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

• Sponsor: Tibotec Pharmaceuticals, Ireland (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00882908
• Collaborator: (none)
• Enrollment: 386
• Locations: 73
• Arms: 5
• Duration (Months): 22
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of 4 different regimens of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), defined as the proportion of patients with sustained virologic response at Week 72 (patients with undetectable plasma HCV RNA [less than 25 IU per mL undetectable] at the end of treatment and at Week 72), compared to the control group receiving PegIFN and RBV in combination with TMC435-matched placebo.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: TMC435; Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo	Phase 2

Detailed Description

This is a randomized (study medication assigned by chance), 5-arm, double-blind (neither investigator nor the participant knows the treatment that the participant receives), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study) study to compare the efficacy, tolerability and safety of different TMC435 regimens combined with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) versus PegIFNα-2a plus RBV alone in adult treatment-naive patients with chronic genotype 1 HCV infection. The study mainly consists of 3 phases: screening phase (approximately 6 weeks), treatment phase (up to 48 weeks), and follow up phase (up to 48 weeks). In the treatment phase, patients will be divided in to 5 different arms in a 1:1:1:1:1 randomized ratio. In treatment arms 1 and 2, patients will receive 12 weeks of therapy with TMC435 along with PegIFNα 2a and RBV followed by treatment with PegIFNα 2a, RBV, and TMC435-matched placebo. In treatment arms 3 and 4, patients will receive 24 weeks of therapy with TMC435, PegIFNα 2a, and RBV. In treatment arm 5 (control group), patients will receive PegIFNα 2a and RBV for 48 weeks and TMC435 matched placebo for the first 24 weeks. Collection of blood samples for efficacy evaluations will be done at scheduled visits throughout the study. Safety evaluations for adverse events, clinical laboratory tests, physical examination, vital signs and electrocardiogram will be monitored throughout the study. The total duration of the study will be up to approximately 72 weeks after initiation of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 386 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin In Treatment-Naive Genotype 1 Hepatitis C-Infected Subjects
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TMC435 75 mg 12 Wks + PR 24/48 Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Drug: TMC435; TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.; Other Names: TMC 435 ; Drug: Ribavirin (R); Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.; Other Names: COPEGUS ; Drug: PegIFNα-2a (P); PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.; Other Names: PEGASYS ; Drug: Placebo; Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Experimental: TMC435 75 mg 24 Wks + PR 24/48 Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Drug: TMC435; TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.; Other Names: TMC 435 ; Drug: Ribavirin (R); Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.; Other Names: COPEGUS ; Drug: PegIFNα-2a (P); PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.; Other Names: PEGASYS ; Drug: Placebo; Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Experimental: TMC435 150 mg 12 Wks + PR 24/48 Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Drug: TMC435; TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.; Other Names: TMC 435 ; Drug: Ribavirin (R); Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.; Other Names: COPEGUS ; Drug: PegIFNα-2a (P); PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.; Other Names: PEGASYS ; Drug: Placebo; Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Experimental: TMC435 150 mg 24 Wks + PR 24/48 Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Drug: TMC435; TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.; Other Names: TMC 435 ; Drug: Ribavirin (R); Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.; Other Names: COPEGUS ; Drug: PegIFNα-2a (P); PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.; Other Names: PEGASYS ; Drug: Placebo; Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Placebo Comparator: Placebo 24 Wks + PR48 Participants will receive Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.	Drug: Ribavirin (R); Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.; Other Names: COPEGUS ; Drug: PegIFNα-2a (P); PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.; Other Names: PEGASYS ; Drug: Placebo; Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

Outcome Measures

Primary 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.

Secondary Outcome Measures

1. The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up [Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)]

   The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels of less than 25 IU/mL undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).

2. The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up [Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)]

   The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA less than 25 IU/mL detectable or undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).

3. The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment [Baseline (Day 1) and Weeks, 2, 4, 8, and 12]

   The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA greater than or equal to 2 log10 drop from Baseline at selected time points during treatment.

4. The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24) [Week 48 or 72]

   The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 24 weeks after the EOT.

5. 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.

6. The Percentage of Participants Achieving an Early Virologic Response (EVR) [Baseline (Day 1) and 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 2 log10 at Week 12.

7. 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.

8. The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12) [Up to Week 36 or 52]

   The table below shows the percentage of participants who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the EOT.

9. Number of Participants With Viral Breakthrough [Week 24 or 48]

   The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period of the study, defined as a confirmed increase of more than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA more than 100 IU/mL in participants whose plasma HCV RNA level had previously been below the limit of quantification (less than 25 IU/mL detectable or undetectable).

