QUEST-1: An Efficacy, Safety, and Tolerability Study of TMC435 in Treatment-naive, Genotype 1 Hepatitis C-infected Patients

• Sponsor: Janssen R&D Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01289782
• Collaborator: (none)
• Enrollment: 395
• Locations: 63
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 6.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in participants who are infected with genotype 1 hepatitis C virus who have never received treatment before. Participants will also receive peginterferon alpha-2a and ribavirin as part of their treatment.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: Placebo; Drug: TMC435; Drug: Peginterferon alpha-2a (PegIFN alpha-2a); Drug: Ribavirin (RBV)	Phase 3

Detailed Description

This is a randomized, double-blind (neither physician nor participants know the name of the assigned drug), placebo-controlled study of TMC435 in participants who are infected with genotype 1 hepatitis C virus (HCV), who have never received treatment for HCV infection before. Participants in this study will also receive two other drugs for their HCV infection called peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV). The purpose of the study is to investigate if TMC435 is superior to placebo in reducing plasma levels of HCV ribonucleic acid (RNA) to an undetectable level 12 weeks after the end of treatment. For the first 12 weeks, participants will take either TMC435 or placebo, plus PegIFNα-2a and RBV. For the next 12 weeks, participants will take PegIFN alpha-2a and RBV only. After that, some participants will continue to take PegIFN alpha-2a and RBV for up to 24 additional weeks and some will stop taking PegIFN alpha-2a and RBV depending on response-guided treatment criteria. The study doctor will inform each participant about how to take their study medication and when they should stop taking it. After a participant 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). Participants will be monitored for safety throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 395 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy, Safety and Tolerability of TMC435 vs Placebo as Part of a Treatment Regimen Including Peginterferon α-2a and Ribavirin in Treatment-naïve, Genotype 1 Hepatitis Cinfected Subjects
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TMC435 TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alpha-2a (PegIFN alpha-2a) and ribavirin (RBV) for 24 or 48 weeks	Drug: TMC435; 150 mg capsule once daily for 12 weeks in addition to PegIFN alpha-2a and RBV for 24 or 48 weeks; Drug: Peginterferon alpha-2a (PegIFN alpha-2a); One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFN alpha-2a once weekly for up to 48 weeks.; Other Names: Pegasys ; Drug: Ribavirin (RBV); 200-mg tablets of RBV (body-weight adjusted dose) taken orally (by mouth) twice daily for up to 48 weeks.; Other Names: Copegus
Placebo Comparator: Placebo Placebo 150 mg capsule once daily for 12 weeks in addition to PegIFNα-2a and RBV for 48 weeks	Drug: Placebo; 150 mg capsule once daily for 12 weeks in addition to PegIFN alpha-2a and RBV for 48 weeks; Drug: Peginterferon alpha-2a (PegIFN alpha-2a); One subcutaneous (under the skin) injection containing 0.5 mL solution with 180 mcg PegIFN alpha-2a once weekly for up to 48 weeks.; Other Names: Pegasys ; Drug: Ribavirin (RBV); 200-mg tablets of RBV (body-weight adjusted dose) taken orally (by mouth) twice daily for up to 48 weeks.; Other Names: Copegus

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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 the change from baseline in log10 HCV RNA levels.

5. 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.

6. 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 Hepatitis C virus (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, < 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.

7. 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.

8. 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.

9. 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.

10. The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR) [Week 4 and 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.

11. 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.

12. 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.

13. 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.

14. Percentage of Participants With Partial Response [Week 12]

    The table below shows the percentage of participants with partial response, defined as greater than or equal to 2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment.

15. 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).

16. 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.

17. 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.

18. 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.

19. Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable [Up to Week 48]

    The table below shows median time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable.

20. Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable [Up to Week 48]

    The table below shows median time in days to reach HCV RNA levels <25 IU/mL undetectable.

21. Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL [Up to Week 48]

    The table below shows median time in days to reach HCV RNA levels <100 IU/mL.

22. Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL [Up to Week 48]

    The table below shows median time in days to reach HCV RNA levels <1000 IU/mL.

23. 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).

24. 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.

25. 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, 158 of 264 participants in the TMC435 treatment group and 89 of 130 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.

