Trial Outcomes & Findings for Peak Study - A Study of Pegasys (Peginterferon Alfa-2a (40KD)) in Combination With Copegus (Ribavirin) in Interferon-Naive Patients With Chronic Hepatitis C (CHC). (NCT NCT00087607)

Last Updated: 2016-07-01

Results Overview

The viral load was determined quantitatively and qualitatively by Hepatitis C virus (HCV)-polymerase chain reaction (PCR). HCV RNA was measured qualitatively using the Roche amplicor PCR assay (lower limit of detection 60 international units per milliliter (U/mL), changed from 50 IU/mL with amendment B) and quantitatively using the Roche amplicor HCV monitor® test v2.0 (lower limit of quantification 600 IU/mL). Log transformations were performed for HCV RNA, and the analyses were done on a log10 scale. The average value of the difference between viral load levels in the serum from baseline to Week 12, expressed in terms of a logarithmic scale with base 10, are presented.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

385 participants

Primary outcome timeframe

From Baseline to Week 12

Results posted on

2016-07-01

Participant Flow

This study was conducted from January 2004 to April 2006 at 41 centers in the United States.

This study planned to enroll 344 participants (172 in each group). Of the total randomized 385 participants who met the eligibility criteria, five did not receive study treatment and were not included in any analysis population.

Participant milestones

Participant milestones
Measure	Peginterferon Alfa-2a + Ribavirin Participants received Peginterferon alfa-2a (40 kD) \[Pegasys\] at a dosage of 180 microgram (μg), subcutaneously (SC), once a week plus Ribavirin \[Copegus\] 1000 or 1200 milligram (mg)/day), orally, \[according to body weight, lesser than or greater than/equal to (\< or \>/=) 75 kilogram (kg), respectively\] twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin Participants received Peginterferon alfa-2b (12 kD) \[PEG-Intron\] at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin \[Rebetol\] 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Overall Study STARTED	192	193
Overall Study COMPLETED	70	71
Overall Study NOT COMPLETED	122	122

Reasons for withdrawal

Reasons for withdrawal
Measure	Peginterferon Alfa-2a + Ribavirin Participants received Peginterferon alfa-2a (40 kD) \[Pegasys\] at a dosage of 180 microgram (μg), subcutaneously (SC), once a week plus Ribavirin \[Copegus\] 1000 or 1200 milligram (mg)/day), orally, \[according to body weight, lesser than or greater than/equal to (\< or \>/=) 75 kilogram (kg), respectively\] twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin Participants received Peginterferon alfa-2b (12 kD) \[PEG-Intron\] at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin \[Rebetol\] 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Overall Study Adverse Event	14	24
Overall Study Death	0	1
Overall Study Insufficient Therapeutic Response	53	42
Overall Study Failure to return	21	17
Overall Study Withdrew Consent	12	16
Overall Study Administrative	12	12
Overall Study Refused Treatment	5	7
Overall Study Other Protocol Violation	5	2
Overall Study Violation of Selection Criteria at Entry	0	1

Baseline Characteristics

Peak Study - A Study of Pegasys (Peginterferon Alfa-2a (40KD)) in Combination With Copegus (Ribavirin) in Interferon-Naive Patients With Chronic Hepatitis C (CHC).

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Peginterferon Alfa-2a + Ribavirin n=189 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=191 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Total n=380 Participants Total of all reporting groups
Age, Continuous	46.9 years STANDARD_DEVIATION 7.18 • n=5 Participants	48.4 years STANDARD_DEVIATION 7.80 • n=7 Participants	47.6 years STANDARD_DEVIATION 7.52 • n=5 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	55 Participants n=7 Participants	123 Participants n=5 Participants
Sex: Female, Male Male	121 Participants n=5 Participants	136 Participants n=7 Participants	257 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline to Week 12

Population: The analysis population was ITT Population. The ITT Population included all participants who were randomized and received at least one dose of study medication (PEG-IFN or ribavirin). Data using ITT Population are presented below.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=172 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=169 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Change From Baseline in Viral Load (log10 Reduction) at Week 12	-3.26 log (IU/mL) Standard Error 0.12	-3.27 log (IU/mL) Standard Error 0.14

