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A Study of TMC435 in Combination With Pegylated Interferon Alp\Fa-2a and Ribavirin in Patients Infected With Genotype 1 Hepatitis C Virus Who Never Received Treatment (PILLAR)

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ClinicalTrials.gov Identifier: NCT00882908
Recruitment Status : Completed
First Posted : April 17, 2009
Results First Posted : June 16, 2014
Last Update Posted : June 16, 2014
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hepatitis C
Interventions Drug: TMC435
Drug: Ribavirin (R)
Drug: PegIFNα-2a (P)
Drug: Placebo
Enrollment 386
Recruitment Details The study was conducted at 79 sites in 13 countries: Australia, New Zealand, Canada, Austria, Belgium, Germany, Spain, France, Poland, Russia, Norway, Denmark, and the United States. Approximately 68% of participants were enrolled in Europe, 21% in North America, and 11% in Australia/New Zealand.
Pre-assignment Details In total, 506 participants were screened; 388 participants were randomized of whom 386 participants started treatment. Two randomized participants did not start treatment due to withdrawal of consent.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Period Title: Overall Study
Started 78 75 77 79 77
Completed 75 69 70 72 71
Not Completed 3 6 7 7 6
Reason Not Completed
Adverse Event             0             0             1             0             1
Lost to Follow-up             3             5             3             1             2
Protocol Violation             0             1             0             0             0
Withdrawal by Subject             0             0             3             5             2
Subject reached a virologic endpoint             0             0             0             0             1
Study terminated in error             0             0             0             1             0
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48 Total
Hide Arm/Group Description Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48. Total of all reporting groups
Overall Number of Baseline Participants 78 75 77 79 77 386
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 78 participants 75 participants 77 participants 79 participants 77 participants 386 participants
47
(19 to 66)
46
(18 to 67)
47
(18 to 69)
47
(18 to 69)
45
(21 to 67)
46.5
(18 to 69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants 75 participants 77 participants 79 participants 77 participants 386 participants
Female
38
  48.7%
28
  37.3%
34
  44.2%
35
  44.3%
38
  49.4%
173
  44.8%
Male
40
  51.3%
47
  62.7%
43
  55.8%
44
  55.7%
39
  50.6%
213
  55.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 78 participants 75 participants 77 participants 79 participants 77 participants 386 participants
Asia Pacific 9 9 7 13 4 42
Europe 52 52 56 44 58 262
North-America 17 14 14 22 15 82
1.Primary Outcome
Title The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Percentage of participants
80.8 70.7 77.9 84.8 64.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TMC435 75 mg 12 Wks + PR 24/48, TMC435 75 mg 24 Wks + PR 24/48, Placebo 24 Wks + PR48
Comments TMC435 75 mg 12 and 24 week treatment groups were pooled and the percentage of participants acheiving SVRW72 were compared with the percentage of participants acheiving SVRW72 in the placebo treatment group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.051
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions of SVRW72
Estimated Value 13.0
Confidence Interval (2-Sided) 97.5%
-1.9 to 28.0
Estimation Comments Difference in percentages of participants in the TMC435 75mg and placebo groups with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72 estimated from the logistic regression model.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TMC435 150 mg 12 Wks + PR 24/48, TMC435 150 mg 24 Wks + PR 24/48, Placebo 24 Wks + PR48
Comments TMC/PR 150 mg 12 and 24 week treatment groups were pooled and the percentage of participants achieving SVRW72 was compared the percentage of participants achieving SVRW72 in the placebo treatment group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in proportions of SVRW72
Estimated Value 18.9
Confidence Interval (2-Sided) 97.5%
4.4 to 33.5
Estimation Comments Difference in percentages of participants in the TMC435 150mg and placebo groups with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72 estimated from the logistic regression model.
