PROMISE: An Efficacy, Safety and Tolerability Study of TMC435 in Genotype 1 Hepatitis C-infected Patients Who Relapsed After Previous Therapy

• Sponsor: Janssen R&D Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01281839
• Collaborator: (none)
• Enrollment: 394
• Locations: 71
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effectiveness and safety of TMC435 compared with placebo in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients will also receive peginterferon alfa-2a and ribavirin as part of their treatment.

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

Detailed Description

This is a randomized, double-blind (neither physician nor patients knows the name of the assigned drug), placebo-controlled study of TMC435 in patients who are infected with genotype 1 hepatitis C virus who relapsed after previous interferon-based therapy. Patients in this study will also receive two other drugs for their infection called peginterferon alfa-2a and ribavirin. The purpose of the study is to investigate if TMC435 is superior to placebo in reducing hepatitis C virus to an undetectable level 24 weeks after the end of treatment. For the first 12 weeks, patients will take TMC435 or placebo, plus peginterferon alfa-2a and ribavirin. For the next 12 weeks, patients will take peginterferon alfa-2a and ribavirin only. After that, some patients will continue to take peginterferon alfa-2a and ribavirin for up to 24 additional weeks. Other patients will stop taking peginterferon alfa-2a and ribavirin. The study doctor will inform each patient about how to take their study medication and when they should stop taking it. After a patient stops taking study medication, they will continue to come to the doctor's office for study visits until a total of 72 weeks after they enroll in the study. The total duration of the study is 78 weeks (including screening). Patients will be monitored for safety throughout the study. Study assessments at each study visit may include but are not limited to: blood and urine collection for testing, ECG assessments (a measurement of the electrical activity of your heart), patient questionnaires, and physical examinations TMC435 will be taken as an oral capsule of 150 mg once per day. Peginterferon (Pegasys ®) will be given as an injection of 180 µg once each week. Ribavirin (Copegus ®) will be taken as a tablet twice each day and the dose will depend on your body weight.

Study Design

• Study Type: Interventional
• Actual Enrollment: 394 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 Hepatitis C, Genotype 1 Infected Subjects Who Relapsed After Previous Interferon-based Therapy
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Feb 1, 2013
• Actual Study Completion Date: Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TMC435 TMC435 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin for 24 or 48 weeks	Drug: TMC435; 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin 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 peginterferon alfa-2a and ribavirin for 48 weeks	Drug: Placebo; 150 mg capsule once daily for 12 weeks in addition to peginterferon alfa-2a and ribavirin 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 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. From Week 4 onwards, most participants in TMC 435 150mg 12Wks PR24/48 group had plasma HCV RNA levels below the limit of detection of the HCV RNA assay.

6. The Percentage of Participants With On-treatment Virologic Response at All Time Points [Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42]

   The table below shows the percentage of participants with HCV ribonucleic acid (RNA plasma levels below the limit of detection (ie, <25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA <100 IU/mL, the percentage of participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA.

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 Week 12]

    The table below shows the percentage of participants in each treatment group who had a eRVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 4 and 12.

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. The Percentage of Participants With Null Response [Week 12]

    The table below shows the percentage of participants with null response, defined as <2 log10 reduction in Hepatitis C virus ribonucleic acid at Week 12 compared to baseline.

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

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

15. The Percentage of Participants With Viral Breakthrough [Up to Week 48]

    The table below shows the percentage of participants with viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached (ie, lowest value measured in between baseline and current value), or a confirmed plasma HCV RNA level of greater than 100 IU/mL in participants whose plasma HCV RNA had previously been below the limit of quantification (25 IU/mL detectable) or undetectable (<25 IU/mL undetectable).

16. The Percentage of Participants With Viral Relapse [Up to Week 72]

    The table below shows the percentage of participants with viral relapse, defined as having confirmed detectable plasma level of Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.