26. Median Time to Normalization of Alanine Aminotransferase (ALT) Levels [Up to Week 48]

    The table below shows the median time in weeks to normalization of ALT levels.

27. Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) [Fom the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 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 after dosing for TMC435 for all participants. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then a median AUC value calcuated across all visits for each participant. The median AUC value across all visits for each participant was used to calculate the mean AUC 24 hr all participants in the study.

28. Plasma Concentration of TMC435: Predose Plasma Concentration (C0h) [Before administration of TMC435 at Weeks 2, 4, 8, and 12]

    The table below shows the mean (standard deviation) values for the C0h of TMC435.To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then a median C0H value calculated across visits for each participant. The median COh value for each participant across all visits was used to calculate the mean C0h for the study.

29. Plasma Concentration of TMC435: Systemic Clearance (CL) [Across Weeks 2, 4, 8, and 12]

    The table below shows the mean (standard deviation) values for the CL of TMC435.To calculate the mean CL for all participants in the study, CL values were first derived for each participant at each visit and then a median CL value calculated across visits for each participant. The median CL value for each participant was used to calculate the mean CL for all participants in the study.

30. Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores [Baseline to Week 60 and Week 72]

    Study participants completed FSS questionnaires during study visits before treatment began and throughout treatment and follow-up to rate the severity and impact of fatigue they experienced in the preceding 2 weeks on their daily lives. FSS total scores are the average of nine questions with a range from 1 [no fatigue] to 7 [worst possible fatigue]. An area under the curve (AUC) analysis compared the overall severity of fatigue in each treatment group from baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in the amount of fatigue participants experienced throughout the study resulting in equal AUC from baseline to Week 72 (AUC72) for FSS total scores. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) and the statistical comparison between treatment groups.

31. Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment [Baseline to Week 60 and Week 72]

    Impairment in overall work productivity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire completed by participants during study visits throughout the study. WPAI Overall Productivity Scores ranged from 0% to 100% (higher WPAI scores indicated greater impairment in productivity). An area under the curve (AUC) analysis compared the overall WPAI Overall Work Productivity Scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in the WPAI Overall Work Productivity Scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in WPAI Work Productivity Scores and the statistical comparison between treatment groups.

32. Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment [Baseline to Week 60 and Week 72]

    Impairment in daily activity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire, Question 6. Scores ranged from 0 (no effect on activities) to 10 (completely prevented me from doing my daily activities). An area under the curve (AUC) analysis compared the impairment in daily activity scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in impairment in daily activity scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in the impairment in daily activity scores and the statistical comparison between treatment groups.

33. Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) in Work Productivity and Activity (WPAI) Absenteeism Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment [Baseline to Week 60 and Week 72]

    Time missed from work in hours because of HCV infection or its treatment was assessed by measuring the change from baseline in the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire Absenteeism score (time missed from work, question #2). The number of hours missed from work because of HCV was divided by the total number of hours supposed to work, and expressed as a percentage. An area under the curve (AUC) analysis compared the WPAI absenteeism scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms WPAI absenteeism scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in WPAI absenteeism scores and the statistical comparison between treatment groups.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Genotype 1 hepatitis C infection (confirmed at screening)