2.Secondary Outcome
Title The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up
Hide Description The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels of less than 25 IU/mL undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
Time Frame Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Percentage of participants
Week 2 39.7 30.7 23.4 39.2 2.6
Week 4 75.6 68.0 75.3 74.7 5.2
Week 8 87.2 90.7 92.2 93.7 26.0
Week 12 91.0 93.3 93.5 94.9 55.8
Week 24 92.3 93.3 84.4 87.3 77.9
Week 36 85.9 81.3 81.8 84.8 76.6
Week 48 79.5 77.3 79.2 82.3 74.0
Week 60 79.5 68.0 75.3 83.5 63.6
Week 72 79.5 70.7 77.9 82.3 64.9
EOT (up to Week 24 or 48) 92.3 97.3 92.2 93.7 79.2
3.Secondary Outcome
Title The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up
Hide Description The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA less than 25 IU/mL detectable or undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
Time Frame Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Percentage of participants
Week 2 65.4 66.7 75.3 78.5 5.2
Week 4 85.9 88.0 90.9 91.1 15.6
Week 8 93.6 94.7 93.5 93.7 49.4
Week 12 93.6 94.7 96.1 94.9 66.2
Week 24 92.3 93.3 84.4 89.9 80.5
Week 36 85.9 81.3 81.8 84.8 79.2
Week 48 79.5 77.3 79.2 82.3 75.3
Week 60 79.5 68.0 75.3 83.5 64.9
Week 72 79.5 70.7 77.9 83.5 64.9
EOT (up to Week 24 or 48) 93.6 97.3 92.2 96.2 83.1
4.Secondary Outcome
Title The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment
Hide Description The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA greater than or equal to 2 log10 drop from Baseline at selected time points during treatment.
Time Frame Baseline (Day 1) and Weeks, 2, 4, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Percentage of participants
Week 2 93.6 98.7 97.4 98.7 40.3
Week 4 94.9 98.7 97.4 93.7 71.4
Week 8 97.4 97.3 97.4 94.9 84.4
Week 12 97.4 96.0 96.1 96.2 89.6
5.Secondary Outcome
Title The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Hide Description The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 24 weeks after the EOT.
Time Frame Week 48 or 72
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Percentage of participants
82.1 74.7 80.5 86.1 64.9
6.Secondary Outcome
Title The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Percentage of participants
75.6 68.0 75.3 74.7 5.2
7.Secondary Outcome
Title The Percentage of Participants Achieving an Early Virologic Response (EVR)
Hide Description 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 2 log10 at Week 12.
Time Frame Baseline (Day 1) and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Percentage of participants
97.4 96.0 96.1 96.2 89.6
8.Secondary Outcome
Title The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Percentage of participants
91.0 93.3 93.5 94.9 55.8
9.Secondary Outcome
Title The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Hide Description The table below shows the percentage of participants who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the EOT.
Time Frame Up to Week 36 or 52
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Percentage of participants
83.3 76.0 80.5 86.1 66.2
10.Secondary Outcome
Title Number of Participants With Viral Breakthrough
Hide Description The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period of the study, defined as a confirmed increase of more than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA more than 100 IU/mL in participants whose plasma HCV RNA level had previously been below the limit of quantification (less than 25 IU/mL detectable or undetectable).
Time Frame Week 24 or 48
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Participants
5 2 6 2 4
11.Secondary Outcome
Title The Number of Participants With Viral Relapse
Hide Description The table below shows the number of participants who experienced viral relapse, defined as a confirmed detectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level 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
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Number of Participants Analyzed 78 75 77 79 77
Measure Type: Number
Unit of Measure: Participants
8 14 6 6 11
12.Secondary Outcome
Title The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)
Hide Description The table below shows the number of participants with abnormal ALT levels at Baseline who achieved ALT levels within the normal range at the EOT.
Time Frame Baseline (Day 1) up to Week 24 or 48
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 All TMC435 Treatment Groups
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants in all 4 TMC435 treatment groups combined.
Overall Number of Participants Analyzed 43 45 48 43 179
Measure Type: Number
Unit of Measure: Participants
39 37 39 35 150
13.Secondary Outcome
Title Plasma Concentrations of TMC435
Hide Description The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for participants in each of the 4 TMC435 treatment groups.
Time Frame Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication with at least 1 post-baseline pharmacokinetic (PK) assessment were included in the PK analysis population.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Overall Number of Participants Analyzed 77 75 77 78
Median (Full Range)
Unit of Measure: ng/mL
Coh
240.9
(0 to 1927)
213.6
(40 to 2124)
1123.3
(91 to 13771)
1176.7
(0 to 9875)
Css, av
413.6
(6 to 2091)
374.0
(151 to 2385)
1661.8
(123 to 15868)
1501.6
(47 to 11648)
14.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
Hide Description The table below shows the median (range) AUC24h values for TMC435 for participants in each of the 4 TMC435 treatment groups. Two blood samples taken at least 2 hours apart from each other for determination of TMC435 plasma pharmacokinetics were obtained in all participants on Weeks 2, 4, 8, 12, 16, and 24 to obtain Bayesian estimates of TMC435 AUC24h (overall exposure).