17. The Percentage of Participants Who Completed All Study Treatment at Week 24 Because of the Treatment Duration Rule [Week 24]

    The table below shows the percentage of participants in the TMC435 treatment group who met the treatment duration rule (ie, having hepatitis C virus [HCV] ribonucleic acid [RNA] levels <25 IU/mL detectable or undetectable at Week 4 and undetectable HCV RNA levels at Week 12) and completed treatment with PegIFNα-2a and RBV for 24 weeks. Participants in the TMC435 treatment group not meeting RGT criteria and participants in the placebo group were treated with PegIFNα-2a and RBV treatment for 48 weeks.

18. The Percentage of Participants With On-treatment Failure [Week 48]

    The table below shows percentage of participants with on-treatment failure defined as confirmed detectable Hepatitis C virus ribonucleic acid levels at actual end of treatment.

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

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

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

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

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

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

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

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

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, 156 of 260 participants in the TMC435 treatment group and 84 of 133 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range.

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

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

27. Plasma Concentration of TMC435: Area Under the Plasma Concentration-time Curve From the Time of Administration to 24 Hours After Dosing (AUC24h) [From the time of administration up to 24 hours after dosing through Week 12]

    The table below shows mean (standard deviation) values of the area under the plasma concentration-time curve from time of administration to 24 hours (AUC 24hr) after dosing for TMC435. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then the median of AUC value across visits for each participant was used to calculate the mean AUC 24 hr for the study.

28. Plasma Concentration of TMC435: Predose Plasma Concentration (C0h) [Before administration of TMC435 through Week 12]

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

29. Plasma Concentration of TMC435: Systemic Clearance (CL) [From the time of administration through Week 12]

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

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)

• Have previously received peginterferon-based therapy for at least 24 weeks with documented HCV RNA at last measurement and relapsed within 1 year of last taking medication

• Liver biopsy within 3 years before screening (or between the screening and baseline visit) showing chronic hepatitis C infection

• Must agree to use 2 forms of effective contraception throughout study (both males and females)

Exclusion Criteria:

• Infection with HIV or non-genotype 1 hepatitis C

• Liver disease not related to hepatitic C infection

• Hepatic decompensation

• Significant laboratory abnormalities or other active diseases

• Pregnant or planning to become pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bakersfield	California	United States
2		Aurora	Colorado	United States
3		Jacksonville	Florida	United States
4		Orlando	Florida	United States
5		Atlanta	Georgia	United States
6		Crestview Hills	Kentucky	United States
7		Saint Paul	Minnesota	United States
8		Jackson	Mississippi	United States
9		Germantown	Tennessee	United States
10		Houston	Texas	United States
11		San Antonio	Texas	United States
12		Adelaide		Australia
13		Kingswood		Australia
14		Melbourne		Australia
15		Sydney		Australia
16		Woolloongabba N/A		Australia
17		Wien		Austria
18		Antwerpen		Belgium
19		Brugge		Belgium
20		Brussels		Belgium
21		Brussel		Belgium
22		Gent		Belgium
23		Leuven		Belgium
24		Vancouver	British Columbia	Canada
25		Ottawa	Ontario	Canada
26		Toronto	Ontario	Canada
27		Montreal	Quebec	Canada
28		Creteil N/A		France
29		Grenoble		France
30		Lyon		France
31		Nice N/A		France
32		Paris Cedex 12		France
33		Paris		France
34		Rennes Cedex		France
35		Vandoeuvre Les Nancy		France
36		Berlin		Germany
37		Düsseldorf		Germany
38		Frankfurt		Germany
39		Freiburg		Germany
40		Halle (Saale)		Germany
41		Hamburg		Germany
42		Kiel		Germany
43		Leipzig		Germany
44		Munchen		Germany
45		Würzburg		Germany
46		Auckland		New Zealand
47		Christchurch		New Zealand
48		Hamilton		New Zealand
49		Bialystok		Poland
50		Bydgoszcz		Poland
51		Czeladz		Poland
52		Kielce		Poland
53		Krakow		Poland
54		Warszawa		Poland
55		Ponce Pr		Puerto Rico
56		San Juan		Puerto Rico
57		Moscow		Russian Federation
58		Saint-Petersburg		Russian Federation
59		Samara		Russian Federation
60		Smolensk		Russian Federation
61		St Petersburg		Russian Federation
62		Stavropol		Russian Federation
63		Barcelona		Spain
64		Madrid		Spain
65		Sevilla N/A		Spain
66		Valencia		Spain
67		Birmingham		United Kingdom
68		Derby		United Kingdom
69		Glasgow		United Kingdom
70		London		United Kingdom
71		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: NCT01281839
• Other Study ID Numbers: CR017371; TMC435HPC3007; 2010-021113-23
• First Posted: Jan 24, 2011
• Last Update Posted: Apr 23, 2014
• Last Verified: Mar 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 4 February 2013. The study was conducted at 81 sites in 14 countries.
Pre-assignment Detail	394 participants were randomly allocated to the 2 treatment arms. 393 participants received at least 1 dose of study medication and were included in the intent-to-treat analysis set.

