Hepatitis C
Conditions
Keywords
Hepatitis C, TMC435, HCV, Hep C, Genotype 1
Brief summary
The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients will also receive peginterferon alfa-2a and ribavirin as part of their treatment.
Detailed description
This is a randomized, double-blind (neither physician nor patients knows the name of the assigned drug), placebo-controlled study of TMC435 in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients in this study will also receive two other drugs for their infection called peginterferon alfa-2a and ribavirin. The purpose of the study is to investigate if TMC435 is superior to placebo in reducing hepatitis C virus to an undetectable level 24 weeks after the end of treatment. For the first 12 weeks, patients will take TMC435 or placebo, plus peginterferon alfa-2a and ribavirin. For the next 12 weeks, patients will take peginterferon alfa-2a and ribavirin only. After that, some patients will continue to take peginterferon alfa-2a and ribavirin for up to 24 additional weeks. Other patients will stop taking peginterferon alfa-2a and ribavirin. The study doctor will inform each patient about how to take their study medication and when they should stop taking it. After a patient stops taking study medication, they will continue to come to the doctor's office for study visits until a total of 72 weeks after they enroll in the study. The total duration of the study is 78 weeks (including screening). Patients will be monitored for safety throughout the study. Study assessments at each study visit may include but are not limited to: blood and urine collection for testing, ECG assessments (a measurement of the electrical activity of your heart), patient questionnaires, and physical examinations TMC435 will be taken as an oral capsule of 150 mg once per day. Peginterferon (Pegasys ®) will be given as an injection of 180 µg once each week. Ribavirin (Copegus ®) will be taken as a tablet twice each day and the dose will depend on your body weight.
Interventions
DRUGTMC435
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks
DRUGPlacebo
150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 48 weeks
One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFN alpha-2a once weekly for up to 48 weeks.
DRUGRibavirin (RBV)
200-mg tablets of RBV (body-weight adjusted dose) taken orally (by mouth) twice daily for up to 48 weeks.
Sponsors
Janssen R&D Ireland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Genotype 1 hepatitis C infection (confirmed at screening) * Have previously received peginterferon-based therapy for at least 24 weeks with documented HCV RNA at last measurement and relapsed within 1 year of last taking medication * Liver biopsy within 3 years before screening (or between the screening and baseline visit) showing chronic hepatitis C infection * Must agree to use 2 forms of effective contraception throughout study (both males and females)
Exclusion criteria
* Infection with HIV or non-genotype 1 hepatitis C * Liver disease not related to hepatitic C infection * Hepatic decompensation * Significant laboratory abnormalities or other active diseases * Pregnant or planning to become pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) | Week 36 or Week 60 | The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) | Week 72 | The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72. |
| The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) | Week 48 or Week 72 | The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 24 weeks after planned end of treatment. |
| The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4) | Week 28 or Week 52 | The table below shows the percentage of participants in each treatment group who achieved a SVR4, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 4 weeks after planned end of treatment. |
| Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48 | The table below shows change from baseline in log10 HCV RNA levels. |
| Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48 | The table below shows actual values of log10 HCV RNA levels. From Week 4 onwards, most participants in TMC 435 150mg 12Wks PR24/48 group had plasma HCV RNA levels below the limit of detection of the HCV RNA assay. |
| The Percentage of Participants With On-treatment Virologic Response at All Time Points | Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42 | The table below shows the percentage of participants with HCV ribonucleic acid (RNA plasma levels below the limit of detection (ie, \<25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than \[\<\] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA \<100 IU/mL, the percentage of participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA. |
| The Percentage of Participants Achieving a Rapid Virologic Response (RVR) | Week 4 | The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment. |
| The Percentage of Participants Achieving a Early Virologic Response (EVR) | Week 12 | The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of greater than or equal to 2 log10 at Week 12. |
| The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR) | Week 4 and Week 12 | The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12. |
| The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4 | Week 4 | The table below shows the percentage of participants in each treatment group with \<1 log10 HCV RNA decrease at Week 4. |
| Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4 | Week 4 | The table below shows the percentage of participants in each treatment group with HCV RNA levels \>1000 IU/mL at Week 4. |
| The Percentage of Participants With Null Response | Week 12 | The table below shows the percentage of participants with null response, defined as \<2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline. |
