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV ribonucleic acid (RNA) levels after 12 weeks of previous interferon \[IFN\]-based therapy \[pegylated or non-pegylated\]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up at selected time points following treatment with TMC435 coadministered with ribavirin (RBV) for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 28 in the 4 treatment groups listed below from left to right was 8, 7, 10, and 3.
Time frame: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Population: All participants who received treatment were included in the pharmacokinetic (PK) analysis, however, due to various reasons (ie, missing samples at certain time points, or exclusion of specific plasma concentrations from the PK analysis) not all PK parameters could always be calculated for each participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 1 | 11150 ng.h/mL | Standard Deviation 2903 |
| TMC435 25 mg (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 20150 ng.h/mL | Standard Deviation 14720 |
| TMC435 75 mg (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 57440 ng.h/mL | Standard Deviation 44730 |
| TMC435 75 mg (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 1 | 30920 ng.h/mL | Standard Deviation 13450 |
| Placebo (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 1 | 34410 ng.h/mL | Standard Deviation 14440 |
| Placebo (Cohort 1, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 152600 ng.h/mL | Standard Deviation 126600 |
| TMC435 200 mg (Cohort 2, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 1 | 51300 ng.h/mL | Standard Deviation 16720 |
| TMC435 200 mg (Cohort 2, Panel A) | Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 231300 ng.h/mL | Standard Deviation 96890 |
Secondary
Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows mean (standard deviation) of Css,av for TMC435 in treatment-experienced HCV-infected participants (non-responders and relapsers, see defined above) at selected time points following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22.
Time frame: Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Population: All participants who received treatment were included in the pharmacokinetic (PK) analysis, however, due to various reasons (ie, missing samples at certain time points, or exclusion of specific plasma concentrations from the PK analysis) not all PK parameters could always be calculated for each participant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 820.8 ng/ml | Standard Deviation 580.1 |
| TMC435 75 mg (Cohort 1, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 2435 ng/ml | Standard Deviation 1909 |
| Placebo (Cohort 1, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 6353 ng/ml | Standard Deviation 5313 |
| TMC435 200 mg (Cohort 2, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 9613 ng/ml | Standard Deviation 3981 |
Secondary
Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
The table below shows mean (standard deviation)of Css,av for TMC435 in treatment-naïve HCV-infected participants at selected time points administered TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). See treatment-naïve defined above. The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10.
Time frame: Day 7 (predose); Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel A, Cohorts 1 and 2) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose) (Panel B, Cohorts 1 and 2)
Population: All participants who received treatment were included in the pharmacokinetic (PK) analysis, however, due to various reasons (ie, missing samples at certain time points, or exclusion of specific plasma concentrations from the PK analysis) not all PK parameters could always be calculated for each participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 7 | 180.9 ng/ml | Standard Deviation 90.04 |
| TMC435 25 mg (Cohort 1, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 170.4 ng/ml | Standard Deviation 62.42 |
| TMC435 75 mg (Cohort 1, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 7 | 832.3 ng/ml | Standard Deviation 415.1 |
| TMC435 75 mg (Cohort 1, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 681.4 ng/ml | Standard Deviation 414.7 |
| Placebo (Cohort 1, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 7 | 5714 ng/ml | Standard Deviation 4157 |
| Placebo (Cohort 1, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 7117 ng/ml | Standard Deviation 6699 |
| TMC435 200 mg (Cohort 2, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 7 | NA ng/ml | — |
| TMC435 200 mg (Cohort 2, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 186.5 ng/ml | Standard Deviation 115.7 |
| Placebo (Cohort 2, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 7 | NA ng/ml | — |
| Placebo (Cohort 2, Panel A) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 986.0 ng/ml | Standard Deviation 1087 |
| TMC435 200 mg (Cohort 2, Panel B) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 7 | NA ng/ml | — |
| TMC435 200 mg (Cohort 2, Panel B) | Average Steady-state Plasma Concentration (Css,av) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 7182 ng/ml | Standard Deviation 5415 |
Secondary
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (Week 1) following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-experienced participants considered non-responders (defined as participants who achieved less than a 2 log10 IU/mL decline from baseline in plasma HCV RNA levels after 12 weeks of previous interferon \[IFN\]-based therapy \[pegylated or non-pegylated\]) or relapsers (defined as a participant with undetectable plasma HCV RNA at the end of treatment of previous IFN-based therapy and subsequent confirmed detectable plasma HCV RNA levels during follow-up).