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	260	133
COMPLETED	250	119
NOT COMPLETED	10	14

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	260	133	393
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52	52	52
Sex: Female, Male (Count of Participants)
Female	81 31.2%	54 40.6%	135 34.4%
Male	179 68.8%	79 59.4%	258 65.6%

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	260	133
Number [Percentage of participants]	79.2 30.5%	36.1 27.1%

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	43.8
	Confidence Interval	(2-Sided) 95%; 34.6 to 53.0
	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	260	133
Number [Percentage of Participants]	76.5 29.4%	33.8 25.4%

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 SVR72 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 SVR72
	Estimated Value	43.3
	Confidence Interval	(2-Sided) 95%; 34.1 to 52.5
	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	260	133
Number [Percentage of Participants]	77.3 29.7%	33.8 25.4%

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	44.1
	Confidence Interval	(2-Sided) 95%; 34.9 to 53.2
	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	260	133
Number [Percentage of Participants]	88.5 34%	48.1 36.2%

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 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 SVR4
	Estimated Value	41.0
	Confidence Interval	(2-Sided) 95%; 32.1 to 49.9
	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 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	260	133
Day 3	-3.537 (0.042)	-1.039 (0.072)
Week 1	-4.535 (0.040)	-1.099 (0.073)
Week 4	-5.295 (0.049)	-2.638 (0.125)
Week 12	-5.404 (0.049)	-4.476 (0.113)
Week 24	-5.449 (0.036)	-5.373 (0.070)
Week 48	-5.635 (0.212)	-5.473 (0.068)

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. From Week 4 onwards, most participants in TMC 435 150mg 12Wks PR24/48 group had plasma HCV RNA levels below the limit of detection of the HCV RNA assay.
Time Frame	Day 3, Week 1, Week 4, Week 12, Week 24, and Week 48

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	133
Day 3	2.884 (0.049)	5.445 (0.084)
Week 1	1.889 (0.041)	5.376 (0.084)
Week 4	1.128 (0.034)	3.838 (0.130)
Week 12	1.018 (0.034)	2.005 (0.109)
Week 24	0.956 (0.002)	1.108 (0.042)
Week 48	0.954 (0.000)	0.995 (0.013)

7. Secondary Outcome

Title	The Percentage of Participants With On-treatment Virologic Response at All Time Points
Description	The table below shows the percentage of participants with HCV ribonucleic acid (RNA plasma levels below the limit of detection (ie, <25 IU/mL undetectable), the percentage of participants with a HCV RNA plasma level below the limit of quantification (ie, less than [<] 25 IU/mL detectable or undetectable), the percentage of participants with plasma levels of HCV RNA <100 IU/mL, the percentage of participants with virologic responses of a greater than or equal to 2 log10 change from baseline in plasma levels of HCV RNA.
Time Frame	Day 3, Week 1, Week 2, Week 8, Week 16, Week 20, Week 28, Week 36, and Week 42