• Patient has not received any prior treatment for hepatitis C

• Patient must have had a 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Dothan	Alabama	United States
2		Hoover	Alabama	United States
3		Phoenix	Arizona	United States
4		Bakersfield	California	United States
5		Coronado	California	United States
6		Long Beach	California	United States
7		San Diego	California	United States
8		Aurora	Colorado	United States
9		Englewood	Colorado	United States
10		Miami	Florida	United States
11		Chicago	Illinois	United States
12		Jackson	Mississippi	United States
13		Tupelo	Mississippi	United States
14		Saint Louis	Missouri	United States
15		New York	New York	United States
16		Chapel Hill	North Carolina	United States
17		Cincinnati	Ohio	United States
18		Philadelphia	Pennsylvania	United States
19		Nashville	Tennessee	United States
20		Dallas	Texas	United States
21		Houston	Texas	United States
22		San Antonio	Texas	United States
23		Darlinghurst		Australia
24		Fitzroy		Australia
25		Kingswood		Australia
26		Melbourne		Australia
27		Sydney		Australia
28		Wolloongabba		Australia
29		Calgary	Alberta	Canada
30		Ottawa	Ontario	Canada
31		Toronto	Ontario	Canada
32		Montreal	Quebec	Canada
33		Berlin		Germany
34		Heidelberg		Germany
35		Kiel		Germany
36		Tübingen		Germany
37		Guadalajara		Mexico
38		Mex Ctity		Mexico
39		Monterrey		Mexico
40		Auckland		New Zealand
41		Christchurch		New Zealand
42		Hamilton		New Zealand
43		San Juan		Puerto Rico
44		Bucuresti		Romania
45		Moscow		Russian Federation
46		Nizhny Novgorod		Russian Federation
47		Saint-Petersburg		Russian Federation
48		Samara		Russian Federation
49		Smolensk		Russian Federation
50		St Petersburg		Russian Federation
51		Barcelona		Spain
52		Madrid		Spain
53		Sevilla N/A		Spain
54		Valencia		Spain
55		Donetsk		Ukraine
56		Kiev		Ukraine
57		Kyiv		Ukraine
58		Vinnytsia		Ukraine
59		Derby		United Kingdom
60		Liverpool		United Kingdom
61		London		United Kingdom
62		Nottingham		United Kingdom
63		Plymouth		United Kingdom

Sponsors and Collaborators

• Janssen R&D Ireland

Investigators

• Study Director: Janssen R&D Ireland Clinical Trial, Janssen R&D Ireland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen R&D Ireland
• ClinicalTrials.gov Identifier: NCT01289782
• Other Study ID Numbers: CR017386; TMC435-TiDP16-C208
• First Posted: Feb 4, 2011
• Last Update Posted: Jun 4, 2014
• Last Verified: May 1, 2014

• Keywords provided by Janssen R&D Ireland: Hepatitis C; TMC435; HCV; Hep C; Genotype 1
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Ribavirin; Peginterferon alfa-2a; Simeprevir

Study Results

Participant Flow

Recruitment Details	The study was conducted from 18 January 2011 to 29 January 2013. The study was conducted at 71 sites in 13 countries.
Pre-assignment Detail	395 participants were randomly allocated to the 2 treatment arms. 394 participants received at least 1 dose of study medication and were included in the intent-to-treat analysis set.

Arm/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Period Title: Overall Study
STARTED	264	130
COMPLETED	239	118
NOT COMPLETED	25	12

Baseline Characteristics

Arm/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48	Total
Arm/Group Description	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).	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).	Total of all reporting groups
Overall Participants	264	130	394
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	48	48	48
Sex: Female, Male (Count of Participants)
Female	116 43.9%	56 43.1%	172 43.7%
Male	148 56.1%	74 56.9%	222 56.3%

Outcome Measures

1. Primary Outcome

Title	The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	79.5 30.1%	50 38.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	Null hypothesis: There is no difference in proportions of SVR12 between the treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions of SVR12
	Estimated Value	29.3
	Confidence Interval	(2-Sided) 95%; 20.1 to 38.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	78.4 29.7%	49.2 37.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	There is no difference in proportions of SVRW72 between the treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions of SVRW72
	Estimated Value	28.9
	Confidence Interval	(2-Sided) 95%; 19.6 to 38.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	79.5 30.1%	49.2 37.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	There is no difference in proportions of SVR24 between the treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions of SVR24
	Estimated Value	30.1
	Confidence Interval	(2-Sided) 95%; 20.8 to 39.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	The Percentage of Participants Who Achieved a Sustained Virologic Response 4 Weeks After the Planned End of Treatment (SVR4)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	82.2 31.1%	56.2 43.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	There is no difference in proportions of SVR4 between the treatment groups.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions of SVR4
	Estimated Value	25.8
	Confidence Interval	(2-Sided) 95%; 16.8 to 34.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Description	The table below shows the change from baseline in log10 HCV RNA levels.
Time Frame	Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Day 3	-3.52 (0.0459)	-0.93 (0.0774)
Week 1	-4.47 (0.0512)	-1.08 (0.0835)
Week 4	-5.22 (0.0552)	-2.56 (0.1434)
Week 12	-5.34 (0.0524)	-4.18 (0.1510)
Week 24	-5.32 (0.0604)	-4.89 (0.1289)
Week 48	-5.33 (0.2605)	-5.23 (0.1670)