Time frame: Day 7
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -3.80 log10 IU/mL | Standard Error 0.432 |
| TMC435 75 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -4.68 log10 IU/mL | Standard Error 0.224 |
| Placebo (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -4.49 log10 IU/mL | Standard Error 0.318 |
| TMC435 200 mg (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -0.50 log10 IU/mL | Standard Error 0.152 |
| Placebo (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Experienced HCV-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | -4.08 log10 IU/mL | Standard Error 0.387 |
Secondary
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (at Week 1) following treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 in treatment-naïve HCV-infected participants. (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Time frame: Day 7
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | -2.63 log10 IU/mL | Standard Error 0.377 |
| TMC435 75 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | -3.48 log10 IU/mL | Standard Error 0.285 |
| Placebo (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | -0.08 log10 IU/mL | Standard Error 0.101 |
| TMC435 200 mg (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | -4.18 log10 IU/mL | Standard Error 0.158 |
| Placebo (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel A) | 0.30 log10 IU/mL | Standard Error 0.08 |
Secondary
Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the change from Baseline in plasma levels of HCV RNA on Day 7 (at Week 1) following treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 in treatment-naïve HCV-infected participants (A treatment-naive participant is someone who has never taken drugs for their HCV infection).
Time frame: Day 7
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -3.47 log10 IU/mL | Standard Error 0.5 |
| TMC435 75 mg (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -4.55 log10 IU/mL | Standard Error 0.192 |
| Placebo (Cohort 1, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -1.73 log10 IU/mL | Standard Error 0.441 |
| TMC435 200 mg (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -4.68 log10 IU/mL | Standard Error 0.135 |
| Placebo (Cohort 2, Panel A) | Change From Baseline in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (log10 IU/mL) on Day 7 in Treatment-Naïve HCV-Infected Participants (Cohort 1 and 2, Panel B) | -1.64 log10 IU/mL | Standard Error 0.793 |
Secondary
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with an initial suboptimal response defined as less than 2 log10 change of plasma in plasma level of HCV ribonucleic acid (RNA) at Day 2 or 3 (depending when visit was scheduled) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22.
Time frame: Day 2 or 3
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 1 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 0 Participants |
| Placebo (Cohort 1, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 0 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 8 Participants |
| Placebo (Cohort 2, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | 1 Participants |
Secondary
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the number of treatment-naïve participants with an initial suboptimal response defined as less than 2 log10 change in plasma level of hepatitis C virus (HCV) ribonucleic acid (RNA) on Day 2 or 3 (depending when visit was scheduled) following treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22. See treatment-naive defined above.
Time frame: Day 2 or 3
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | 3 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | 1 Participants |
| Placebo (Cohort 1, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | 6 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | 0 Participants |
| Placebo (Cohort 2, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | 3 Participants |
Secondary
Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the number of treatment-naïve participants with an initial suboptimal response defined as less than 2 log10 change in plasma plasma level of hepatitis C virus (HCV) ribonucleic acid (RNA) on Day 2 or 3 (depending when visit was scheduled) after treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. See treatment-naive defined above.
Time frame: Day 2 or 3
Population: The intent-to-treat (ITT) population, defined as all participants who were randomized and received at least one dose of study medication (TMC435) was used for all analyses.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | 2 Participants | 0.646 |
| TMC435 75 mg (Cohort 1, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | 0 Participants | 0.489 |
| Placebo (Cohort 1, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | 5 Participants | 0.64 |
| TMC435 200 mg (Cohort 2, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | 0 Participants | 0.584 |
| Placebo (Cohort 2, Panel A) | Initial Suboptimal Responses Following Treatment With TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | 1 Participants | 0.156 |
Secondary
Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the mean (standard deviation) Cmax for treatment-experienced participants (non-responders and relapsers, see defined above) following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 28 in the 4 treatment groups listed below from left to right were 8, 8, 10, and 3.