| The Percentage of Participants With Partial Response | Week 12 | The table below shows the percentage of participants with partial response, defined as =\>2 log10 reduction in Hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment. |
| The Percentage of Participants With Viral Breakthrough | Up to Week 48 | The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), 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 (\<25 IU/mL undetectable). |
| The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) | Week 12 | The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12. |
| The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule | Week 24 | The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] levels \<25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks. |
| The Percentage of Participants With On-treatment Failure | Week 48 | The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment. |
| Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable | Up to Week 48 | The table below shows mean time in days to reach HCV RNA levels \<25 IU/mL undetectable or detectable. |
| Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable | Up to Week 48 | The table below shows mean time in days to reach HCV RNA levels \<25 IU/mL undetectable or detectable. |
| Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL | Up to Week 48 | The table below shows mean time in days to reach HCV RNA levels \<100 IU/mL. |
| Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL | Up to Week 48 | The table below shows mean time in days to reach HCV RNA levels \<1000 IU/mL. |
| The Percentage of Participants With Viral Breakthrough at Different Time Points | Up to Week 48 | The table below shows the percentage of participants at different time points 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 (ie, lowest value measured in between baseline and current value), 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 (\<25 IU/mL undetectable). |
| Time From End-of-treatment to Viral Relapse | Up to Week 72 | The table below shows the mean number of days to viral relapse, defined as participants having confirmed detectable plasma level of Hepatitis C Virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (\<25 IU/mL undetectable) at the end of treatment. |
| The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) | Up to Week 48 | The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 156 of 260 participants in the TMC435 treatment group and 84 of 133 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range. |
| Median Time to Normalization of Alanine Aminotransferase (ALT) Levels | Up to Week 48 | The table below shows the median time to normalization of ALT levels. |
| Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) | From the time of administration up to 24 hours after dosing through Week 12 | The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours (AUC 24hr) after dosing for TMC435. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then the median of AUC value across visits for each participant was used to calculate the mean AUC 24 hr for the study. |
| Plasma Concentration of TMC435: Predose Plasma Concentration (C0h) | Before administration of TMC435 through Week 12 | The table below shows mean (standard deviation) of C0h values of TMC435. To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then the median of C0h values across visits for each participant was used to calculate the mean C0h for the study. |
| Plasma Concentration of TMC435: Systemic Clearance (CL) | From the time of administration through Week 12 | The table below shows mean (standard deviation) of CL values of TMC435. To calculate the mean CL for the study, CL values were derived for each participant at each visit and then the median of CL values across visits for each participant was used to calculate the mean CL for the study. |
| The Percentage of Participants With Viral Relapse | Up to Week 72 | The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (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. |
Countries
Australia, Austria, Belgium, Canada, France, Germany, New Zealand, Poland, Puerto Rico, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted from 18 January 2011 to 4 February 2013. The study was conducted at 81 sites in 14 countries.
Pre-assignment details
394 participants were randomly allocated to the 2 treatment arms. 393 participants received at least 1 dose of study medication and were included in the intent-to-treat analysis set.
Participants by arm
| Arm | Count |
|---|---|
| TMC435 150mg 12Wks PR24/48 Participants were given TMC435 150 mg once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 24 (PR24). Treatment was to be stopped at Week 24 for participants who achieved HCV RNA \< 25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA at Week 12. Other participants continued PR until Week 48 (PR48). | 260 |
| PBO 12Wks PR48 Participants were given placebo (PBO) once daily plus peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 12 Weeks (Wks) followed by PegIFN alpha-2a (P) and RBV (R) until Week 48 (PR 48). | 133 |
| Total | 393 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 6 | 3 |
| Overall Study | Reason not specified | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 10 |
Baseline characteristics
| Characteristic | TMC435 150mg 12Wks PR24/48 | PBO 12Wks PR48 | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 52 years | 52 years |
| Sex: Female, Male Female | 81 Participants | 54 Participants | 135 Participants |
| Sex: Female, Male Male | 179 Participants | 79 Participants | 258 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 245 / 260 | 123 / 133 |
| serious Total, serious adverse events | 14 / 260 | 11 / 133 |
Outcome results
Primary
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
The table below shows the percentage of participants in each treatment group who achieved a SVR12, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid 12 weeks after planned end of treatment.