6. Secondary Outcome

Title	Actual Values of log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Description	The table below shows actual values of log10 HCV RNA levels.
Time Frame	Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Day 3	2.914 (0.052)	5.351 (0.104)
Week 1	1.973 (0.052)	5.202 (0.114)
Week 4	1.223 (0.049)	3.723 (0.159)
Week 12	1.090 (0.041)	2.111 (0.155)
Week 24	1.113 (0.050)	1.334 (0.110)
Week 48	0.993 (0.039)	0.961 (0.006)

7. Secondary Outcome

Title	Percentage of Participants With On-treatment Virologic Response at All Time Points
Description	The table below shows the percentage of participants with Hepatitis C virus (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, < 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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Day 3:<25 IU/mL undetectable	0.4 0.2%	0.8 0.6%
Week 1:<25 IU/mL undetectable	6.6 2.5%	0.8 0.6%
Week 2:<25 IU/mL undetectable	35.8 13.6%	2.3 1.8%
Week 8:<25 IU/mL undetectable	90.0 34.1%	26.2 20.2%
Week 16:<25 IU/mL undetectable	93.8 35.5%	69.2 53.2%
Week 20:<25 IU/mL undetectable	93.4 35.4%	78.2 60.2%
Week 28:<25 IU/mL undetectable	90.9 34.4%	96.3 74.1%
Week 36:<25 IU/mL undetectable	90.9 34.4%	100.0 76.9%
Week 42:<25 IU/mL undetectable	90.9 34.4%	98.7 75.9%
Day 3:<25 IU/mL undetectable/detectable	2.4 0.9%	0.8 0.6%
Week 1:<25 IU/mL undetectable/detectable	36.8 13.9%	2.3 1.8%
Week 2:<25 IU/mL undetectable/detectable	76.7 29.1%	6.3 4.8%
Week 8:<25 IU/mL undetectable/detectable	94.0 35.6%	40.5 31.2%
Week 16:<25 IU/mL undetectable/detectable	95.4 36.1%	82.7 63.6%
Week 20:<25 IU/mL undetectable/detectable	95.0 36%	84.2 64.8%
Week 28:<25 IU/mL undetectable/detectable	100.0 37.9%	98.8 76%
Week 36:<25 IU/mL undetectable/detectable	100.0 37.9%	100.0 76.9%
Week 42:<25 IU/mL undetectable/detectable	100.0 37.9%	100.0 76.9%
Day 3:<100 IU/mL	11.4 4.3%	1.6 1.2%
Week 1:<100 IU/mL	62.8 23.8%	3.1 2.4%
Week 2:<100 IU/mL	85.2 32.3%	7.8 6%
Week 8:<100 IU/mL	94.8 35.9%	46.0 35.4%
Week 16:<100 IU/mL	96.7 36.6%	84.6 65.1%
Week 20:<100 IU/mL	96.7 36.6%	86.1 66.2%
Week 28:<100 IU/mL	100.0 37.9%	98.8 76%
Week 36:<100 IU/mL	100.0 37.9%	100.0 76.9%
Week 42:<100 IU/mL	100.0 37.9%	100.0 76.9%
Day 3:> or = 2 log10 change from baseline	95.3 36.1%	13.3 10.2%
Week 1:> or = 2 log10 change from baseline	98.1 37.2%	20.2 15.5%
Week 2:> or = 2 log10 change from baseline	98.8 37.4%	35.2 27.1%
Week 8:> or = 2 log10 change from baseline	98.4 37.3%	80.2 61.7%
Week 16:> or = 2 log10 change from baseline	100.0 37.9%	99.0 76.2%
Week 20:> or = 2 log10 change from baseline	98.3 37.2%	97.0 74.6%
Week 28:> or = 2 log10 change from baseline	100.0 37.9%	97.5 75%
Week 36:> or = 2 log10 change from baseline	100.0 37.9%	98.7 75.9%
Week 42:> or = 2 log10 change from baseline	100.0 37.9%	98.7 75.9%

8. Secondary Outcome

Title	The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	79.5 30.1%	11.8 9.1%

9. Secondary Outcome

Title	The Percentage of Participants Achieving a Early Virologic Response (EVR)
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 greater than or equal to 2 log10 at Week 12.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	99.2 37.6%	85.2 65.5%