Time frame: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Population: All participants who received treatment were included in the pharmacokinetic (PK) analysis, however, due to various reasons (ie, missing samples at certain time points, or exclusion of specific plasma concentrations from the PK analysis) not all PK parameters could always be calculated for each participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 1 | 882.1 ng/mL | Standard Deviation 273.2 |
| TMC435 25 mg (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 1481 ng/mL | Standard Deviation 879.6 |
| TMC435 75 mg (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 4383 ng/mL | Standard Deviation 2374 |
| TMC435 75 mg (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 1 | 2422 ng/mL | Standard Deviation 919 |
| Placebo (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 1 | 2877 ng/mL | Standard Deviation 1399 |
| Placebo (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 8452 ng/mL | Standard Deviation 6112 |
| TMC435 200 mg (Cohort 2, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 1 | 3870 ng/mL | Standard Deviation 565 |
| TMC435 200 mg (Cohort 2, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 12220 ng/mL | Standard Deviation 2917 |
Secondary
Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
The table below shows the mean (standard deviation) Cmax for treatment-naïve participants at selected time points who were treated with TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) and with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B). See treatment-naïve defined above. The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 8, 7, 9, 9, and 10.
Time frame: Days 1 and 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Population: All participants who received treatment were included in the pharmacokinetic (PK) analysis, however, due to various reasons (ie, missing samples at certain time points, or exclusion of specific plasma concentrations from the PK analysis) not all PK parameters could always be calculated for each participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 251.1 ng/mL | Standard Deviation 77.4 |
| TMC435 25 mg (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 307.1 ng/mL | Standard Deviation 88.16 |
| TMC435 75 mg (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 1008 ng/mL | Standard Deviation 490.9 |
| TMC435 75 mg (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 1058 ng/mL | Standard Deviation 547.5 |
| Placebo (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 3369 ng/mL | Standard Deviation 1760 |
| Placebo (Cohort 1, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 11180 ng/mL | Standard Deviation 8522 |
| TMC435 200 mg (Cohort 2, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 239.6 ng/mL | Standard Deviation 125.8 |
| TMC435 200 mg (Cohort 2, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 329.4 ng/mL | Standard Deviation 186.9 |
| Placebo (Cohort 2, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 958.0 ng/mL | Standard Deviation 448.9 |
| Placebo (Cohort 2, Panel A) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 1609 ng/mL | Standard Deviation 1310 |
| TMC435 200 mg (Cohort 2, Panel B) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 1 | 3945 ng/mL | Standard Deviation 2096 |
| TMC435 200 mg (Cohort 2, Panel B) | Maximum Plasma Concentration (Cmax) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 10900 ng/mL | Standard Deviation 6974 |
Secondary
Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows mean (standard deviation) of C0h for treatment-experienced participants (non-responders and relapsers, see defined above) following treatment with TMC435 coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22. The number of participants analyzed at Day 2 and Day 28 differed as follows: At Day 2, the number of participants in the 4 treatment groups (from left to right) were 8, 7, 10, and 5; the number of participants analyzed at Day 28 in the 4 treatment groups (from left to right) were 9, 8, 10, and 4.
Time frame: Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Population: All participants who received treatment were included in the pharmacokinetic (PK) analysis, however, due to various reasons (ie, missing samples at certain time points, or exclusion of specific plasma concentrations from the PK analysis) not all PK parameters could always be calculated for each participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2 | 278.4 ng/mL | Standard Deviation 192.2 |
| TMC435 25 mg (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 324.3 ng/mL | Standard Deviation 351.9 |
| TMC435 75 mg (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 1431 ng/mL | Standard Deviation 1501 |
| TMC435 75 mg (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2 | 733.6 ng/mL | Standard Deviation 436.4 |
| Placebo (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2 | 669.8 ng/mL | Standard Deviation 301.7 |
| Placebo (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 4145 ng/mL | Standard Deviation 4425 |
| TMC435 200 mg (Cohort 2, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2 | 1280 ng/mL | Standard Deviation 955.8 |
| TMC435 200 mg (Cohort 2, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28 | 5593 ng/mL | Standard Deviation 3817 |
Secondary
Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B)
The table below shows mean (standard deviation) of C0h of TMC435 at selected time points following treatment with TMC435 for 7 days followed by TMC435 coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 (Panel A) or with TMC435 coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B) in treatment-naïve participants (see treatment-naïve defined above).The number of participants analyzed at Day 28 in the 6 treatment groups listed below from left to right were 9, 9, 8, 9, 9, and 10.