10. The Number of Participants With Viral Relapse [Up to Week 72]

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

11. The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT) [Baseline (Day 1) up to Week 24 or 48]

    The table below shows the number of participants with abnormal ALT levels at Baseline who achieved ALT levels within the normal range at the EOT.

12. Plasma Concentrations of TMC435 [Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24]

    The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for participants in each of the 4 TMC435 treatment groups.

13. Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435 [Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24]

    The table below shows the median (range) AUC24h values for TMC435 for participants in each of the 4 TMC435 treatment groups. Two blood samples taken at least 2 hours apart from each other for determination of TMC435 plasma pharmacokinetics were obtained in all participants on Weeks 2, 4, 8, 12, 16, and 24 to obtain Bayesian estimates of TMC435 AUC24h (overall exposure).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with documented chronic genotype-1 hepatitis C infection and with plasma HCV RNA of > 100,000 IU/mL at screening

• Patients that have not been treated before for HCV

• Patients that are of childbearing potential or have a partner of childbearing potential should agree to use 2 effective methods of contraception

Exclusion Criteria:

• Patients with cirrhosis or evidence of hepatic decompensation

• Co-infection with the human immunodeficiency virus (HIV)

• Any contraindication to Pegasys or Copegus therapy

• History of, or any current medical condition which could impact the safety of the patient in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States
2		Jacksonville	Florida	United States
3		Orlando	Florida	United States
4		Palm Harbor	Florida	United States
5		Chicago	Illinois	United States
6		New Orleans	Louisiana	United States
7		Saint Paul	Minnesota	United States
8		New York	New York	United States
9		Chapel Hill	North Carolina	United States
10		Cincinnati	Ohio	United States
11		Germantown	Tennessee	United States
12		Charlottesville	Virginia	United States
13		Concord		Australia
14		Darlinghurst		Australia
15		Fitzroy		Australia
16		Melbourne		Australia
17		Sydney		Australia
18		Woolloongabba N/A		Australia
19		Wien		Austria
20		Brugge		Belgium
21		Brussels		Belgium
22		Bruxelles		Belgium
23		Edegem		Belgium
24		Gent		Belgium
25		Leuven		Belgium
26		Roeselare		Belgium
27		Calgary	Alberta	Canada
28		Toronto	Ontario	Canada
29		Montreal	Quebec	Canada
30		Aarhus		Denmark
31		Copenhagen		Denmark
32		Hvidovre N/A		Denmark
33		Kolding		Denmark
34		Odense N/A		Denmark
35		Clichy		France
36		Creteil N/A		France
37		Grenoble		France
38		Lyon		France
39		Nice		France
40		Paris		France
41		Vandoeuvre Les Nancy		France
42		Berlin		Germany
43		Düsseldorf		Germany
44		Frankfurt A. M.		Germany
45		Freiburg		Germany
46		Hamburg		Germany
47		Hannover		Germany
48		Köln		Germany
49		Stuttgart		Germany
50		Würzburg		Germany
51		Auckland		New Zealand
52		Christchurch		New Zealand
53		Hamilton		New Zealand
54		Bergen		Norway
55		Nordbyhagen		Norway
56		Oslo		Norway
57		Tromsø		Norway
58		Bialystok		Poland
59		Bydgoszcz		Poland
60		Czeladz		Poland
61		Kielce		Poland
62		Lodz		Poland
63		Warschau		Poland
64		Moscow		Russian Federation
65		Nizhny Novgorod		Russian Federation
66		Saint-Petersburg		Russian Federation
67		Samara		Russian Federation
68		Smolensk		Russian Federation
69		St Petersburg		Russian Federation
70		Barcelona		Spain
71		Madrid		Spain
72		Sevilla N/A		Spain
73		Valencia		Spain

Sponsors and Collaborators

• Tibotec Pharmaceuticals, Ireland

Investigators

• Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial, Tibotec Pharmaceuticals, Ireland

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tibotec Pharmaceuticals, Ireland
• ClinicalTrials.gov Identifier: NCT00882908
• Other Study ID Numbers: CR015799; TMC435-TiDP16-C205; 2008-007147-13
• First Posted: Apr 17, 2009
• Last Update Posted: Jun 16, 2014
• Last Verified: May 1, 2014

• Keywords provided by Tibotec Pharmaceuticals, Ireland: Hepatitis C; TMC435; Peginterferon alpha-2a; PegIFNalpha-2a; RBV; Ribavirin; Placebo
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis; Ribavirin; Simeprevir