Time frame: Week 36 or Week 60
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 150mg 12Wks PR24/48 | The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) | 79.2 Percentage of participants |
| PBO 12Wks PR48 | The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) | 36.1 Percentage of participants |
Comparison: Null hypothesis: There is no difference in proportions of SVR12 between the treatment groups.p-value: <0.00195% CI: [34.6, 53]Cochran-Mantel-Haenszel
Secondary
Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows actual values of log10 HCV RNA levels. From Week 4 onwards, most participants in TMC 435 150mg 12Wks PR24/48 group had plasma HCV RNA levels below the limit of detection of the HCV RNA assay.
Time frame: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
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 (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Day 3 | 2.884 log10 IU/mL | Standard Error 0.049 |
| TMC435 150mg 12Wks PR24/48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 1 | 1.889 log10 IU/mL | Standard Error 0.041 |
| TMC435 150mg 12Wks PR24/48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 4 | 1.128 log10 IU/mL | Standard Error 0.034 |
| TMC435 150mg 12Wks PR24/48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 12 | 1.018 log10 IU/mL | Standard Error 0.034 |
| TMC435 150mg 12Wks PR24/48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 24 | 0.956 log10 IU/mL | Standard Error 0.002 |
| TMC435 150mg 12Wks PR24/48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 48 | 0.954 log10 IU/mL | Standard Error 0 |
| PBO 12Wks PR48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 24 | 1.108 log10 IU/mL | Standard Error 0.042 |
| PBO 12Wks PR48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Day 3 | 5.445 log10 IU/mL | Standard Error 0.084 |
| PBO 12Wks PR48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 12 | 2.005 log10 IU/mL | Standard Error 0.109 |
| PBO 12Wks PR48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 1 | 5.376 log10 IU/mL | Standard Error 0.084 |
| PBO 12Wks PR48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 48 | 0.995 log10 IU/mL | Standard Error 0.013 |
| PBO 12Wks PR48 | Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 4 | 3.838 log10 IU/mL | Standard Error 0.13 |
Secondary
Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The table below shows change from baseline in log10 HCV RNA levels.
Time frame: Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48
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 (MEAN) | Dispersion |
|---|---|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Day 3 | -3.537 log10 IU/mL | Standard Error 0.042 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 1 | -4.535 log10 IU/mL | Standard Error 0.04 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 4 | -5.295 log10 IU/mL | Standard Error 0.049 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 12 | -5.404 log10 IU/mL | Standard Error 0.049 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 24 | -5.449 log10 IU/mL | Standard Error 0.036 |
| TMC435 150mg 12Wks PR24/48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 48 | -5.635 log10 IU/mL | Standard Error 0.212 |
| PBO 12Wks PR48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 24 | -5.373 log10 IU/mL | Standard Error 0.07 |
| PBO 12Wks PR48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Day 3 | -1.039 log10 IU/mL | Standard Error 0.072 |
| PBO 12Wks PR48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 12 | -4.476 log10 IU/mL | Standard Error 0.113 |
| PBO 12Wks PR48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 1 | -1.099 log10 IU/mL | Standard Error 0.073 |
| PBO 12Wks PR48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 48 | -5.473 log10 IU/mL | Standard Error 0.068 |
| PBO 12Wks PR48 | Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) | Week 4 | -2.638 log10 IU/mL | Standard Error 0.125 |
Secondary
Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
The table below shows the median time to normalization of ALT levels.