Time frame: Day 2 (predose) and Day 28 (predose and 0.5, 1, 2, 4, 6, 8, and 10 hours postdose)
Population: All participants who received treatment were included in the pharmacokinetic (PK) analysis, however, due to various reasons (ie, missing samples at certain time points, or exclusion of specific plasma concentrations from the PK analysis) not all PK parameters could always be calculated for each participant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 2 | 64.51 ng/ml | Standard Deviation 37.57 |
| TMC435 25 mg (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 64.78 ng/ml | Standard Deviation 35.15 |
| TMC435 75 mg (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 331.6 ng/ml | Standard Deviation 326.6 |
| TMC435 75 mg (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 2 | 209.3 ng/ml | Standard Deviation 107.4 |
| Placebo (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 6913 ng/ml | Standard Deviation 7726 |
| Placebo (Cohort 1, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 2 | 1053 ng/ml | Standard Deviation 526.5 |
| TMC435 200 mg (Cohort 2, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 2 | 65.73 ng/ml | Standard Deviation 41.75 |
| TMC435 200 mg (Cohort 2, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 95.83 ng/ml | Standard Deviation 61.56 |
| Placebo (Cohort 2, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 2 | 281.6 ng/ml | Standard Deviation 288.1 |
| Placebo (Cohort 2, Panel A) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 632.8 ng/ml | Standard Deviation 1128 |
| TMC435 200 mg (Cohort 2, Panel B) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 28 | 4818 ng/ml | Standard Deviation 5071 |
| TMC435 200 mg (Cohort 2, Panel B) | Predose Plasma Concentration (C0h) of TMC435 in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B) | Day 2 | 821.7 ng/ml | Standard Deviation 422.9 |
Secondary
Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) in each treatment group in Cohort 4, Panel C and in Cohort 5, Panel D with an SVR to treatment defined as having an undetectable plasma level of HCV ribonucleic acid after the last planned dose of the entire treatment regimen. SVR was measured at 4, 8, 12, and 24 weeks after the last dose of treatment (SVR4, SVR8, SVR12, and SVR24, respectively).
Time frame: SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72)
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR4 | 2 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR8 | 1 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR12 | 1 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR24 | 1 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR4 | 3 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR24 | 3 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR8 | 3 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR12 | 3 Participants |
| Placebo (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR24 | 5 Participants |
| Placebo (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR8 | 4 Participants |
| Placebo (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR12 | 5 Participants |
| Placebo (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR4 | 4 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR4 | 1 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR8 | 0 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR24 | 0 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR12 | 0 Participants |
| Placebo (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR24 | 3 Participants |
| Placebo (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR12 | 3 Participants |
| Placebo (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR8 | 3 Participants |
| Placebo (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | SVR4 | 3 Participants |
Secondary
Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
The table below shows the number of treatment-naïve participants with an SVR to treatment (defined as having an undetectable plasma level of HCV ribonucleic acid after the last planned dose of treatment) for the treatment groups in Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined). SVR was measured at 4, 8, 12, and 24 weeks after the last dose of treatment (SVR4, SVR8, SVR12, and SVR24, respectively). See treatment-naïve defined above.
Time frame: SVR4 (Week 52), SVR8 (Week 56), SVR12 (Week 60), and SVR24 (Week 72)
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR4 | 12 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR8 | 12 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR12 | 12 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR24 | 10 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR4 | 16 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR24 | 15 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR8 | 14 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR12 | 15 Participants |
| Placebo (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR24 | 9 Participants |
| Placebo (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR8 | 9 Participants |
| Placebo (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR12 | 9 Participants |
| Placebo (Cohort 1, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR4 | 11 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR4 | 12 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR8 | 12 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR24 | 12 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR12 | 12 Participants |
| Placebo (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR24 | 5 Participants |
| Placebo (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR12 | 5 Participants |
| Placebo (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR8 | 5 Participants |
| Placebo (Cohort 2, Panel A) | Sustained Virologic Response (SVR) in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | SVR4 | 5 Participants |
Secondary
Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (less than 25 IU/mL undetectable) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22.