Time Frame Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose of study medication with at least 1 post-baseline pharmacokinetic (PK) assessment were included in the PK analysis population.
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48
Hide Arm/Group Description:
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Overall Number of Participants Analyzed 77 75 77 78
Median (Full Range)
Unit of Measure: ng*h/mL
9926.4
(138 to 50179)
8976.8
(3615 to 57243)
39884.0
(2948 to 380830)
36038.8
(1134 to 279550)
Time Frame 72 weeks
Adverse Event Reporting Description All participants who received at least one dose of investigational medication included in safety analysis.
 
Arm/Group Title TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Hide Arm/Group Description Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48. Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
All-Cause Mortality
TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/78 (11.54%)   4/75 (5.33%)   4/77 (5.19%)   3/79 (3.80%)   10/77 (12.99%) 
Cardiac disorders           
Myocardial infarction † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Myopericarditis † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Endocrine disorders           
Hyperthyroidism † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Eye disorders           
Ocular vasculitis † 1  0/78 (0.00%)  1/75 (1.33%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Gastrointestinal disorders           
Abdominal pain upper † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  1/79 (1.27%)  0/77 (0.00%) 
Colitis † 1  0/78 (0.00%)  0/75 (0.00%)  1/77 (1.30%)  0/79 (0.00%)  0/77 (0.00%) 
Nausea † 1  0/78 (0.00%)  1/75 (1.33%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Small intestinal obstruction † 1  0/78 (0.00%)  1/75 (1.33%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Vomiting † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
General disorders           
Malaise † 1  0/78 (0.00%)  0/75 (0.00%)  1/77 (1.30%)  0/79 (0.00%)  0/77 (0.00%) 
Asthenia † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Hepatobiliary disorders           
Cholecystitis † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Infections and infestations           
Incision site cellulitis † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Necrotising fasciitis † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Perihepatic abscess † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  1/79 (1.27%)  0/77 (0.00%) 
Pneumonia pneumococcal † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Upper respiratory tract infection † 1  0/78 (0.00%)  1/75 (1.33%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Appendicitis † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Subcutaneous abscess † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Vulval abscess † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Injury, poisoning and procedural complications           
Post procedural bile leak † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  1/79 (1.27%)  0/77 (0.00%) 
Metabolism and nutrition disorders           
Malnutrition † 1  0/78 (0.00%)  0/75 (0.00%)  1/77 (1.30%)  0/79 (0.00%)  0/77 (0.00%) 