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 8

The viral load was determined quantitatively and qualitatively by HCV-PCR. HCV RNA was measured qualitatively using the Roche amplicor PCR assay (lower limit of detection 60 IU/mL, changed from 50 IU/mL with amendment B) and quantitatively using the Roche amplicor HCV monitor® test v2.0 (lower limit of quantification 600 IU/mL). Log transformations were performed for HCV RNA, and the analyses were done on a log10 scale. The average value of the difference between viral load levels in the serum from baseline to week 4 and week 8, expressed in terms of a logarithmic scale with base 10 are presented.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=181 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=178 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Mean Change From Baseline in Viral Load (log10 Reduction) at Week 4 and Week 8 Week 4; n = 181, 178	-1.95 log (IU/mL) Standard Error 0.10	-2.22 log (IU/mL) Standard Error 0.12
Mean Change From Baseline in Viral Load (log10 Reduction) at Week 4 and Week 8 Week 8; n = 178, 175	-2.88 log (IU/mL) Standard Error 0.12	-2.95 log (IU/mL) Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline, up to Week 12

The viral load was determined quantitatively and qualitatively by HCV-PCR. HCV RNA was measured qualitatively using the Roche amplicor PCR assay (lower limit of detection 60 IU/mL, changed from 50 IU/mL with amendment B) and quantitatively using the Roche amplicor HCV monitor® test v2.0 (lower limit of quantification 600 IU/mL). Log transformations were performed for HCV RNA, and the analyses were done on a log10 scale. The viral load levels in the serum at baseline and for each week, were expressed in terms of a logarithmic scale with base 10, and averaged for all participants.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=189 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=191 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Weekly Viral Load Assessed at Drug Trough Week 6; n = 179, 177	3.96 log (IU/mL) Standard Deviation 1.53	3.78 log (IU/mL) Standard Deviation 1.66
Weekly Viral Load Assessed at Drug Trough Week 10; n = 175, 171	3.31 log (IU/mL) Standard Deviation 1.53	3.34 log (IU/mL) Standard Deviation 1.74
Weekly Viral Load Assessed at Drug Trough Baseline; n = 189, 191	6.46 log (IU/mL) Standard Deviation 0.35	6.48 log (IU/mL) Standard Deviation 0.37
Weekly Viral Load Assessed at Drug Trough Week 1; n = 181, 185	5.69 log (IU/mL) Standard Deviation 0.87	5.70 log (IU/mL) Standard Deviation 0.89
Weekly Viral Load Assessed at Drug Trough Week 2; n = 182, 184	5.26 log (IU/mL) Standard Deviation 1.11	5.12 log (IU/mL) Standard Deviation 1.25
Weekly Viral Load Assessed at Drug Trough Week 3; n = 179, 183	4.84 log (IU/mL) Standard Deviation 1.31	4.64 log (IU/mL) Standard Deviation 1.47
Weekly Viral Load Assessed at Drug Trough Week 4; n = 181, 178	4.51 log (IU/mL) Standard Deviation 1.42	4.25 log (IU/mL) Standard Deviation 1.57
Weekly Viral Load Assessed at Drug Trough Week 5; n = 182, 179	4.20 log (IU/mL) Standard Deviation 1.48	4.01 log (IU/mL) Standard Deviation 1.61
Weekly Viral Load Assessed at Drug Trough Week 7; n = 178, 175	3.73 log (IU/mL) Standard Deviation 1.54	3.64 log (IU/mL) Standard Deviation 1.67
Weekly Viral Load Assessed at Drug Trough Week 8; n = 178, 175	3.57 log (IU/mL) Standard Deviation 1.55	3.53 log (IU/mL) Standard Deviation 1.67
Weekly Viral Load Assessed at Drug Trough Week 9; n = 171, 170	3.44 log (IU/mL) Standard Deviation 1.56	3.44 log (IU/mL) Standard Deviation 1.74
Weekly Viral Load Assessed at Drug Trough Week 11; n = 173, 167	3.23 log (IU/mL) Standard Deviation 1.56	3.30 log (IU/mL) Standard Deviation 1.77
Weekly Viral Load Assessed at Drug Trough Week 12; n = 172, 169	3.18 log (IU/mL) Standard Deviation 1.54	3.21 log (IU/mL) Standard Deviation 1.77