Time frame: 4 Weeks (Wks), 44 Wks, and 48 Wks
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Entire treatment period (48 Wks) | 3 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During treatment with RBV and PegIFNα-2a (44 Wks) | 1 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During TMC435/Placebo treatment (4 Wks) | 2 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During TMC435/Placebo treatment (4 Wks) | 1 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Entire treatment period (48 Wks) | 4 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During treatment with RBV and PegIFNα-2a (44 Wks) | 3 Participants |
| Placebo (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During TMC435/Placebo treatment (4 Wks) | 0 Participants |
| Placebo (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Entire treatment period (48 Wks) | 4 Participants |
| Placebo (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During treatment with RBV and PegIFNα-2a (44 Wks) | 4 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Entire treatment period (48 Wks) | 1 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During treatment with RBV and PegIFNα-2a (44 Wks) | 0 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During TMC435/Placebo treatment (4 Wks) | 1 Participants |
| Placebo (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During TMC435/Placebo treatment (4 Wks) | 0 Participants |
| Placebo (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Entire treatment period (48 Wks) | 1 Participants |
| Placebo (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | During treatment with RBV and PegIFNα-2a (44 Wks) | 1 Participants |
Secondary
Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B)
The table below shows the number of treatment-naïve participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma HCV ribonucleic acid (RNA) level from the lowest level reached, or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (less than 25 IU/mL undetectable) after treatment with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on days 8, 15, and 22 (Panel A) and after treatment with TMC435 or placebo coadministered with ribavirin for 28 days + PegIFNα-2a on Days 1, 8, 15, and 22 (Panel B).
Time frame: 4 Weeks (Wks), 44 Wks, and 48 Wks
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses. Note: Number of participants analyzed during the PegIFNα-2a and ribavirin treatment period of up to 44 weeks is N=16 for TMC435 25 mg, N=17 for TMC435 75 mg, and N=17 for TMC435 200 mg.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During TMC435/Placebo treatment (4 Wks) | 2 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | Entire treatment period (48 Wks) | 3 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During treatment with RBV and PegIFNα-2a (44 Wks) | 1 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During TMC435/Placebo treatment (4 Wks) | 2 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | Entire treatment period (48 Wks) | 3 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During treatment with RBV and PegIFNα-2a (44 Wks) | 1 Participants |
| Placebo (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During TMC435/Placebo treatment (4 Wks) | 0 Participants |
| Placebo (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | Entire treatment period (48 Wks) | 0 Participants |
| Placebo (Cohort 1, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During treatment with RBV and PegIFNα-2a (44 Wks) | 0 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | Entire treatment period (48 Wks) | 4 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During treatment with RBV and PegIFNα-2a (44 Wks) | 3 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During TMC435/Placebo treatment (4 Wks) | 1 Participants |
| Placebo (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During TMC435/Placebo treatment (4 Wks) | 0 Participants |
| Placebo (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | Entire treatment period (48 Wks) | 0 Participants |
| Placebo (Cohort 2, Panel A) | Viral Breakthrough in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1, Panel A and B) | During treatment with RBV and PegIFNα-2a (44 Wks) | 0 Participants |
Secondary
Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants combined (non-responders and relapsers, see defined above) with viral relapse, defined as having confirmed detectable plasma level of HCV ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment who received TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22.
Time frame: Up to Week 72
Population: The analysis population used to evaluate viral relapse included participants in the intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) who were treatment-experienced and had undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Relapse | 3 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | No relapse | 3 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Relapse | 0 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | No relapse | 3 Participants |
| Placebo (Cohort 1, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Relapse | 1 Participants |
| Placebo (Cohort 1, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | No relapse | 5 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | No relapse | 0 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Relapse | 3 Participants |
| Placebo (Cohort 2, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Relapse | 0 Participants |
| Placebo (Cohort 2, Panel A) | Viral Relapse in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | No relapse | 3 Participants |
Secondary
Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
The table below shows the number of treatment-naïve participants with viral relapse (defined as having confirmed detectable plasma level of HCV ribonucleic acid \[RNA\] during the follow-up period in participants with undetectable plasma HCV RNA \[less than 25 IU/mL undetectable\] at the end of treatment) for the treatment groups in Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined). See treatment-naïve defined above.