Time frame: Up to Week 48
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 (MEDIAN) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Median Time to Normalization of Alanine Aminotransferase (ALT) Levels | 7.86 Weeks |
| PBO 12Wks PR48 | Median Time to Normalization of Alanine Aminotransferase (ALT) Levels | 8.00 Weeks |
Secondary
Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
The table below shows the percentage of participants in each treatment group with HCV RNA levels \>1000 IU/mL at Week 4.
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 (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4 | 1.9 Percentage of Participants |
| PBO 12Wks PR48 | Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4 | 69.9 Percentage of Participants |
Secondary
Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours (AUC 24hr) after dosing for TMC435. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then the median of AUC value across visits for each participant was used to calculate the mean AUC 24 hr for the study.
Time frame: From the time of administration up to 24 hours after dosing through Week 12
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 150mg 12Wks PR24/48 | Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) | 60987 ng*h/mL | Standard Deviation 67577.4 |
Secondary
Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
The table below shows mean (standard deviation) of C0h values of TMC435. To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then the median of C0h values across visits for each participant was used to calculate the mean C0h for the study.
Time frame: Before administration of TMC435 through Week 12
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 150mg 12Wks PR24/48 | Plasma Concentration of TMC435: Predose Plasma Concentration (C0h) | 2081 ng/mL | Standard Deviation 2807.6 |
Secondary
Plasma Concentration of TMC435: Systemic Clearance (CL)
The table below shows mean (standard deviation) of CL values of TMC435. To calculate the mean CL for the study, CL values were derived for each participant at each visit and then the median of CL values across visits for each participant was used to calculate the mean CL for the study.
Time frame: From the time of administration through Week 12
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 150mg 12Wks PR24/48 | Plasma Concentration of TMC435: Systemic Clearance (CL) | 4.92 L/h | Standard Deviation 3.438 |
Secondary
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12.
Time frame: Week 12
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 150mg 12Wks PR24/48 | The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) | 98.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR) | 27.4 Percentage of Participants |
Secondary
The Percentage of Participants Achieving a Early Virologic Response (EVR)
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of greater than or equal to 2 log10 at Week 12.
Time frame: Week 12
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 150mg 12Wks PR24/48 | The Percentage of Participants Achieving a Early Virologic Response (EVR) | 98.8 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants Achieving a Early Virologic Response (EVR) | 95.2 Percentage of Participants |
Secondary
The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12.
Time frame: Week 4 and Week 12
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 150mg 12Wks PR24/48 | The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR) | 77.6 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR) | 1.6 Percentage of Participants |
Secondary
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment.
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 (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants Achieving a Rapid Virologic Response (RVR) | 77.2 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants Achieving a Rapid Virologic Response (RVR) | 3.1 Percentage of Participants |
Secondary
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72.
Time frame: 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 | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) | 76.5 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) | 33.8 Percentage of Participants |
Comparison: Null hypothesis: There is no difference in proportions of SVR72 between the treatment groups.p-value: <0.00195% CI: [34.1, 52.5]Cochran-Mantel-Haenszel
Secondary
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 24 weeks after planned end of treatment.
Time frame: Week 48 or 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 | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) | 77.3 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) | 33.8 Percentage of Participants |
Comparison: There is no difference in proportions of SVR24 between the treatment groups.p-value: <0.00195% CI: [34.9, 53.2]Cochran-Mantel-Haenszel
Secondary
The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
The table below shows the percentage of participants in each treatment group who achieved a SVR4, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels 4 weeks after planned end of treatment.
Time frame: Week 28 or Week 52
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 150mg 12Wks PR24/48 | The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4) | 88.5 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4) | 48.1 Percentage of Participants |
Comparison: There is no difference in proportions of SVR24 between the treatment groups.p-value: <0.00195% CI: [32.1, 49.9]Cochran-Mantel-Haenszel
Secondary
The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] levels \<25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks.
Time frame: Week 24
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 150mg 12Wks PR24/48 | The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule | 90.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule | 0 Percentage of Participants |
Secondary
The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
The table below shows the percentage of participants in each treatment group with \<1 log10 HCV RNA decrease at Week 4.