SECONDARY outcome

Timeframe: From Week -1 to Week 12

The area under the HCV-RNA curve (HCV AUC) was defined as the area under the polygonal line defined by the HCV RNA values from the beginning of the time window to the end of the time window. Each of these areas was a sum of one or more trapezoids determined from the concentrations over the 7-day interval. The HCV AUC to Week 12 was the sum of the 12 weekly HCV AUCs divided by the time (12 weeks). Summary of weekly HCV AUC values estimated from the two adjacent pre-dose assessments are presented.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=188 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=190 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 5, n = 182, 181	4.3 log 10 IU/mL Standard Deviation 1.45	4.1 log 10 IU/mL Standard Deviation 1.57
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 9, n = 176, 173	3.5 log 10 IU/mL Standard Deviation 1.54	3.5 log 10 IU/mL Standard Deviation 1.68
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 10, n = 176, 171	3.4 log 10 IU/mL Standard Deviation 1.54	3.4 log 10 IU/mL Standard Deviation 1.72
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 11, n = 174, 170	3.3 log 10 IU/mL Standard Deviation 1.55	3.3 log 10 IU/mL Standard Deviation 1.73
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 12, n = 171, 169	3.2 log 10 IU/mL Standard Deviation 1.55	3.2 log 10 IU/mL Standard Deviation 1.74
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week -1, n = 188, 190	6.5 log 10 IU/mL Standard Deviation 0.40	6.5 log 10 IU/mL Standard Deviation 0.41
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 1, n = 186, 188	6.1 log 10 IU/mL Standard Deviation 0.55	6.1 log 10 IU/mL Standard Deviation 0.56
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 2, n = 185, 187	5.5 log 10 IU/mL Standard Deviation 0.97	5.4 log 10 IU/mL Standard Deviation 1.04
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 3, n = 184, 184	5.0 log 10 IU/mL Standard Deviation 1.20	4.9 log 10 IU/mL Standard Deviation 1.33
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 4, n = 183, 181	4.7 log 10 IU/mL Standard Deviation 1.36	4.4 log 10 IU/mL Standard Deviation 1.48
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 6, n = 180, 179	4.1 log 10 IU/mL Standard Deviation 1.48	3.9 log 10 IU/mL Standard Deviation 1.63
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 7, n = 180, 177	3.8 log 10 IU/mL Standard Deviation 1.52	3.7 log 10 IU/mL Standard Deviation 1.66
The Area Under the HCV-RNA Curve Estimated From the Two Adjacent Pre-dose Assessments at Each Week Week 8, n = 178, 175	3.6 log 10 IU/mL Standard Deviation 1.54	3.6 log 10 IU/mL Standard Deviation 1.65

SECONDARY outcome

Timeframe: Baseline, Week 1 to Week 12

The HCV AUC was calculated for each week as the area under the polygonal line defined by the HCV RNA values from the beginning of the time window to the end of the time window. Each of these areas was a sum of one or more trapezoids determined from the concentrations over the 7-day interval. The weekly AUCMB was calculated by subtracting the Week -1 HCV AUC (i.e., baseline) from the weekly HCV AUC and presented.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=186 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=188 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 1; n = 186, 188	0.4 log (IU*week/mL) Standard Deviation 0.40	0.4 log (IU*week/mL) Standard Deviation 0.43
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 8; n = 178, 175	2.8 log (IU*week/mL) Standard Deviation 1.53	2.9 log (IU*week/mL) Standard Deviation 1.65
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 9; n = 176, 173	3.0 log (IU*week/mL) Standard Deviation 1.55	3.0 log (IU*week/mL) Standard Deviation 1.69
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 10; n = 176, 171	3.1 log (IU*week/mL) Standard Deviation 1.55	3.1 log (IU*week/mL) Standard Deviation 1.75
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 11; n = 174, 170	3.2 log (IU*week/mL) Standard Deviation 1.56	3.2 log (IU*week/mL) Standard Deviation 1.76
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 12; n = 171, 169	3.2 log (IU*week/mL) Standard Deviation 1.56	3.2 log (IU*week/mL) Standard Deviation 1.77
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 2; n = 185, 187	1.0 log (IU*week/mL) Standard Deviation 0.90	1.1 log (IU*week/mL) Standard Deviation 0.99
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 3; n = 184, 184	1.4 log (IU*week/mL) Standard Deviation 1.15	1.6 log (IU*week/mL) Standard Deviation 1.30
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 4; n = 183, 181	1.8 log (IU*week/mL) Standard Deviation 1.33	2.0 log (IU*week/mL) Standard Deviation 1.46
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 5; n = 182, 181	2.1 log (IU*week/mL) Standard Deviation 1.42	2.3 log (IU*week/mL) Standard Deviation 1.56
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 6; n = 180, 179	2.4 log (IU*week/mL) Standard Deviation 1.47	2.6 log (IU*week/mL) Standard Deviation 1.62
Mean Value of Area Under the HCV-RNA Curve Minus Baseline From Week 1 to Week 12 Week 7; n = 180, 177	2.6 log (IU*week/mL) Standard Deviation 1.51	2.8 log (IU*week/mL) Standard Deviation 1.66