Time frame: Up to Week 72
Population: The analysis population used to evaluate viral relapse included participants in the intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) who were treatment-naïve and had undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Relapse | 2 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Missing follow-up | 1 Participants |
| TMC435 25 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | No relapse | 12 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | No relapse | 17 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Relapse | 1 Participants |
| TMC435 75 mg (Cohort 1, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Missing follow-up | 0 Participants |
| Placebo (Cohort 1, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | No relapse | 10 Participants |
| Placebo (Cohort 1, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Relapse | 2 Participants |
| Placebo (Cohort 1, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Missing follow-up | 0 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Relapse | 1 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Missing follow-up | 0 Participants |
| TMC435 200 mg (Cohort 2, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | No relapse | 13 Participants |
| Placebo (Cohort 2, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | No relapse | 5 Participants |
| Placebo (Cohort 2, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Relapse | 0 Participants |
| Placebo (Cohort 2, Panel A) | Viral Relapse in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Missing follow-up | 0 Participants |
Secondary
Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) treated with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22 who met the following virologic response parameters: rapid virological response (RVR) defined as having undetectable plasma HCV ribonucleic acid (RNA) at Week 4; early virologic response (EVR) defined as change from baseline in plasma HCV RNA of greater than or equal to 2 log 10 at Week 12; a complete EVR (cEVR) defined as a EVR having undetectable plasma HCV RNA at Week 12; an extended RVR (eRVR) defined as undetectable plasma HCV RNA at Week 4 and 12; and a partial response defined as EVR but not reaching undetectability while on treatment.
Time frame: Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR)
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | eRVR | 2 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | RVR | 2 Participants | 0.646 |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Partial response | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | EVR | 6 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | cEVR | 4 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | eRVR | 4 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | cEVR | 4 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | EVR | 7 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Partial response | 1 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | RVR | 5 Participants | 0.489 |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | cEVR | 5 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | RVR | 3 Participants | 0.64 |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | EVR | 8 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | eRVR | 3 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Partial response | 1 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Partial response | 5 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | RVR | 0 Participants | 0.584 |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | eRVR | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | cEVR | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | EVR | 8 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | cEVR | 3 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | eRVR | 3 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | RVR | 3 Participants | 0.156 |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Partial response | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | EVR | 4 Participants | — |
Secondary
Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined)
The table below shows the number of treatment-naïve participants in the treatment groups for Cohort 1 (Panel A and B combined) and in Cohort 2 (Panel A and B combined) who met the following virologic response parameters: rapid virological response (RVR) defined as having undetectable plasma HCV ribonucleic acid (RNA) at Week 4; early virologic response (EVR) defined as change from baseline in plasma HCV RNA of greater than or equal to 2 log 10 at Week 12); a complete EVR (cEVR) defined as a complete EVR having undetectable plasma HCV RNA at Week 12); an extended RVR (eRVR) defined as undetectable plasma HCV RNA at Week 4 and 12; and a partial response defined as EVR but not reaching undetectability while on treatment.
Time frame: Week 4 (RVR), Week 12 (EVR, cEVR, and partial response), and Week 4 and 12 (eRVR)
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | eRVR | 8 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | RVR | 8 Participants | 0.646 |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Partial response | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | EVR | 16 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | cEVR | 13 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | eRVR | 13 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | cEVR | 17 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | EVR | 19 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Partial response | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | RVR | 13 Participants | 0.489 |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | cEVR | 7 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | RVR | 3 Participants | 0.64 |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | EVR | 12 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | eRVR | 3 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Partial response | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Partial response | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | RVR | 13 Participants | 0.584 |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | eRVR | 13 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | cEVR | 16 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | EVR | 16 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | cEVR | 5 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | eRVR | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | RVR | 0 Participants | 0.156 |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | Partial response | 1 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Response Parameters in Treatment-Naïve Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A and B Combined) | EVR | 6 Participants | — |
Secondary
Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D)
The table below shows the number of treatment-experienced participants (non-responders and relapsers, see defined above) with the following virologic responses to treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 1, 8, 15, and 22: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than \[\<\] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, \<25 IU/mL undetectable); plasma levels of HCV RNA \<100 IU/mL; and plasma levels of HCV RNA \<1000 at the time points listed. Note: in the table below, the number of participants (n) analyzed in the TMC435 200 mg (Cohort 4, Panel B) on Day 28 (Week 4) was n=4.