Study Results

Participant Flow

Recruitment Details	The study was conducted at 79 sites in 13 countries: Australia, New Zealand, Canada, Austria, Belgium, Germany, Spain, France, Poland, Russia, Norway, Denmark, and the United States. Approximately 68% of participants were enrolled in Europe, 21% in North America, and 11% in Australia/New Zealand.
Pre-assignment Detail	In total, 506 participants were screened; 388 participants were randomized of whom 386 participants started treatment. Two randomized participants did not start treatment due to withdrawal of consent.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Period Title: Overall Study
STARTED	78	75	77	79	77
COMPLETED	75	69	70	72	71
NOT COMPLETED	3	6	7	7	6

Baseline Characteristics

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48	Total
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.	Total of all reporting groups
Overall Participants	78	75	77	79	77	386
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	47	46	47	47	45	46.5
Sex: Female, Male (Count of Participants)
Female	38 48.7%	28 37.3%	34 44.2%	35 44.3%	38 49.4%	173 44.8%
Male	40 51.3%	47 62.7%	43 55.8%	44 55.7%	39 50.6%	213 55.2%
Region of Enrollment (participants) [Number]
Asia Pacific	9 11.5%	9 12%	7 9.1%	13 16.5%	4 5.2%	42 10.9%
Europe	52 66.7%	52 69.3%	56 72.7%	44 55.7%	58 75.3%	262 67.9%
North-America	17 21.8%	14 18.7%	14 18.2%	22 27.8%	15 19.5%	82 21.2%

Outcome Measures

1. Primary 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 those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Number [Percentage of participants]	80.8 103.6%	70.7 94.3%	77.9 101.2%	84.8 107.3%	64.9 84.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TMC435 75 mg 12 Wks + PR 24/48, TMC435 75 mg 24 Wks + PR 24/48, Placebo 24 Wks + PR48
	Comments	TMC435 75 mg 12 and 24 week treatment groups were pooled and the percentage of participants acheiving SVRW72 were compared with the percentage of participants acheiving SVRW72 in the placebo treatment group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.051
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions of SVRW72
	Estimated Value	13.0
	Confidence Interval	(2-Sided) 97.5%; -1.9 to 28.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentages of participants in the TMC435 75mg and placebo groups with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72 estimated from the logistic regression model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	TMC435 150 mg 12 Wks + PR 24/48, TMC435 150 mg 24 Wks + PR 24/48, Placebo 24 Wks + PR48
	Comments	TMC/PR 150 mg 12 and 24 week treatment groups were pooled and the percentage of participants achieving SVRW72 was compared the percentage of participants achieving SVRW72 in the placebo treatment group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions of SVRW72
	Estimated Value	18.9
	Confidence Interval	(2-Sided) 97.5%; 4.4 to 33.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in percentages of participants in the TMC435 150mg and placebo groups with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72 estimated from the logistic regression model.

2. Secondary Outcome

Title	The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up
Description	The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels of less than 25 IU/mL undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
Time Frame	Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

Outcome Measure Data

Analysis Population Description

The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Week 2	39.7 50.9%	30.7 40.9%	23.4 30.4%	39.2 49.6%	2.6 3.4%
Week 4	75.6 96.9%	68.0 90.7%	75.3 97.8%	74.7 94.6%	5.2 6.8%
Week 8	87.2 111.8%	90.7 120.9%	92.2 119.7%	93.7 118.6%	26.0 33.8%
Week 12	91.0 116.7%	93.3 124.4%	93.5 121.4%	94.9 120.1%	55.8 72.5%
Week 24	92.3 118.3%	93.3 124.4%	84.4 109.6%	87.3 110.5%	77.9 101.2%
Week 36	85.9 110.1%	81.3 108.4%	81.8 106.2%	84.8 107.3%	76.6 99.5%
Week 48	79.5 101.9%	77.3 103.1%	79.2 102.9%	82.3 104.2%	74.0 96.1%
Week 60	79.5 101.9%	68.0 90.7%	75.3 97.8%	83.5 105.7%	63.6 82.6%
Week 72	79.5 101.9%	70.7 94.3%	77.9 101.2%	82.3 104.2%	64.9 84.3%
EOT (up to Week 24 or 48)	92.3 118.3%	97.3 129.7%	92.2 119.7%	93.7 118.6%	79.2 102.9%

3. Secondary Outcome

Title	The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up
Description	The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA less than 25 IU/mL detectable or undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
Time Frame	Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