SECONDARY outcome

Timeframe: Up to Week 12

Population: The analysis population was ITT Population. The ITT Population included all participants who were randomized and received at least one dose of study medication (PEG-IFN or ribavirin).

The area under the HCV-RNA curve (HCV AUC) was calculated for each week as the area under the polygonal line defined by the HCV RNA values from the beginning of the window to the end of the window. Each of these areas was a sum of one or more trapezoids determined from the concentrations over the 7-day interval. The weekly AUCMB was calculated by subtracting the Week -1 HCV AUC (i.e., baseline) from the weekly HCV AUC. The HCV AUCMB to Week 12 was the sum of the 12 weekly HCV AUCMBs divided by the time (12 weeks).

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=171 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=169 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Cumulative Viral Absolute Area Under the HCV RNA Curve Minus Baseline Averaged Over the 12-week Period	26.9 log10 IU/mL Standard Deviation 15.34	28.7 log10 IU/mL Standard Deviation 16.66

SECONDARY outcome

Timeframe: Week 1 and Week 8

The area under the HCV-RNA curve (HCV AUC) was defined as the area under the polygonal line defined by the HCV RNA values from the beginning of the window to the end of the window. For the frequent-sampling cohort, HCV AUCs over 7 days were calculated for Weeks 1 and 8, with intervals calculated beginning at the dose after which the frequent sampling began (different from the 7-day calendar period used for other AUC calculations). The AUCs for Weeks 1 and 8 in the frequent-sampling cohort (Sparse samples \[SS\] and frequent samples \[FS\]) were calculated using the trapezoidal rule.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=12 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=13 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Weekly Viral Absolute Area Under the HCV RNA Curve Estimated in the Frequent-sampling Cohort for Weeks 1 and 8 SS, Week 1; n = 12, 13	6.0 log (IU*week/mL) Standard Deviation 0.45	6.0 log (IU*week/mL) Standard Deviation 0.44
Weekly Viral Absolute Area Under the HCV RNA Curve Estimated in the Frequent-sampling Cohort for Weeks 1 and 8 SS, Week 8; n = 12, 12	3.4 log (IU*week/mL) Standard Deviation 1.65	3.5 log (IU*week/mL) Standard Deviation 1.68
Weekly Viral Absolute Area Under the HCV RNA Curve Estimated in the Frequent-sampling Cohort for Weeks 1 and 8 FS, Week 1; n = 12, 13	5.8 log (IU*week/mL) Standard Deviation 0.52	5.5 log (IU*week/mL) Standard Deviation 0.91
Weekly Viral Absolute Area Under the HCV RNA Curve Estimated in the Frequent-sampling Cohort for Weeks 1 and 8 FS, Week 8; n = 12, 12	3.3 log (IU*week/mL) Standard Deviation 1.63	3.5 log (IU*week/mL) Standard Deviation 1.60

SECONDARY outcome

Timeframe: From Week 1 to Week 12

Population: The analysis population was ITT Population. The ITT Population included all participants who were randomized and received at least one dose of study medication (PEG-IFN or ribavirin).

The virological response was determined as the proportion/percentage of participants with a ≥ 2-log10 decrease or undetectable HCV RNA at each week. Detection of \>= 2-log10 decrease of \<60 IU/mL HCV-RNA was done by amplicor PCR assay at each week. Detection of \>=2-log10 decrease or undetectable HCV RNA at Week 12 was considered an early virological response (EVR).