Time frame: Day 2 or 3, Day 7, and Day 28
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <100 IU/mL | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL undetectable | 2 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: > or = 2 log10 change from baseline | 8 Participants | 0.646 |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <1000 IU/mL | 5 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: > or = 2 log10 change from baseline | 8 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <1000 IU/mL | 3 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <1000 IU/mL | 6 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <100 IU/mL | 6 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL detectable or undetectable | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: > or = 2 log10 change from baseline | 8 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <100 IU/mL | 2 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL detectable or undetectable | 4 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL detectable or undetectable | 7 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: > or = 2 log10 change from baseline | 9 Participants | 0.489 |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL undetectable | 5 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <100 IU/mL | 4 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <100 IU/mL | 8 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <1000 IU/mL | 7 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: > or = 2 log10 change from baseline | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <100 IU/mL | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: > or = 2 log10 change from baseline | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <1000 IU/mL | 8 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <1000 IU/mL | 3 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL detectable or undetectable | 2 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: > or = 2 log10 change from baseline | 10 Participants | 0.64 |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: > or = 2 log10 change from baseline | 10 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: > or = 2 log10 change from baseline | 10 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL detectable or undetectable | 3 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL detectable or undetectable | 7 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL undetectable | 3 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <100 IU/mL | 5 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <100 IU/mL | 7 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <1000 IU/mL | 5 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <1000 IU/mL | 8 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <1000 IU/mL | 10 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <100 IU/mL | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: > or = 2 log10 change from baseline | 2 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <100 IU/mL | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <1000 IU/mL | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL detectable or undetectable | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: > or = 2 log10 change from baseline | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <1000 IU/mL | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: > or = 2 log10 change from baseline | 1 Participants | 0.584 |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <100 IU/mL | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <1000 IU/mL | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL undetectable | 3 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <1000 IU/mL | 3 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: > or = 2 log10 change from baseline | 4 Participants | 0.156 |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <100 IU/mL | 4 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: > or = 2 log10 change from baseline | 4 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <1000 IU/mL | 4 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: > or = 2 log10 change from baseline | 5 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Experienced Hepatitis C Virus (HCV)-Infected Participants (Cohort 4, Panel C and Cohort 5, Panel D) | Day 28: <25 IU/mL detectable or undetectable | 4 Participants | — |
Secondary
Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A)
The table below shows the number of treatment-naïve HCV-infected participants treated with TMC435 or placebo for 7 days followed by TMC435 or placebo coadministered with ribavirin for 21 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22 who had the following virologic responses: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than \[\<\] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, \<25 IU/mL undetectable); plasma levels of HCV RNA \<100 IU/mL; and plasma levels of HCV RNA \<1000 at the time points listed. See treatment-naive defined above.
Time frame: Day 2 or 3, Day 7, and Day 28
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <100 IU/mL | 1 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL undetectable | 5 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: > or = 2 log10 change from baseline | 6 Participants | 0.646 |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <1000 IU/mL | 3 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: > or = 2 log10 change from baseline | 7 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <1000 IU/mL | 2 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL detectable or undetectable | 1 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <1000 IU/mL | 7 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <100 IU/mL | 6 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL detectable or undetectable | 1 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: > or = 2 log10 change from baseline | 7 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <100 IU/mL | 1 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL detectable or undetectable | 5 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL detectable or undetectable | 8 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: > or = 2 log10 change from baseline | 9 Participants | 0.489 |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL undetectable | 5 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL detectable or undetectable | 1 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <100 IU/mL | 3 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <100 IU/mL | 8 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <1000 IU/mL | 6 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: > or = 2 log10 change from baseline | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <100 IU/mL | 1 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: > or = 2 log10 change from baseline | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <1000 IU/mL | 8 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <1000 IU/mL | 5 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: > or = 2 log10 change from baseline | 0 Participants | 0.64 |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: > or = 2 log10 change from baseline | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: > or = 2 log10 change from baseline | 4 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL detectable or undetectable | 1 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL undetectable | 1 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <100 IU/mL | 1 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <1000 IU/mL | 2 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <100 IU/mL | 4 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: > or = 2 log10 change from baseline | 8 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <100 IU/mL | 1 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <1000 IU/mL | 6 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL detectable or undetectable | 1 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL detectable or undetectable | 1 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: > or = 2 log10 change from baseline | 9 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <1000 IU/mL | 7 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: > or = 2 log10 change from baseline | 9 Participants | 0.584 |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <100 IU/mL | 7 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <1000 IU/mL | 7 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL undetectable | 7 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL detectable or undetectable | 7 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: > or = 2 log10 change from baseline | 0 Participants | 0.156 |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: > or = 2 log10 change from baseline | 1 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: > or = 2 log10 change from baseline | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel A) | Day 28: <25 IU/mL detectable or undetectable | 0 Participants | — |
Secondary
Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B)
The table below shows the number of treatment-naive HCV-Infected participants with the following virologic responses to treatment with TMC435 or placebo coadministered with ribavirin for 28 days + peginterferon alpha-2a (PegIFNα-2a) on Days 8, 15, and 22: plasma levels of HCV ribonucleic acid (RNA) of greater than or equal to 2 log10 decline from Baseline; plasma levels of HCV RNA below the limit of quantification (ie, less than \[\<\] 25 IU/mL detectable or undetectable); plasma levels of HCV RNA below the limit of detection (ie, \<25 IU/mL undetectable); plasma levels of HCV RNA \<100 IU/mL; and plasma levels of HCV RNA \<1000 at the time points listed. See treatment-naive defined above.
Time frame: Day 2 or 3, Day 7, and Day 28
Population: The intent-to-treat population (defined as all participants who were randomized and received at least one dose of study medication) was used for all analyses.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <100 IU/mL | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL undetectable | 3 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: > or = 2 log10 change from baseline | 7 Participants | 0.646 |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <1000 IU/mL | 5 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: > or = 2 log10 change from baseline | 8 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <1000 IU/mL | 4 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <1000 IU/mL | 7 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <100 IU/mL | 6 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL detectable or undetectable | 1 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: > or = 2 log10 change from baseline | 7 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <100 IU/mL | 1 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL detectable or undetectable | 6 Participants | — |
| TMC435 25 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL detectable or undetectable | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: > or = 2 log10 change from baseline | 9 Participants | 0.489 |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL undetectable | 8 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <100 IU/mL | 6 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <100 IU/mL | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <1000 IU/mL | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: > or = 2 log10 change from baseline | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <100 IU/mL | 1 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: > or = 2 log10 change from baseline | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <1000 IU/mL | 9 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <1000 IU/mL | 5 Participants | — |
| TMC435 75 mg (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL detectable or undetectable | 1 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: > or = 2 log10 change from baseline | 2 Participants | 0.64 |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: > or = 2 log10 change from baseline | 2 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: > or = 2 log10 change from baseline | 6 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL detectable or undetectable | 3 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL undetectable | 2 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <100 IU/mL | 3 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 1, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <1000 IU/mL | 4 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <100 IU/mL | 5 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: > or = 2 log10 change from baseline | 9 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <100 IU/mL | 1 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <1000 IU/mL | 6 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL detectable or undetectable | 3 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: > or = 2 log10 change from baseline | 9 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <1000 IU/mL | 9 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL undetectable | 1 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: > or = 2 log10 change from baseline | 9 Participants | 0.584 |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <100 IU/mL | 9 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <1000 IU/mL | 9 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL undetectable | 6 Participants | — |
| TMC435 200 mg (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL detectable or undetectable | 9 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: > or = 2 log10 change from baseline | 2 Participants | 0.156 |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <100 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL detectable or undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <100 IU/mL | 1 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: > or = 2 log10 change from baseline | 2 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <1000 IU/mL | 2 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <1000 IU/mL | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: > or = 2 log10 change from baseline | 1 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 7: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 2/3: <25 IU/mL undetectable | 0 Participants | — |
| Placebo (Cohort 2, Panel A) | Virologic Responses Following Treatment With TMC435 in Treatment-Naive Hepatitis C Virus (HCV)-Infected Participants (Cohort 1 and 2, Panel B) | Day 28: <25 IU/mL detectable or undetectable | 1 Participants | — |