10. Secondary Outcome

Title	The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	92.8 35.2%	50.8 39.1%

11. Secondary Outcome

Title	The Percentage of Participants Achieving a Extended Rapid Virologic Response (eRVR)
Description	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 12

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	78.9 29.9%	11.7 9%

12. Secondary Outcome

Title	The Percentage of Participants With <1 log10 Decrease in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) From Baseline at Week 4
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	0 0%	15.7 12.1%

13. Secondary Outcome

Title	Percentage of Participants With in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels >1000 IU/mL at Week 4
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	4.5 1.7%	63.8 49.1%

14. Secondary Outcome

Title	Percentage of Participants With Null Response
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	0.8 0.3%	14.8 11.4%

15. Secondary Outcome

Title	Percentage of Participants With Partial Response
Description	The table below shows the percentage of participants with partial response, defined as greater than or equal to 2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline, but not achieving undetectable HCV RNA while on treatment.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	3.2 1.2%	13.1 10.1%

16. Secondary Outcome

Title	Percentage of Participants With Viral Breakthrough
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	4.9 1.9%	7.7 5.9%

17. Secondary Outcome

Title	Percentage of Participants With Viral Relapse
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	9.0 3.4%	22.6 17.4%

18. Secondary Outcome

Title	Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	83 31.4%	NA NaN

19. Secondary Outcome

Title	Percentage of Participants With On-treatment Failure
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Number [Percentage of participants]	9.1 3.4%	33.8 26%

20. Secondary Outcome

Title	Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable or Detectable
Description	The table below shows median time in days to reach HCV RNA levels <25 IU/mL undetectable or detectable.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Median (95% Confidence Interval) [Days]	14 (1.25)	85 (4.89)

21. Secondary Outcome

Title	Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable
Description	The table below shows median time in days to reach HCV RNA levels <25 IU/mL undetectable.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Median (95% Confidence Interval) [Days]	28	111

22. Secondary Outcome

Title	Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
Description	The table below shows median time in days to reach HCV RNA levels <100 IU/mL.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Median (95% Confidence Interval) [Days]	28	84

23. Secondary Outcome

Title	Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
Description	The table below shows median time in days to reach HCV RNA levels <1000 IU/mL.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Median (95% Confidence Interval) [Days]	4	56.5

24. Secondary Outcome

Title	The Percentage of Participants With Viral Breakthrough at Different Time Points
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
< 12 Weeks	2.7 1%	1.5 1.2%
Week 12 - Week 24	2.5 0.9%	6.8 5.2%
> Week 24	0 0%	1.2 0.9%

25. Secondary Outcome

Title	Time From End-of-treatment to Viral Relapse
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	264	130
Mean (Standard Error) [Days]	100.96 (1.21)	146.04 (5.22)

26. Secondary Outcome

Title	The Percentage of Participants With Normalization of Alanine Aminotransferase (ALT)
Description	The percentage of participants analyzed were those with baseline ALT values out of the normal range (ie, 158 of 264 participants in the TMC435 treatment group and 89 of 130 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

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	158	89
Number [Percentage of participants]	81.0 30.7%	77.5 59.6%

27. Secondary Outcome

Title	Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
Description	The table below shows the median time in weeks to normalization of ALT levels.
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	158	89
Median (95% Confidence Interval) [Weeks]	2.14	8.14

28. Secondary Outcome

Title	Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h)
Description	The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing for TMC435 for all participants. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then a median AUC value calcuated across all visits for each participant. The median AUC value across all visits for each participant was used to calculate the mean AUC 24 hr all participants in the study.
Time Frame	Fom the time of administration up to 24 hours after dosing at Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	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).
Measure Participants	259
Mean (Standard Deviation) [ng*h/mL]	54795 (55627.3)

29. Secondary Outcome

Title	Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
Description	The table below shows the mean (standard deviation) values for the C0h of TMC435.To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then a median C0H value calculated across visits for each participant. The median COh value for each participant across all visits was used to calculate the mean C0h for the study.
Time Frame	Before administration of TMC435 at Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	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).
Measure Participants	259
Mean (Standard Deviation) [ng/mL]	1825 (2306.1)