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 (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4 | 0.8 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4 | 9.3 Percentage of Participants |
Secondary
The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 156 of 260 participants in the TMC435 treatment group and 84 of 133 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range.
Time frame: Up to Week 48
Population: Participants with baseline ALT values out of normal range were used for this analysis from intent-to treat population (defined as all participants who were randomized and received at least one dose of study medication).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) | 69.9 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) | 69.0 Percentage of Participants |
Secondary
The Percentage of Participants With Null Response
The table below shows the percentage of participants with null response, defined as \<2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline.
Time frame: Week 12
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 150mg 12Wks PR24/48 | The Percentage of Participants With Null Response | 1.2 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With Null Response | 4.8 Percentage of Participants |
Secondary
The Percentage of Participants With On-treatment Failure
The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment.
Time frame: Week 48
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 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Failure | 3.1 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Failure | 27.1 Percentage of Participants |
Secondary
The Percentage of Participants With On-treatment Virologic Response at All Time Points
The table below shows the percentage of participants with HCV ribonucleic acid (RNA plasma levels below the limit of detection (ie, \<25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than \[\<\] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA \<100 IU/mL, the percentage of participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA.
Time frame: Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42
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 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Day 3:<100 IU/mL | 9.1 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 20:<25 IU/mL | 99.6 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 1:<100 IU/mL | 62.2 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 1:<25 IU/mL undetectable/detectable | 35.9 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 2:<100 IU/mL | 92.2 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 8:<25 IU/mL undetectable | 95.7 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 8:<100 IU/mL | 98.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 2:<25 IU/mL undetectable/detectable | 82.6 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 16:<100 IU/mL | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 28:<25 IU/mL | 88.9 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 20:<100 IU/mL | 99.6 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 8:<25 IU/mL undetectable/detectable | 98.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 28:<100 IU/mL | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 2:<25 IU/mL undetectable | 28.3 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 36:<100 IU/mL | 90.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 16:<25 IU/mL undetectable/detectable | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 42:<100 IU/mL | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 36:<25 IU/mL | 90.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Day 3:> or = 2 log10 change from baseline | 97.6 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 20:<25 IU/mL undetectable/detectable | 99.6 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 1:> or = 2 log10 change from baseline | 99.6 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 16:<25 IU/mL | 98.4 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 2:> or = 2 log10 change from baseline | 99.6 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 28:<25 IU/mL undetectable/detectable | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 8:> or = 2 log10 change from baseline | 98.4 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 42:<25 IU/mL | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 16:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 36:<25 IU/mL undetectable/detectable | 90.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 20:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 1:<25 IU/mL undetectable | 3.9 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 28:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 42:<25 IU/mL undetectable/detectable | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 36:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Day 3:<25 IU/mL undetectable/detectable | 3.1 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 42:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Day 3:<25 IU/mL undetectable | 0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 42:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Day 3:<25 IU/mL undetectable | 0.8 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 1:<25 IU/mL undetectable | 0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 2:<25 IU/mL undetectable | 0.8 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 8:<25 IU/mL undetectable | 15.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 16:<25 IU/mL | 47.4 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 20:<25 IU/mL | 65.5 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 28:<25 IU/mL | 84.5 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 36:<25 IU/mL | 91.9 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 42:<25 IU/mL | 91.7 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Day 3:<25 IU/mL undetectable/detectable | 0.8 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 1:<25 IU/mL undetectable/detectable | 0.8 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 2:<25 IU/mL undetectable/detectable | 1.5 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 8:<25 IU/mL undetectable/detectable | 27.6 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 16:<25 IU/mL undetectable/detectable | 77.6 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 20:<25 IU/mL undetectable/detectable | 89.4 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 28:<25 IU/mL undetectable/detectable | 100.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 36:<25 IU/mL undetectable/detectable | 99.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 42:<25 IU/mL undetectable/detectable | 97.9 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Day 3:<100 IU/mL | 0.8 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 1:<100 IU/mL | 0.8 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 2:<100 IU/mL | 2.3 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 8:<100 IU/mL | 37.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 16:<100 IU/mL | 84.5 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 20:<100 IU/mL | 93.8 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 28:<100 IU/mL | 100.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 36:<100 IU/mL | 100.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 42:<100 IU/mL | 100.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Day 3:> or = 2 log10 change from baseline | 14.1 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 1:> or = 2 log10 change from baseline | 13.7 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 2:> or = 2 log10 change from baseline | 35.4 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 8:> or = 2 log10 change from baseline | 87.4 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 16:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 20:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 28:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With On-treatment Virologic Response at All Time Points | Week 36:> or = 2 log10 change from baseline | 100.0 Percentage of Participants |
Secondary
The Percentage of Participants With Partial Response
The table below shows the percentage of participants with partial response, defined as =\>2 log10 reduction in Hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment.