Type 1 diabetes mellitus † 1  0/78 (0.00%)  0/75 (0.00%)  1/77 (1.30%)  0/79 (0.00%)  0/77 (0.00%) 
Musculoskeletal and connective tissue disorders           
Intervertebral disc protrusion † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Spinal disorder † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Myositis † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Breast cancer † 1  0/78 (0.00%)  0/75 (0.00%)  1/77 (1.30%)  0/79 (0.00%)  0/77 (0.00%) 
Parathyroid tumour benign † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Ovarian neoplasm † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Nervous system disorders           
Headache † 1  0/78 (0.00%)  1/75 (1.33%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Psychiatric disorders           
Depression † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  1/79 (1.27%)  0/77 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Haemoptysis † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Chronic obstructive pulmonary disease † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  1/77 (1.30%) 
Skin and subcutaneous tissue disorders           
Cutaneous vasculitis † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  0/79 (0.00%)  0/77 (0.00%) 
Vascular disorders           
Hypertension † 1  0/78 (0.00%)  0/75 (0.00%)  0/77 (0.00%)  1/79 (1.27%)  0/77 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TMC435 75 mg 12 Wks + PR 24/48 TMC435 75 mg 24 Wks + PR 24/48 TMC435 150 mg 12 Wks + PR 24/48 TMC435 150 mg 24 Wks + PR 24/48 Placebo 24 Wks + PR48
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   76/78 (97.44%)   75/75 (100.00%)   74/77 (96.10%)   77/79 (97.47%)   75/77 (97.40%) 
Blood and lymphatic system disorders           
Neutropenia † 1  15/78 (19.23%)  23/75 (30.67%)  19/77 (24.68%)  18/79 (22.78%)  16/77 (20.78%) 
Anaemia † 1  15/78 (19.23%)  16/75 (21.33%)  17/77 (22.08%)  15/79 (18.99%)  16/77 (20.78%) 
Leukopenia † 1  2/78 (2.56%)  1/75 (1.33%)  1/77 (1.30%)  6/79 (7.59%)  4/77 (5.19%) 
Ear and labyrinth disorders           
Vertigo † 1  5/78 (6.41%)  1/75 (1.33%)  3/77 (3.90%)  4/79 (5.06%)  4/77 (5.19%) 
Endocrine disorders           
Hypothyroidism † 1  6/78 (7.69%)  1/75 (1.33%)  1/77 (1.30%)  1/79 (1.27%)  5/77 (6.49%) 
Eye disorders           
Dry eye † 1  3/78 (3.85%)  2/75 (2.67%)  3/77 (3.90%)  4/79 (5.06%)  4/77 (5.19%) 
Vision blurred † 1  3/78 (3.85%)  1/75 (1.33%)  5/77 (6.49%)  3/79 (3.80%)  1/77 (1.30%) 
Gastrointestinal disorders           
Nausea † 1  26/78 (33.33%)  16/75 (21.33%)  20/77 (25.97%)  24/79 (30.38%)  21/77 (27.27%) 
Diarrhoea † 1  12/78 (15.38%)  14/75 (18.67%)  11/77 (14.29%)  10/79 (12.66%)  12/77 (15.58%) 
Vomiting † 1  5/78 (6.41%)  3/75 (4.00%)  6/77 (7.79%)  8/79 (10.13%)  5/77 (6.49%) 
Dry mouth † 1  5/78 (6.41%)  7/75 (9.33%)  3/77 (3.90%)  6/79 (7.59%)  7/77 (9.09%) 
Abdominal pain upper † 1  5/78 (6.41%)  4/75 (5.33%)  6/77 (7.79%)  4/79 (5.06%)  4/77 (5.19%) 
Dyspepsia † 1  4/78 (5.13%)  5/75 (6.67%)  4/77 (5.19%)  6/79 (7.59%)  6/77 (7.79%) 
Constipation † 1  6/78 (7.69%)  1/75 (1.33%)  7/77 (9.09%)  2/79 (2.53%)  5/77 (6.49%) 
Abdominal pain † 1  4/78 (5.13%)  3/75 (4.00%)  4/77 (5.19%)  3/79 (3.80%)  4/77 (5.19%) 
Aphthous stomatitis † 1  2/78 (2.56%)  1/75 (1.33%)  4/77 (5.19%)  2/79 (2.53%)  3/77 (3.90%) 