Outcome Measure Data

Analysis Population Description

The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Week 2	65.4 83.8%	66.7 88.9%	75.3 97.8%	78.5 99.4%	5.2 6.8%
Week 4	85.9 110.1%	88.0 117.3%	90.9 118.1%	91.1 115.3%	15.6 20.3%
Week 8	93.6 120%	94.7 126.3%	93.5 121.4%	93.7 118.6%	49.4 64.2%
Week 12	93.6 120%	94.7 126.3%	96.1 124.8%	94.9 120.1%	66.2 86%
Week 24	92.3 118.3%	93.3 124.4%	84.4 109.6%	89.9 113.8%	80.5 104.5%
Week 36	85.9 110.1%	81.3 108.4%	81.8 106.2%	84.8 107.3%	79.2 102.9%
Week 48	79.5 101.9%	77.3 103.1%	79.2 102.9%	82.3 104.2%	75.3 97.8%
Week 60	79.5 101.9%	68.0 90.7%	75.3 97.8%	83.5 105.7%	64.9 84.3%
Week 72	79.5 101.9%	70.7 94.3%	77.9 101.2%	83.5 105.7%	64.9 84.3%
EOT (up to Week 24 or 48)	93.6 120%	97.3 129.7%	92.2 119.7%	96.2 121.8%	83.1 107.9%

4. Secondary Outcome

Title	The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment
Description	The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA greater than or equal to 2 log10 drop from Baseline at selected time points during treatment.
Time Frame	Baseline (Day 1) and Weeks, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Week 2	93.6 120%	98.7 131.6%	97.4 126.5%	98.7 124.9%	40.3 52.3%
Week 4	94.9 121.7%	98.7 131.6%	97.4 126.5%	93.7 118.6%	71.4 92.7%
Week 8	97.4 124.9%	97.3 129.7%	97.4 126.5%	94.9 120.1%	84.4 109.6%
Week 12	97.4 124.9%	96.0 128%	96.1 124.8%	96.2 121.8%	89.6 116.4%

5. 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 having undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 24 weeks after the EOT.
Time Frame	Week 48 or 72

Outcome Measure Data

Analysis Population Description

The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Number [Percentage of participants]	82.1 105.3%	74.7 99.6%	80.5 104.5%	86.1 109%	64.9 84.3%

6. 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 those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Number [Percentage of participants]	75.6 96.9%	68.0 90.7%	75.3 97.8%	74.7 94.6%	5.2 6.8%

7. Secondary Outcome

Title	The Percentage of Participants Achieving an 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 2 log10 at Week 12.
Time Frame	Baseline (Day 1) and Week 12

Outcome Measure Data

Analysis Population Description

The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Number [Percentage of participants]	97.4 124.9%	96.0 128%	96.1 124.8%	96.2 121.8%	89.6 116.4%

8. 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 those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Number [Percentage of participants]	91.0 116.7%	93.3 124.4%	93.5 121.4%	94.9 120.1%	55.8 72.5%

9. Secondary 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 who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the EOT.
Time Frame	Up to Week 36 or 52

Outcome Measure Data

Analysis Population Description

The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Number [Percentage of participants]	83.3 106.8%	76.0 101.3%	80.5 104.5%	86.1 109%	66.2 86%

10. Secondary Outcome

Title	Number of Participants With Viral Breakthrough
Description	The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period of the study, defined as a confirmed increase of more than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA more than 100 IU/mL in participants whose plasma HCV RNA level had previously been below the limit of quantification (less than 25 IU/mL detectable or undetectable).
Time Frame	Week 24 or 48

Outcome Measure Data

Analysis Population Description

The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Number [Participants]	5 6.4%	2 2.7%	6 7.8%	2 2.5%	4 5.2%

11. Secondary Outcome

Title	The Number of Participants With Viral Relapse
Description	The table below shows the number of participants who experienced viral relapse, defined as a confirmed detectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.
Time Frame	Up to Week 72

Outcome Measure Data

Analysis Population Description

The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Measure Participants	78	75	77	79	77
Number [Participants]	8 10.3%	14 18.7%	6 7.8%	6 7.6%	11 14.3%

12. Secondary Outcome

Title	The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)
Description	The table below shows the number of participants with abnormal ALT levels at Baseline who achieved ALT levels within the normal range at the EOT.
Time Frame	Baseline (Day 1) up to Week 24 or 48