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	133
Day 3:<25 IU/mL undetectable	0 0%	0.8 0.6%
Week 1:<25 IU/mL undetectable	3.9 1.5%	0 0%
Week 2:<25 IU/mL undetectable	28.3 10.9%	0.8 0.6%
Week 8:<25 IU/mL undetectable	95.7 36.8%	15.0 11.3%
Week 16:<25 IU/mL	98.4 37.8%	47.4 35.6%
Week 20:<25 IU/mL	99.6 38.3%	65.5 49.2%
Week 28:<25 IU/mL	88.9 34.2%	84.5 63.5%
Week 36:<25 IU/mL	90.0 34.6%	91.9 69.1%
Week 42:<25 IU/mL	100.0 38.5%	91.7 68.9%
Day 3:<25 IU/mL undetectable/detectable	3.1 1.2%	0.8 0.6%
Week 1:<25 IU/mL undetectable/detectable	35.9 13.8%	0.8 0.6%
Week 2:<25 IU/mL undetectable/detectable	82.6 31.8%	1.5 1.1%
Week 8:<25 IU/mL undetectable/detectable	98.0 37.7%	27.6 20.8%
Week 16:<25 IU/mL undetectable/detectable	100.0 38.5%	77.6 58.3%
Week 20:<25 IU/mL undetectable/detectable	99.6 38.3%	89.4 67.2%
Week 28:<25 IU/mL undetectable/detectable	100.0 38.5%	100.0 75.2%
Week 36:<25 IU/mL undetectable/detectable	90.0 34.6%	99.0 74.4%
Week 42:<25 IU/mL undetectable/detectable	100.0 38.5%	97.9 73.6%
Day 3:<100 IU/mL	9.1 3.5%	0.8 0.6%
Week 1:<100 IU/mL	62.2 23.9%	0.8 0.6%
Week 2:<100 IU/mL	92.2 35.5%	2.3 1.7%
Week 8:<100 IU/mL	98.0 37.7%	37.0 27.8%
Week 16:<100 IU/mL	100.0 38.5%	84.5 63.5%
Week 20:<100 IU/mL	99.6 38.3%	93.8 70.5%
Week 28:<100 IU/mL	100.0 38.5%	100.0 75.2%
Week 36:<100 IU/mL	90.0 34.6%	100.0 75.2%
Week 42:<100 IU/mL	100.0 38.5%	100.0 75.2%
Day 3:> or = 2 log10 change from baseline	97.6 37.5%	14.1 10.6%
Week 1:> or = 2 log10 change from baseline	99.6 38.3%	13.7 10.3%
Week 2:> or = 2 log10 change from baseline	99.6 38.3%	35.4 26.6%
Week 8:> or = 2 log10 change from baseline	98.4 37.8%	87.4 65.7%
Week 16:> or = 2 log10 change from baseline	100.0 38.5%	100.0 75.2%
Week 20:> or = 2 log10 change from baseline	100.0 38.5%	100.0 75.2%
Week 28:> or = 2 log10 change from baseline	100.0 38.5%	100.0 75.2%
Week 36:> or = 2 log10 change from baseline	100.0 38.5%	100.0 75.2%
Week 42:> or = 2 log10 change from baseline	100.0 38.5%	100.0 75.2%

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	260	133
Number [Percentage of Participants]	77.2 29.7%	3.1 2.3%

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	260	133
Number [Percentage of Participants]	98.8 38%	95.2 71.6%

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	260	133
Number [Percentage of Participants]	98.0 37.7%	27.4 20.6%

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 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	260	133
Number [Percentage of Participants]	77.6 29.8%	1.6 1.2%

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	260	133
Number [Percentage of Participants]	0.8 0.3%	9.3 7%

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	260	133
Number [Percentage of Participants]	1.9 0.7%	69.9 52.6%

14. Secondary Outcome

Title	The 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	260	133
Number [Percentage of Participants]	1.2 0.5%	4.8 3.6%

15. Secondary Outcome

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

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	133
Number [Percentage of Participants]	10.5 4%	0 0%

16. Secondary Outcome

Title	The 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	260	133
Number [Percentage of Participants]	0.0 0%	2.3 1.7%

17. Secondary Outcome

Title	The 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	260	133
Number [Percentage of Participants]	18.9 7.3%	50.5 38%

18. Secondary Outcome

Title	The 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	260	133
Number [Percentage of Participants]	90.0 34.6%	0 0%

19. Secondary Outcome

Title	The 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	260	133
Number [Percentage of Participants]	3.1 1.2%	27.1 20.4%

20. Secondary Outcome

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

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	133
Median (95% Confidence Interval) [Days]	28	141