General disorders           
Fatigue † 1  26/78 (33.33%)  35/75 (46.67%)  32/77 (41.56%)  38/79 (48.10%)  37/77 (48.05%) 
Influenza like illness † 1  21/78 (26.92%)  32/75 (42.67%)  18/77 (23.38%)  27/79 (34.18%)  29/77 (37.66%) 
Pyrexia † 1  18/78 (23.08%)  15/75 (20.00%)  15/77 (19.48%)  16/79 (20.25%)  13/77 (16.88%) 
Asthenia † 1  20/78 (25.64%)  12/75 (16.00%)  18/77 (23.38%)  13/79 (16.46%)  16/77 (20.78%) 
Irritability † 1  10/78 (12.82%)  7/75 (9.33%)  14/77 (18.18%)  11/79 (13.92%)  8/77 (10.39%) 
Chills † 1  4/78 (5.13%)  8/75 (10.67%)  6/77 (7.79%)  7/79 (8.86%)  8/77 (10.39%) 
Injection site erythema † 1  4/78 (5.13%)  8/75 (10.67%)  5/77 (6.49%)  7/79 (8.86%)  4/77 (5.19%) 
Injection site reaction † 1  5/78 (6.41%)  4/75 (5.33%)  2/77 (2.60%)  2/79 (2.53%)  4/77 (5.19%) 
Pain † 1  6/78 (7.69%)  2/75 (2.67%)  2/77 (2.60%)  1/79 (1.27%)  2/77 (2.60%) 
Hepatobiliary disorders           
Hyperbilirubinaemia † 1  2/78 (2.56%)  0/75 (0.00%)  5/77 (6.49%)  2/79 (2.53%)  2/77 (2.60%) 
Infections and infestations           
Nasopharyngitis † 1  1/78 (1.28%)  5/75 (6.67%)  4/77 (5.19%)  4/79 (5.06%)  6/77 (7.79%) 
Influenza † 1  1/78 (1.28%)  5/75 (6.67%)  4/77 (5.19%)  3/79 (3.80%)  3/77 (3.90%) 
Urinary tract infection † 1  2/78 (2.56%)  2/75 (2.67%)  1/77 (1.30%)  5/79 (6.33%)  2/77 (2.60%) 
Sinusitis † 1  4/78 (5.13%)  0/75 (0.00%)  1/77 (1.30%)  2/79 (2.53%)  2/77 (2.60%) 
Investigations           
Weight decreased † 1  7/78 (8.97%)  3/75 (4.00%)  3/77 (3.90%)  6/79 (7.59%)  3/77 (3.90%) 
Neutrophil count decreased † 1  1/78 (1.28%)  5/75 (6.67%)  5/77 (6.49%)  4/79 (5.06%)  4/77 (5.19%) 
Blood bilirubin increased † 1  1/78 (1.28%)  0/75 (0.00%)  5/77 (6.49%)  5/79 (6.33%)  0/77 (0.00%) 
Alanine aminotransferase increased † 1  3/78 (3.85%)  1/75 (1.33%)  1/77 (1.30%)  5/79 (6.33%)  0/77 (0.00%) 
Aspartate aminotransferase increased † 1  2/78 (2.56%)  1/75 (1.33%)  1/77 (1.30%)  6/79 (7.59%)  0/77 (0.00%) 
Gamma-glutamyltransferase increased † 1  1/78 (1.28%)  0/75 (0.00%)  0/77 (0.00%)  4/79 (5.06%)  0/77 (0.00%) 
Metabolism and nutrition disorders           
Anorexia † 1  10/78 (12.82%)  12/75 (16.00%)  11/77 (14.29%)  9/79 (11.39%)  11/77 (14.29%) 
Decreased appetite † 1  6/78 (7.69%)  3/75 (4.00%)  4/77 (5.19%)  4/79 (5.06%)  6/77 (7.79%) 
Musculoskeletal and connective tissue disorders           
Myalgia † 1  17/78 (21.79%)  12/75 (16.00%)  16/77 (20.78%)  10/79 (12.66%)  17/77 (22.08%) 
Arthralgia † 1  11/78 (14.10%)  12/75 (16.00%)  14/77 (18.18%)  16/79 (20.25%)  11/77 (14.29%) 
Back pain † 1  5/78 (6.41%)  8/75 (10.67%)  10/77 (12.99%)  7/79 (8.86%)  7/77 (9.09%) 
Muscle spasms † 1  4/78 (5.13%)  2/75 (2.67%)  1/77 (1.30%)  4/79 (5.06%)  4/77 (5.19%) 
Musculoskeletal pain † 1  1/78 (1.28%)  4/75 (5.33%)  0/77 (0.00%)  3/79 (3.80%)  6/77 (7.79%) 
Pain in extremity † 1  1/78 (1.28%)  1/75 (1.33%)  1/77 (1.30%)  3/79 (3.80%)  5/77 (6.49%) 
Nervous system disorders           
Headache † 1  41/78 (52.56%)  34/75 (45.33%)  35/77 (45.45%)  32/79 (40.51%)  40/77 (51.95%) 
Dizziness † 1  10/78 (12.82%)  3/75 (4.00%)  4/77 (5.19%)  12/79 (15.19%)  6/77 (7.79%) 
Disturbance in attention † 1  5/78 (6.41%)  3/75 (4.00%)  6/77 (7.79%)  4/79 (5.06%)  3/77 (3.90%) 