Outcome Measure Data

Analysis Population Description

The intent-to treat population (defined as those participants who received at least 1 dose of study medication) was used for all efficacy and safety analyses.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48	All TMC435 Treatment Groups
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants in all 4 TMC435 treatment groups combined.
Measure Participants	43	45	48	43	179
Number [Participants]	39 50%	37 49.3%	39 50.6%	35 44.3%	150 194.8%

13. Secondary Outcome

Title	Plasma Concentrations of TMC435
Description	The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for participants in each of the 4 TMC435 treatment groups.
Time Frame	Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study medication with at least 1 post-baseline pharmacokinetic (PK) assessment were included in the PK analysis population.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Measure Participants	77	75	77	78
Coh	240.9	213.6	1123.3	1176.7
Css, av	413.6	374.0	1661.8	1501.6

14. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
Description	The table below shows the median (range) AUC24h values for TMC435 for participants in each of the 4 TMC435 treatment groups. Two blood samples taken at least 2 hours apart from each other for determination of TMC435 plasma pharmacokinetics were obtained in all participants on Weeks 2, 4, 8, 12, 16, and 24 to obtain Bayesian estimates of TMC435 AUC24h (overall exposure).
Time Frame	Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

Outcome Measure Data

Analysis Population Description

Participants who received at least 1 dose of study medication with at least 1 post-baseline pharmacokinetic (PK) assessment were included in the PK analysis population.

Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48	TMC435 75 mg 24 Wks + PR 24/48	TMC435 150 mg 12 Wks + PR 24/48	TMC435 150 mg 24 Wks + PR 24/48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.	Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Measure Participants	77	75	77	78
Median (Full Range) [ng*h/mL]	9926.4	8976.8	39884.0	36038.8