30. Secondary Outcome

Title	Plasma Concentration of TMC435: Systemic Clearance (CL)
Description	The table below shows the mean (standard deviation) values for the CL of TMC435.To calculate the mean CL for all participants in the study, CL values were first derived for each participant at each visit and then a median CL value calculated across visits for each participant. The median CL value for each participant was used to calculate the mean CL for all participants in the study.
Time Frame	Across Weeks 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48
Arm/Group Description	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).
Measure Participants	259
Mean (Standard Deviation) [L/h]	5.05 (3.319)

31. Secondary Outcome

Title	Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for the Fatigue Severity Scale (FSS) Total Scores
Description	Study participants completed FSS questionnaires during study visits before treatment began and throughout treatment and follow-up to rate the severity and impact of fatigue they experienced in the preceding 2 weeks on their daily lives. FSS total scores are the average of nine questions with a range from 1 [no fatigue] to 7 [worst possible fatigue]. An area under the curve (AUC) analysis compared the overall severity of fatigue in each treatment group from baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in the amount of fatigue participants experienced throughout the study resulting in equal AUC from baseline to Week 72 (AUC72) for FSS total scores. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) and the statistical comparison between treatment groups.
Time Frame	Baseline to Week 60 and Week 72

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	260	130
Week 60	214.907	235.586
Week 72	250.522	274.322

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	Fatigue Severity Score AUC60
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Piecewise-Linear Model Approach
	Comments
Method of Estimation	Estimation Parameter	Mean differences
	Estimated Value	-20.679
	Confidence Interval	(2-Sided) 95%; -32.6399 to -8.7181
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.0979
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	Fatigue Severity Score AUC72
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Piecewise Linear Model
	Comments
Method of Estimation	Estimation Parameter	Mean differences
	Estimated Value	-23.800
	Confidence Interval	(2-Sided) 95%; -37.9931 to -9.6064
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 7.2358
	Estimation Comments

32. Secondary Outcome

Title	Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Overall Work Productivity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Description	Impairment in overall work productivity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire completed by participants during study visits throughout the study. WPAI Overall Productivity Scores ranged from 0% to 100% (higher WPAI scores indicated greater impairment in productivity). An area under the curve (AUC) analysis compared the overall WPAI Overall Work Productivity Scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in the WPAI Overall Work Productivity Scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in WPAI Work Productivity Scores and the statistical comparison between treatment groups.
Time Frame	Baseline to Week 60 and Week 72

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	260	130
Week 60	1555.204	1785.668
Week 72	1718.241	1966.449

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	Impairment in Work Productivity AUC60
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.030
	Comments
	Method	Piecewise Linear Model
	Comments
Method of Estimation	Estimation Parameter	Mean differences
	Estimated Value	-230.464
	Confidence Interval	(2-Sided) 95%; -438.2662 to -22.6626
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 105.9203
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	Impairment in Work Productivity AUC72
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	Piecewise Linear Model
	Comments
Method of Estimation	Estimation Parameter	Mean differences
	Estimated Value	-248.208
	Confidence Interval	(2-Sided) 95%; -492.8253 to -3.5916
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 124.6753
	Estimation Comments

33. Secondary Outcome

Title	Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) for Impairment in Daily Activity Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Description	Impairment in daily activity was measured using the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire, Question 6. Scores ranged from 0 (no effect on activities) to 10 (completely prevented me from doing my daily activities). An area under the curve (AUC) analysis compared the impairment in daily activity scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms in impairment in daily activity scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in the impairment in daily activity scores and the statistical comparison between treatment groups.
Time Frame	Baseline to Week 60 and Week 72

Outcome Measure Data

Analysis Population Description

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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	260	130
Week 60	1514.400	1792.460
Week 72	1667.735	1975.457

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	Impairment in Daily Activities AUC60
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Piecewise linear model
	Comments
Method of Estimation	Estimation Parameter	Mean Differences
	Estimated Value	-278.060
	Confidence Interval	(2-Sided) 95%; -485.2529 to -70.8668
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 105.6088
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	Impairment in Daily Activities AUC72
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Piecewise Linear Model
	Comments
Method of Estimation	Estimation Parameter	Mean differences
	Estimated Value	-307.722
	Confidence Interval	(2-Sided) 95%; -551.4006 to -64.0429
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 124.1956
	Estimation Comments