21. Secondary Outcome

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

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	133
Median (95% Confidence Interval) [Days]	14	110

22. Secondary Outcome

Title	Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <100 IU/mL
Description	The table below shows mean 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	260	133
Median (95% Confidence Interval) [Days]	8	85

23. Secondary Outcome

Title	Time to Reach Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <1000 IU/mL
Description	The table below shows mean 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	260	133
Median (95% Confidence Interval) [Days]	4	57

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	260	133
=<12 weeks	1.9 0.7%	0.0 0%
>12-=<24 weeks	0.0 0%	0.0 0%
>24 weeks	10.0 3.8%	0.0 0%

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	260	133
Mean (Standard Error) [Days]	284.09 (6.56)	115.22 (6.72)

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, 156 of 260 participants in the TMC435 treatment group and 84 of 133 participants in the Placebo group had ALT values at baseline that were out of the normal range.). Normalization of ALT values means that ALT values out of the normal range returned to within the normal range.
Time Frame	Up to Week 48

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	156	84
Number [Percentage of Participants]	69.9 26.9%	69.0 51.9%

27. Secondary Outcome

Title	Median Time to Normalization of Alanine Aminotransferase (ALT) Levels
Description	The table below shows the median time 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	260	133
Median (95% Confidence Interval) [Weeks]	7.86	8.00

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 (AUC 24hr) after dosing for TMC435. To calculate the mean AUC 24 for the study, AUC 24 hr values were derived for each participant at each visit and then the median of AUC value across visits for each participant was used to calculate the mean AUC 24 hr for the study.
Time Frame	From the time of administration up to 24 hours after dosing through Week 12

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]	60987 (67577.4)

29. Secondary Outcome

Title	Plasma Concentration of TMC435: Predose Plasma Concentration (C0h)
Description	The table below shows mean (standard deviation) of C0h values of TMC435. To calculate the mean C0h for the study, C0h values were derived for each participant at each visit and then the median of C0h values across visits for each participant was used to calculate the mean C0h for the study.
Time Frame	Before administration of TMC435 through Week 12

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]	2081 (2807.6)

30. Secondary Outcome

Title	Plasma Concentration of TMC435: Systemic Clearance (CL)
Description	The table below shows mean (standard deviation) of CL values of TMC435. To calculate the mean CL for the study, CL values were derived for each participant at each visit and then the median of CL values across visits for each participant was used to calculate the mean CL for the study.
Time Frame	From the time of administration through Week 12

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]	4.92 (3.438)