Adverse Events

Time Frame	72 weeks
Adverse Event Reporting Description	All participants who received at least one dose of investigational medication included in safety analysis.
Arm/Group Title	TMC435 75 mg 12 Wks + PR 24/48		TMC435 75 mg 24 Wks + PR 24/48		TMC435 150 mg 12 Wks + PR 24/48		TMC435 150 mg 24 Wks + PR 24/48		Placebo 24 Wks + PR48
Arm/Group Description	Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.		Participants received TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.		Participants received TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.		Participants received TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.		Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
All Cause Mortality
	TMC435 75 mg 12 Wks + PR 24/48		TMC435 75 mg 24 Wks + PR 24/48		TMC435 150 mg 12 Wks + PR 24/48		TMC435 150 mg 24 Wks + PR 24/48		Placebo 24 Wks + PR48
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	TMC435 75 mg 12 Wks + PR 24/48		TMC435 75 mg 24 Wks + PR 24/48		TMC435 150 mg 12 Wks + PR 24/48		TMC435 150 mg 24 Wks + PR 24/48		Placebo 24 Wks + PR48
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/78 (11.5%)		4/75 (5.3%)		4/77 (5.2%)		3/79 (3.8%)		10/77 (13%)
Cardiac disorders
Myocardial infarction	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Myopericarditis	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Endocrine disorders
Hyperthyroidism	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Eye disorders
Ocular vasculitis	0/78 (0%)		1/75 (1.3%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/78 (0%)		0/75 (0%)		0/77 (0%)		1/79 (1.3%)		0/77 (0%)
Colitis	0/78 (0%)		0/75 (0%)		1/77 (1.3%)		0/79 (0%)		0/77 (0%)
Nausea	0/78 (0%)		1/75 (1.3%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Small intestinal obstruction	0/78 (0%)		1/75 (1.3%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Vomiting	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
General disorders
Malaise	0/78 (0%)		0/75 (0%)		1/77 (1.3%)		0/79 (0%)		0/77 (0%)
Asthenia	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Hepatobiliary disorders
Cholecystitis	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Infections and infestations
Incision site cellulitis	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Necrotising fasciitis	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Perihepatic abscess	0/78 (0%)		0/75 (0%)		0/77 (0%)		1/79 (1.3%)		0/77 (0%)
Pneumonia pneumococcal	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Upper respiratory tract infection	0/78 (0%)		1/75 (1.3%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Appendicitis	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Subcutaneous abscess	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Vulval abscess	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Injury, poisoning and procedural complications
Post procedural bile leak	0/78 (0%)		0/75 (0%)		0/77 (0%)		1/79 (1.3%)		0/77 (0%)
Metabolism and nutrition disorders
Malnutrition	0/78 (0%)		0/75 (0%)		1/77 (1.3%)		0/79 (0%)		0/77 (0%)
Type 1 diabetes mellitus	0/78 (0%)		0/75 (0%)		1/77 (1.3%)		0/79 (0%)		0/77 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Spinal disorder	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Myositis	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/78 (0%)		0/75 (0%)		1/77 (1.3%)		0/79 (0%)		0/77 (0%)
Parathyroid tumour benign	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Ovarian neoplasm	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Nervous system disorders
Headache	0/78 (0%)		1/75 (1.3%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Psychiatric disorders