34. Secondary Outcome

Title	Area Under the Curve From Baseline to Week 60 (AUC60) and Week 72 (AUC72) in Work Productivity and Activity (WPAI) Absenteeism Scores Due to Hepatitis C Virus (HCV) Infection and Its Treatment
Description	Time missed from work in hours because of HCV infection or its treatment was assessed by measuring the change from baseline in the Work Productivity and Activity Impairment (WPAI): Hepatitis C questionnaire Absenteeism score (time missed from work, question #2). The number of hours missed from work because of HCV was divided by the total number of hours supposed to work, and expressed as a percentage. An area under the curve (AUC) analysis compared the WPAI absenteeism scores in each treatment group from Baseline to Week 72. The null hypothesis was that there would be no difference between the treatment arms WPAI absenteeism scores from Baseline to Week 72. The Table below shows the lease squares (LS) mean estimates of AUC at Week 72 (as well as at Week 60) in WPAI absenteeism scores and the statistical comparison between treatment groups.
Time Frame	Baseline to Week 60 and Week 72

Outcome Measure Data

Analysis Population Description

Analysis Population Description: 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/Group Title	TMC435 150mg 12Wks PR24/48	PBO 12Wks PR48
Arm/Group Description	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).	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).
Measure Participants	167	80
Week 60	447.170	400.771
Week 72	487.449	430.285

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	Time Missed from Work AUC60
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.642
	Comments
	Method	Piecewise linear model
	Comments
Method of Estimation	Estimation Parameter	Mean differences
	Estimated Value	46.399
	Confidence Interval	(2-Sided) 95%; -149.6374 to 242.4360
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 99.7966
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMC435 150mg 12Wks PR24/48, PBO 12Wks PR48
	Comments	Time Missed from Work AUC72
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.620
	Comments
	Method	Piecewise Linear Model
	Comments
Method of Estimation	Estimation Parameter	Mean differences
	Estimated Value	57.164
	Confidence Interval	(2-Sided) 95%; -169.1143 to 283.4414
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 115.1548
	Estimation Comments