Dysgeusia † 1  6/78 (7.69%)  1/75 (1.33%)  5/77 (6.49%)  4/79 (5.06%)  5/77 (6.49%) 
Paraesthesia † 1  1/78 (1.28%)  0/75 (0.00%)  4/77 (5.19%)  1/79 (1.27%)  1/77 (1.30%) 
Syncope † 1  1/78 (1.28%)  2/75 (2.67%)  2/77 (2.60%)  1/79 (1.27%)  4/77 (5.19%) 
Migraine † 1  0/78 (0.00%)  0/75 (0.00%)  1/77 (1.30%)  4/79 (5.06%)  0/77 (0.00%) 
Hypoaesthesia † 1  0/78 (0.00%)  0/75 (0.00%)  1/77 (1.30%)  1/79 (1.27%)  4/77 (5.19%) 
Psychiatric disorders           
Insomnia † 1  19/78 (24.36%)  14/75 (18.67%)  23/77 (29.87%)  13/79 (16.46%)  23/77 (29.87%) 
Depression † 1  8/78 (10.26%)  4/75 (5.33%)  9/77 (11.69%)  11/79 (13.92%)  14/77 (18.18%) 
Sleep disorder † 1  8/78 (10.26%)  3/75 (4.00%)  4/77 (5.19%)  7/79 (8.86%)  4/77 (5.19%) 
Mood altered † 1  4/78 (5.13%)  5/75 (6.67%)  1/77 (1.30%)  8/79 (10.13%)  7/77 (9.09%) 
Depressed mood † 1  4/78 (5.13%)  4/75 (5.33%)  3/77 (3.90%)  6/79 (7.59%)  3/77 (3.90%) 
Anxiety † 1  5/78 (6.41%)  2/75 (2.67%)  4/77 (5.19%)  4/79 (5.06%)  5/77 (6.49%) 
Mood swings † 1  4/78 (5.13%)  0/75 (0.00%)  1/77 (1.30%)  5/79 (6.33%)  3/77 (3.90%) 
Respiratory, thoracic and mediastinal disorders           
Cough † 1  18/78 (23.08%)  9/75 (12.00%)  12/77 (15.58%)  13/79 (16.46%)  15/77 (19.48%) 
Dyspnoea † 1  12/78 (15.38%)  8/75 (10.67%)  7/77 (9.09%)  6/79 (7.59%)  6/77 (7.79%) 
Dyspnoea exertional † 1  6/78 (7.69%)  9/75 (12.00%)  10/77 (12.99%)  5/79 (6.33%)  7/77 (9.09%) 
Oropharyngeal pain † 1  5/78 (6.41%)  3/75 (4.00%)  4/77 (5.19%)  4/79 (5.06%)  8/77 (10.39%) 
Skin and subcutaneous tissue disorders           
Pruritus † 1  25/78 (32.05%)  17/75 (22.67%)  30/77 (38.96%)  24/79 (30.38%)  35/77 (45.45%) 
Rash † 1  21/78 (26.92%)  10/75 (13.33%)  16/77 (20.78%)  18/79 (22.78%)  18/77 (23.38%) 
Dry skin † 1  12/78 (15.38%)  12/75 (16.00%)  17/77 (22.08%)  22/79 (27.85%)  14/77 (18.18%) 
Alopecia † 1  20/78 (25.64%)  11/75 (14.67%)  11/77 (14.29%)  11/79 (13.92%)  16/77 (20.78%) 
Erythema † 1  3/78 (3.85%)  2/75 (2.67%)  5/77 (6.49%)  5/79 (6.33%)  4/77 (5.19%) 
Eczema † 1  7/78 (8.97%)  1/75 (1.33%)  3/77 (3.90%)  3/79 (3.80%)  5/77 (6.49%) 
Pruritus generalised † 1  3/78 (3.85%)  2/75 (2.67%)  3/77 (3.90%)  6/79 (7.59%)  5/77 (6.49%) 
Night sweats † 1  6/78 (7.69%)  1/75 (1.33%)  1/77 (1.30%)  2/79 (2.53%)  1/77 (1.30%) 
Dermatitis † 1  1/78 (1.28%)  4/75 (5.33%)  1/77 (1.30%)  1/79 (1.27%)  1/77 (1.30%) 
Hyperhidrosis † 1  1/78 (1.28%)  3/75 (4.00%)  0/77 (0.00%)  3/79 (3.80%)  4/77 (5.19%) 
Vascular disorders           
Hot flush † 1  1/78 (1.28%)  0/75 (0.00%)  2/77 (2.60%)  5/79 (6.33%)  2/77 (2.60%) 
Hypertension † 1  0/78 (0.00%)  1/75 (1.33%)  1/77 (1.30%)  4/79 (5.06%)  2/77 (2.60%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA Version 12.0
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Global Clinical Development Manager
Organization: Jan-Cil France
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00882908     History of Changes
Other Study ID Numbers: CR015799
TMC435-TiDP16-C205 ( Other Identifier: Tibotec Pharmaceuticals, Ireland )
2008-007147-13 ( EudraCT Number )
First Submitted: April 16, 2009
First Posted: April 17, 2009
Results First Submitted: December 18, 2013
Results First Posted: June 16, 2014
Last Update Posted: June 16, 2014