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	14/260 (5.4%)		11/133 (8.3%)
Blood and lymphatic system disorders
Anaemia haemolytic autoimmune	1/260 (0.4%)		0/133 (0%)
Pancytopenia	1/260 (0.4%)		0/133 (0%)
Cardiac disorders
Angina pectoris	1/260 (0.4%)		0/133 (0%)
Bradycardia	1/260 (0.4%)		0/133 (0%)
Myocardial ischaemia	1/260 (0.4%)		0/133 (0%)
Atrial fibrillation	0/260 (0%)		1/133 (0.8%)
Pericarditis	0/260 (0%)		1/133 (0.8%)
Gastrointestinal disorders
Abdominal pain	1/260 (0.4%)		0/133 (0%)
Inguinal hernia	0/260 (0%)		1/133 (0.8%)
General disorders
Pyrexia	1/260 (0.4%)		0/133 (0%)
Hepatobiliary disorders
Cholelithiasis	1/260 (0.4%)		0/133 (0%)
Hepatitis	1/260 (0.4%)		0/133 (0%)
Infections and infestations
Pneumonia	2/260 (0.8%)		0/133 (0%)
Appendicitis	1/260 (0.4%)		0/133 (0%)
Endocarditis	1/260 (0.4%)		0/133 (0%)
Lower respiratory tract infection	1/260 (0.4%)		0/133 (0%)
Septic shock	1/260 (0.4%)		0/133 (0%)
Arthritis infective	0/260 (0%)		1/133 (0.8%)
Bacterial prostatitis	0/260 (0%)		1/133 (0.8%)
Bronchitis	0/260 (0%)		1/133 (0.8%)
Infection	0/260 (0%)		1/133 (0.8%)
Injury, poisoning and procedural complications
Head injury	0/260 (0%)		1/133 (0.8%)
Metabolism and nutrition disorders
Hypercalcaemia	0/260 (0%)		1/133 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/260 (0.4%)		0/133 (0%)
Nervous system disorders
Guillain-Barre syndrome	1/260 (0.4%)		0/133 (0%)
Presyncope	1/260 (0.4%)		0/133 (0%)
Headache	0/260 (0%)		1/133 (0.8%)
Neuropathy peripheral	0/260 (0%)		1/133 (0.8%)
Psychiatric disorders
Confusional state	1/260 (0.4%)		0/133 (0%)
Depression	1/260 (0.4%)		1/133 (0.8%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/260 (0.4%)		0/133 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/260 (0.4%)		0/133 (0%)
Dyspnoea	1/260 (0.4%)		0/133 (0%)
Respiratory acidosis	1/260 (0.4%)		0/133 (0%)
Skin and subcutaneous tissue disorders
Photosensitivity reaction	2/260 (0.8%)		0/133 (0%)
Other (Not Including Serious) Adverse Events
	TMC435 150mg 12Wks PR24/48		PBO 12Wks PR48
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	245/260 (94.2%)		123/133 (92.5%)
Blood and lymphatic system disorders
Anaemia	40/260 (15.4%)		24/133 (18%)
Neutropenia	37/260 (14.2%)		26/133 (19.5%)
Gastrointestinal disorders
Nausea	59/260 (22.7%)		26/133 (19.5%)
Diarrhoea	36/260 (13.8%)		22/133 (16.5%)
Vomiting	18/260 (6.9%)		9/133 (6.8%)
Abdominal pain upper	10/260 (3.8%)		9/133 (6.8%)
Abdominal pain	9/260 (3.5%)		8/133 (6%)
General disorders
Fatigue	87/260 (33.5%)		58/133 (43.6%)
Influenza like illness	78/260 (30%)		27/133 (20.3%)
Pyrexia	63/260 (24.2%)		30/133 (22.6%)
Asthenia	57/260 (21.9%)		25/133 (18.8%)
Injection site erythema	21/260 (8.1%)		9/133 (6.8%)
Chills	17/260 (6.5%)		11/133 (8.3%)
Infections and infestations
Nasopharyngitis	5/260 (1.9%)		7/133 (5.3%)
Metabolism and nutrition disorders
Decreased appetite	35/260 (13.5%)		24/133 (18%)
Musculoskeletal and connective tissue disorders
Myalgia	39/260 (15%)		17/133 (12.8%)
Arthralgia	26/260 (10%)		12/133 (9%)
Back pain	15/260 (5.8%)		8/133 (6%)
Nervous system disorders
Headache	87/260 (33.5%)		48/133 (36.1%)
Dizziness	14/260 (5.4%)		6/133 (4.5%)
Dysgeusia	12/260 (4.6%)		7/133 (5.3%)
Disturbance in attention	10/260 (3.8%)		7/133 (5.3%)
Psychiatric disorders
Insomnia	49/260 (18.8%)		33/133 (24.8%)
Mood altered	25/260 (9.6%)		22/133 (16.5%)
Depression	22/260 (8.5%)		10/133 (7.5%)
Sleep disorder	15/260 (5.8%)		14/133 (10.5%)
Depressed mood	10/260 (3.8%)		8/133 (6%)
Respiratory, thoracic and mediastinal disorders
Cough	34/260 (13.1%)		21/133 (15.8%)
Dyspnoea	26/260 (10%)		5/133 (3.8%)
Dyspnoea exertional	16/260 (6.2%)		8/133 (6%)
Skin and subcutaneous tissue disorders
Pruritus	72/260 (27.7%)		37/133 (27.8%)
Rash	33/260 (12.7%)		19/133 (14.3%)
Alopecia	26/260 (10%)		17/133 (12.8%)
Dry skin	24/260 (9.2%)		18/133 (13.5%)
Eczema	14/260 (5.4%)		4/133 (3%)
Erythema	7/260 (2.7%)		7/133 (5.3%)

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.