Adverse Events

Time Frame	72 weeks
Arm/Group Title	TMC435 150mg 12Wks PR24/48		PBO 12Wks PR48
Arm/Group Description	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).		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).
All Cause Mortality
	TMC435 150mg 12Wks PR24/48		PBO 12Wks PR48
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	TMC435 150mg 12Wks PR24/48		PBO 12Wks PR48
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/264 (3.8%)		8/130 (6.2%)
Blood and lymphatic system disorders
Anaemia	0/264 (0%)		1/130 (0.8%)
Cardiac disorders
Palpitations	1/264 (0.4%)		0/130 (0%)
Acute myocardial infarction	0/264 (0%)		1/130 (0.8%)
Myocardial infarction	0/264 (0%)		1/130 (0.8%)
Endocrine disorders
Goitre	0/264 (0%)		1/130 (0.8%)
Gastrointestinal disorders
Vomiting	1/264 (0.4%)		0/130 (0%)
Hepatobiliary disorders
Bile duct obstruction	1/264 (0.4%)		0/130 (0%)
Hepatic lesion	1/264 (0.4%)		0/130 (0%)
Infections and infestations
Abscess limb	1/264 (0.4%)		0/130 (0%)
Cellulitis	1/264 (0.4%)		0/130 (0%)
Lower respiratory tract infection	1/264 (0.4%)		0/130 (0%)
Pneumonia	1/264 (0.4%)		0/130 (0%)
Staphylococcal infection	0/264 (0%)		1/130 (0.8%)
Injury, poisoning and procedural complications
Overdose	1/264 (0.4%)		0/130 (0%)
Rib fracture	1/264 (0.4%)		0/130 (0%)
Metabolism and nutrition disorders
Hyponatraemia	1/264 (0.4%)		0/130 (0%)
Nervous system disorders
Syncope	3/264 (1.1%)		0/130 (0%)
Migraine	0/264 (0%)		1/130 (0.8%)
Psychiatric disorders
Depression	2/264 (0.8%)		0/130 (0%)
Major depression	1/264 (0.4%)		0/130 (0%)
Suicidal ideation	1/264 (0.4%)		0/130 (0%)
Anxiety	0/264 (0%)		1/130 (0.8%)
Renal and urinary disorders
Acute prerenal failure	1/264 (0.4%)		0/130 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/264 (0.4%)		0/130 (0%)
Vascular disorders
Hypotension	1/264 (0.4%)		0/130 (0%)
Aortic stenosis	0/264 (0%)		1/130 (0.8%)
Arterial stenosis limb	0/264 (0%)		1/130 (0.8%)
Other (Not Including Serious) Adverse Events
	TMC435 150mg 12Wks PR24/48		PBO 12Wks PR48
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	252/264 (95.5%)		124/130 (95.4%)
Blood and lymphatic system disorders
Neutropenia	54/264 (20.5%)		15/130 (11.5%)
Anaemia	44/264 (16.7%)		24/130 (18.5%)
Thrombocytopenia	18/264 (6.8%)		5/130 (3.8%)
Gastrointestinal disorders
Nausea	65/264 (24.6%)		32/130 (24.6%)
Diarrhoea	35/264 (13.3%)		19/130 (14.6%)
Vomiting	23/264 (8.7%)		9/130 (6.9%)
Abdominal pain upper	17/264 (6.4%)		9/130 (6.9%)
Constipation	16/264 (6.1%)		4/130 (3.1%)
Dyspepsia	14/264 (5.3%)		5/130 (3.8%)
General disorders
Fatigue	111/264 (42%)		53/130 (40.8%)
Influenza like illness	62/264 (23.5%)		26/130 (20%)
Pyrexia	51/264 (19.3%)		28/130 (21.5%)
Chills	33/264 (12.5%)		18/130 (13.8%)
Asthenia	25/264 (9.5%)		21/130 (16.2%)
Pain	12/264 (4.5%)		9/130 (6.9%)
Hepatobiliary disorders
Hyperbilirubinaemia	14/264 (5.3%)		4/130 (3.1%)
Infections and infestations
Upper respiratory tract infection	8/264 (3%)		7/130 (5.4%)
Investigations
Neutrophil count decreased	10/264 (3.8%)		8/130 (6.2%)
Alanine aminotransferase increased	3/264 (1.1%)		9/130 (6.9%)
Aspartate aminotransferase increased	3/264 (1.1%)		7/130 (5.4%)
Blood thyroid stimulating hormone increased	1/264 (0.4%)		7/130 (5.4%)
Metabolism and nutrition disorders
Decreased appetite	47/264 (17.8%)		19/130 (14.6%)
Musculoskeletal and connective tissue disorders
Myalgia	39/264 (14.8%)		18/130 (13.8%)
Arthralgia	34/264 (12.9%)		21/130 (16.2%)
Back pain	21/264 (8%)		10/130 (7.7%)
Nervous system disorders
Headache	88/264 (33.3%)		51/130 (39.2%)
Dizziness	23/264 (8.7%)		9/130 (6.9%)
Dysgeusia	16/264 (6.1%)		4/130 (3.1%)
Psychiatric disorders
Insomnia	56/264 (21.2%)		31/130 (23.8%)
Mood altered	39/264 (14.8%)		19/130 (14.6%)
Depression	23/264 (8.7%)		16/130 (12.3%)
Anxiety	16/264 (6.1%)		10/130 (7.7%)
Depressed mood	13/264 (4.9%)		11/130 (8.5%)
Sleep disorder	10/264 (3.8%)		7/130 (5.4%)
Respiratory, thoracic and mediastinal disorders
Cough	25/264 (9.5%)		20/130 (15.4%)
Dyspnoea	23/264 (8.7%)		9/130 (6.9%)
Dyspnoea exertional	17/264 (6.4%)		1/130 (0.8%)
Oropharyngeal pain	16/264 (6.1%)		5/130 (3.8%)
Rhinorrhoea	2/264 (0.8%)		7/130 (5.4%)
Skin and subcutaneous tissue disorders
Pruritus	68/264 (25.8%)		20/130 (15.4%)
Rash	60/264 (22.7%)		30/130 (23.1%)
Dry skin	33/264 (12.5%)		11/130 (8.5%)
Alopecia	30/264 (11.4%)		16/130 (12.3%)
Erythema	15/264 (5.7%)		3/130 (2.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.