Depression	0/78 (0%)		0/75 (0%)		0/77 (0%)		1/79 (1.3%)		0/77 (0%)
Respiratory, thoracic and mediastinal disorders
Haemoptysis	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Chronic obstructive pulmonary disease	0/78 (0%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		1/77 (1.3%)
Skin and subcutaneous tissue disorders
Cutaneous vasculitis	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		0/79 (0%)		0/77 (0%)
Vascular disorders
Hypertension	0/78 (0%)		0/75 (0%)		0/77 (0%)		1/79 (1.3%)		0/77 (0%)
Other (Not Including Serious) Adverse Events
	TMC435 75 mg 12 Wks + PR 24/48		TMC435 75 mg 24 Wks + PR 24/48		TMC435 150 mg 12 Wks + PR 24/48		TMC435 150 mg 24 Wks + PR 24/48		Placebo 24 Wks + PR48
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/78 (97.4%)		75/75 (100%)		74/77 (96.1%)		77/79 (97.5%)		75/77 (97.4%)
Blood and lymphatic system disorders
Neutropenia	15/78 (19.2%)		23/75 (30.7%)		19/77 (24.7%)		18/79 (22.8%)		16/77 (20.8%)
Anaemia	15/78 (19.2%)		16/75 (21.3%)		17/77 (22.1%)		15/79 (19%)		16/77 (20.8%)
Leukopenia	2/78 (2.6%)		1/75 (1.3%)		1/77 (1.3%)		6/79 (7.6%)		4/77 (5.2%)
Ear and labyrinth disorders
Vertigo	5/78 (6.4%)		1/75 (1.3%)		3/77 (3.9%)		4/79 (5.1%)		4/77 (5.2%)
Endocrine disorders
Hypothyroidism	6/78 (7.7%)		1/75 (1.3%)		1/77 (1.3%)		1/79 (1.3%)		5/77 (6.5%)
Eye disorders
Dry eye	3/78 (3.8%)		2/75 (2.7%)		3/77 (3.9%)		4/79 (5.1%)		4/77 (5.2%)
Vision blurred	3/78 (3.8%)		1/75 (1.3%)		5/77 (6.5%)		3/79 (3.8%)		1/77 (1.3%)
Gastrointestinal disorders
Nausea	26/78 (33.3%)		16/75 (21.3%)		20/77 (26%)		24/79 (30.4%)		21/77 (27.3%)
Diarrhoea	12/78 (15.4%)		14/75 (18.7%)		11/77 (14.3%)		10/79 (12.7%)		12/77 (15.6%)
Vomiting	5/78 (6.4%)		3/75 (4%)		6/77 (7.8%)		8/79 (10.1%)		5/77 (6.5%)
Dry mouth	5/78 (6.4%)		7/75 (9.3%)		3/77 (3.9%)		6/79 (7.6%)		7/77 (9.1%)
Abdominal pain upper	5/78 (6.4%)		4/75 (5.3%)		6/77 (7.8%)		4/79 (5.1%)		4/77 (5.2%)
Dyspepsia	4/78 (5.1%)		5/75 (6.7%)		4/77 (5.2%)		6/79 (7.6%)		6/77 (7.8%)
Constipation	6/78 (7.7%)		1/75 (1.3%)		7/77 (9.1%)		2/79 (2.5%)		5/77 (6.5%)
Abdominal pain	4/78 (5.1%)		3/75 (4%)		4/77 (5.2%)		3/79 (3.8%)		4/77 (5.2%)
Aphthous stomatitis	2/78 (2.6%)		1/75 (1.3%)		4/77 (5.2%)		2/79 (2.5%)		3/77 (3.9%)
General disorders
Fatigue	26/78 (33.3%)		35/75 (46.7%)		32/77 (41.6%)		38/79 (48.1%)		37/77 (48.1%)
Influenza like illness	21/78 (26.9%)		32/75 (42.7%)		18/77 (23.4%)		27/79 (34.2%)		29/77 (37.7%)
Pyrexia	18/78 (23.1%)		15/75 (20%)		15/77 (19.5%)		16/79 (20.3%)		13/77 (16.9%)
Asthenia	20/78 (25.6%)		12/75 (16%)		18/77 (23.4%)		13/79 (16.5%)		16/77 (20.8%)
Irritability	10/78 (12.8%)		7/75 (9.3%)		14/77 (18.2%)		11/79 (13.9%)		8/77 (10.4%)
Chills	4/78 (5.1%)		8/75 (10.7%)		6/77 (7.8%)		7/79 (8.9%)		8/77 (10.4%)
Injection site erythema	4/78 (5.1%)		8/75 (10.7%)		5/77 (6.5%)		7/79 (8.9%)		4/77 (5.2%)
Injection site reaction	5/78 (6.4%)		4/75 (5.3%)		2/77 (2.6%)		2/79 (2.5%)		4/77 (5.2%)
Pain	6/78 (7.7%)		2/75 (2.7%)		2/77 (2.6%)		1/79 (1.3%)		2/77 (2.6%)
Hepatobiliary disorders
Hyperbilirubinaemia	2/78 (2.6%)		0/75 (0%)		5/77 (6.5%)		2/79 (2.5%)		2/77 (2.6%)
Infections and infestations
Nasopharyngitis	1/78 (1.3%)		5/75 (6.7%)		4/77 (5.2%)		4/79 (5.1%)		6/77 (7.8%)
Influenza	1/78 (1.3%)		5/75 (6.7%)		4/77 (5.2%)		3/79 (3.8%)		3/77 (3.9%)
Urinary tract infection	2/78 (2.6%)		2/75 (2.7%)		1/77 (1.3%)		5/79 (6.3%)		2/77 (2.6%)
Sinusitis	4/78 (5.1%)		0/75 (0%)		1/77 (1.3%)		2/79 (2.5%)		2/77 (2.6%)
Investigations
Weight decreased	7/78 (9%)		3/75 (4%)		3/77 (3.9%)		6/79 (7.6%)		3/77 (3.9%)
Neutrophil count decreased	1/78 (1.3%)		5/75 (6.7%)		5/77 (6.5%)		4/79 (5.1%)		4/77 (5.2%)
Blood bilirubin increased	1/78 (1.3%)		0/75 (0%)		5/77 (6.5%)		5/79 (6.3%)		0/77 (0%)