Time frame: Week 12
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 150mg 12Wks PR24/48 | The Percentage of Participants With Partial Response | 10.5 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With Partial Response | 0 Percentage of Participants |
Secondary
The Percentage of Participants With Viral Breakthrough
The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), 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 (\<25 IU/mL undetectable).
Time frame: Up to Week 48
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 150mg 12Wks PR24/48 | The Percentage of Participants With Viral Breakthrough | 0.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With Viral Breakthrough | 2.3 Percentage of Participants |
Secondary
The Percentage of Participants With Viral Breakthrough at Different Time Points
The table below shows the percentage of participants at different time points 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 (ie, lowest value measured in between baseline and current value), 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 (\<25 IU/mL undetectable).
Time frame: Up to Week 48
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 150mg 12Wks PR24/48 | The Percentage of Participants With Viral Breakthrough at Different Time Points | =<12 weeks | 1.9 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With Viral Breakthrough at Different Time Points | >12-=<24 weeks | 0.0 Percentage of Participants |
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With Viral Breakthrough at Different Time Points | >24 weeks | 10.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With Viral Breakthrough at Different Time Points | =<12 weeks | 0.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With Viral Breakthrough at Different Time Points | >12-=<24 weeks | 0.0 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With Viral Breakthrough at Different Time Points | >24 weeks | 0.0 Percentage of Participants |
Secondary
The Percentage of Participants With Viral Relapse
The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (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.
Time frame: Up to 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 | Value (NUMBER) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | The Percentage of Participants With Viral Relapse | 18.9 Percentage of Participants |
| PBO 12Wks PR48 | The Percentage of Participants With Viral Relapse | 50.5 Percentage of Participants |
Secondary
Time From End-of-treatment to Viral Relapse
The table below shows the mean number of days to viral relapse, defined as participants having confirmed detectable plasma level of Hepatitis C Virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (\<25 IU/mL undetectable) at the end of treatment.
Time frame: Up to 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 | Value (MEAN) | Dispersion |
|---|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Time From End-of-treatment to Viral Relapse | 284.09 Days | Standard Error 6.56 |
| PBO 12Wks PR48 | Time From End-of-treatment to Viral Relapse | 115.22 Days | Standard Error 6.72 |
Secondary
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
The table below shows mean time in days to reach HCV RNA levels \<1000 IU/mL.
Time frame: Up to Week 48
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 (MEDIAN) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL | 4 Days |
| PBO 12Wks PR48 | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL | 57 Days |
Secondary
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
The table below shows mean time in days to reach HCV RNA levels \<100 IU/mL.
Time frame: Up to Week 48
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 (MEDIAN) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL | 8 Days |
| PBO 12Wks PR48 | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL | 85 Days |
Secondary
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
The table below shows mean time in days to reach HCV RNA levels \<25 IU/mL undetectable or detectable.
Time frame: Up to Week 48
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 (MEDIAN) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable | 28 Days |
| PBO 12Wks PR48 | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable | 141 Days |
Secondary
Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
The table below shows mean time in days to reach HCV RNA levels \<25 IU/mL undetectable or detectable.
Time frame: Up to Week 48
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 (MEDIAN) |
|---|---|---|
| TMC435 150mg 12Wks PR24/48 | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable | 14 Days |
| PBO 12Wks PR48 | Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable | 110 Days |