Alanine aminotransferase increased	3/78 (3.8%)		1/75 (1.3%)		1/77 (1.3%)		5/79 (6.3%)		0/77 (0%)
Aspartate aminotransferase increased	2/78 (2.6%)		1/75 (1.3%)		1/77 (1.3%)		6/79 (7.6%)		0/77 (0%)
Gamma-glutamyltransferase increased	1/78 (1.3%)		0/75 (0%)		0/77 (0%)		4/79 (5.1%)		0/77 (0%)
Metabolism and nutrition disorders
Anorexia	10/78 (12.8%)		12/75 (16%)		11/77 (14.3%)		9/79 (11.4%)		11/77 (14.3%)
Decreased appetite	6/78 (7.7%)		3/75 (4%)		4/77 (5.2%)		4/79 (5.1%)		6/77 (7.8%)
Musculoskeletal and connective tissue disorders
Myalgia	17/78 (21.8%)		12/75 (16%)		16/77 (20.8%)		10/79 (12.7%)		17/77 (22.1%)
Arthralgia	11/78 (14.1%)		12/75 (16%)		14/77 (18.2%)		16/79 (20.3%)		11/77 (14.3%)
Back pain	5/78 (6.4%)		8/75 (10.7%)		10/77 (13%)		7/79 (8.9%)		7/77 (9.1%)
Muscle spasms	4/78 (5.1%)		2/75 (2.7%)		1/77 (1.3%)		4/79 (5.1%)		4/77 (5.2%)
Musculoskeletal pain	1/78 (1.3%)		4/75 (5.3%)		0/77 (0%)		3/79 (3.8%)		6/77 (7.8%)
Pain in extremity	1/78 (1.3%)		1/75 (1.3%)		1/77 (1.3%)		3/79 (3.8%)		5/77 (6.5%)
Nervous system disorders
Headache	41/78 (52.6%)		34/75 (45.3%)		35/77 (45.5%)		32/79 (40.5%)		40/77 (51.9%)
Dizziness	10/78 (12.8%)		3/75 (4%)		4/77 (5.2%)		12/79 (15.2%)		6/77 (7.8%)
Disturbance in attention	5/78 (6.4%)		3/75 (4%)		6/77 (7.8%)		4/79 (5.1%)		3/77 (3.9%)
Dysgeusia	6/78 (7.7%)		1/75 (1.3%)		5/77 (6.5%)		4/79 (5.1%)		5/77 (6.5%)
Paraesthesia	1/78 (1.3%)		0/75 (0%)		4/77 (5.2%)		1/79 (1.3%)		1/77 (1.3%)
Syncope	1/78 (1.3%)		2/75 (2.7%)		2/77 (2.6%)		1/79 (1.3%)		4/77 (5.2%)
Migraine	0/78 (0%)		0/75 (0%)		1/77 (1.3%)		4/79 (5.1%)		0/77 (0%)
Hypoaesthesia	0/78 (0%)		0/75 (0%)		1/77 (1.3%)		1/79 (1.3%)		4/77 (5.2%)
Psychiatric disorders
Insomnia	19/78 (24.4%)		14/75 (18.7%)		23/77 (29.9%)		13/79 (16.5%)		23/77 (29.9%)
Depression	8/78 (10.3%)		4/75 (5.3%)		9/77 (11.7%)		11/79 (13.9%)		14/77 (18.2%)
Sleep disorder	8/78 (10.3%)		3/75 (4%)		4/77 (5.2%)		7/79 (8.9%)		4/77 (5.2%)
Mood altered	4/78 (5.1%)		5/75 (6.7%)		1/77 (1.3%)		8/79 (10.1%)		7/77 (9.1%)
Depressed mood	4/78 (5.1%)		4/75 (5.3%)		3/77 (3.9%)		6/79 (7.6%)		3/77 (3.9%)
Anxiety	5/78 (6.4%)		2/75 (2.7%)		4/77 (5.2%)		4/79 (5.1%)		5/77 (6.5%)
Mood swings	4/78 (5.1%)		0/75 (0%)		1/77 (1.3%)		5/79 (6.3%)		3/77 (3.9%)
Respiratory, thoracic and mediastinal disorders
Cough	18/78 (23.1%)		9/75 (12%)		12/77 (15.6%)		13/79 (16.5%)		15/77 (19.5%)
Dyspnoea	12/78 (15.4%)		8/75 (10.7%)		7/77 (9.1%)		6/79 (7.6%)		6/77 (7.8%)
Dyspnoea exertional	6/78 (7.7%)		9/75 (12%)		10/77 (13%)		5/79 (6.3%)		7/77 (9.1%)
Oropharyngeal pain	5/78 (6.4%)		3/75 (4%)		4/77 (5.2%)		4/79 (5.1%)		8/77 (10.4%)
Skin and subcutaneous tissue disorders
Pruritus	25/78 (32.1%)		17/75 (22.7%)		30/77 (39%)		24/79 (30.4%)		35/77 (45.5%)
Rash	21/78 (26.9%)		10/75 (13.3%)		16/77 (20.8%)		18/79 (22.8%)		18/77 (23.4%)
Dry skin	12/78 (15.4%)		12/75 (16%)		17/77 (22.1%)		22/79 (27.8%)		14/77 (18.2%)
Alopecia	20/78 (25.6%)		11/75 (14.7%)		11/77 (14.3%)		11/79 (13.9%)		16/77 (20.8%)
Erythema	3/78 (3.8%)		2/75 (2.7%)		5/77 (6.5%)		5/79 (6.3%)		4/77 (5.2%)
Eczema	7/78 (9%)		1/75 (1.3%)		3/77 (3.9%)		3/79 (3.8%)		5/77 (6.5%)
Pruritus generalised	3/78 (3.8%)		2/75 (2.7%)		3/77 (3.9%)		6/79 (7.6%)		5/77 (6.5%)
Night sweats	6/78 (7.7%)		1/75 (1.3%)		1/77 (1.3%)		2/79 (2.5%)		1/77 (1.3%)
Dermatitis	1/78 (1.3%)		4/75 (5.3%)		1/77 (1.3%)		1/79 (1.3%)		1/77 (1.3%)
Hyperhidrosis	1/78 (1.3%)		3/75 (4%)		0/77 (0%)		3/79 (3.8%)		4/77 (5.2%)
Vascular disorders
Hot flush	1/78 (1.3%)		0/75 (0%)		2/77 (2.6%)		5/79 (6.3%)		2/77 (2.6%)
Hypertension	0/78 (0%)		1/75 (1.3%)		1/77 (1.3%)		4/79 (5.1%)		2/77 (2.6%)

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.