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=189 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=191 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 1	6.9 percentage of participants Interval 3.3 to 10.5	9.9 percentage of participants Interval 5.7 to 14.2
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 2	20.1 percentage of participants Interval 14.4 to 25.8	30.4 percentage of participants Interval 23.8 to 36.9
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 6	53.4 percentage of participants Interval 46.3 to 60.6	55.5 percentage of participants Interval 48.4 to 62.5
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 7	57.1 percentage of participants Interval 50.1 to 64.2	57.6 percentage of participants Interval 50.6 to 64.6
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 8	61.4 percentage of participants Interval 54.4 to 68.3	59.2 percentage of participants Interval 52.2 to 66.1
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 3	31.7 percentage of participants Interval 25.1 to 38.4	42.4 percentage of participants Interval 35.4 to 49.4
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 4	41.8 percentage of participants Interval 34.8 to 48.8	49.2 percentage of participants Interval 42.1 to 56.3
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 5	46.6 percentage of participants Interval 39.4 to 53.7	53.4 percentage of participants Interval 46.3 to 60.5
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 9	59.8 percentage of participants Interval 52.8 to 66.8	57.6 percentage of participants Interval 50.6 to 64.6
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 10	65.6 percentage of participants Interval 58.8 to 72.4	60.2 percentage of participants Interval 53.3 to 67.2
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 11	65.1 percentage of participants Interval 58.3 to 71.9	59.7 percentage of participants Interval 52.7 to 66.6
Percentage of Participants With a ≥ 2-log10 Decrease or Undetectable (< 60 International Units Per Milliliter) HCV RNA at Each Visit Week 12	66.1 percentage of participants Interval 59.4 to 72.9	63.4 percentage of participants Interval 56.5 to 70.2

SECONDARY outcome

Timeframe: From Week 1 to Week 12

Population: The analysis population was ITT Population. The ITT Population included all participants who were randomized and received at least one dose of study medication (PEG-IFN or ribavirin).

The viral load was determined quantitatively and qualitatively by HCV-polymerase chain reaction (PCR). Qualitative viral titers will be assessed by Roche amplicor HCV Monitor® test v2.0 (\< 600 IU/mL). The virological response was determined as the percentage of participants with undetectable HCV RNA at each week. A \<60 IU/mL HCV-RNA was measured by amplicor PCR assay.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=189 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=191 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 1	0.5 percentage of participants Interval -0.5 to 1.6	0.5 percentage of participants Interval -0.5 to 1.5
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 2	1.6 percentage of participants Interval -0.2 to 3.4	2.1 percentage of participants Interval 0.1 to 4.1
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 3	2.6 percentage of participants Interval 0.4 to 4.9	6.3 percentage of participants Interval 2.8 to 9.7
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 4	7.4 percentage of participants Interval 3.7 to 11.1	11.5 percentage of participants Interval 7.0 to 16.0
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 5	11.1 percentage of participants Interval 6.6 to 15.6	15.7 percentage of participants Interval 10.5 to 20.9
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 11	39.2 percentage of participants Interval 32.2 to 46.1	41.9 percentage of participants Interval 34.9 to 48.9
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 6	16.9 percentage of participants Interval 11.6 to 22.3	23.6 percentage of participants Interval 17.5 to 29.6
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 7	22.2 percentage of participants Interval 16.3 to 28.1	26.7 percentage of participants Interval 20.4 to 33.0
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 8	25.9 percentage of participants Interval 19.7 to 32.2	29.3 percentage of participants Interval 22.9 to 35.8
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 9	29.6 percentage of participants Interval 23.1 to 36.1	35.6 percentage of participants Interval 28.8 to 42.4
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 10	34.9 percentage of participants Interval 28.1 to 41.7	40.3 percentage of participants Interval 33.4 to 47.3
Percentage of Participants With Undetectable HCV RNA (< 60 International Units/Milliliter) at Each Visit Week 12	39.2 percentage of participants Interval 32.2 to 46.1	44.0 percentage of participants Interval 36.9 to 51.0

SECONDARY outcome

Timeframe: Baseline, up to Week 12

Population: The analysis population was the Safety Population. The Safety Population included all participants who were randomized, received at least one dose of study medication (PEG-IFN or ribavirin), and had at least one post-baseline safety assessment (defined as clinical adverse event, laboratory or vital sign data, or physical examination finding).

The values outside the marked reference range for any hematology parameter that represents a defined, clinically relevant change from baseline are considered marked hematology abnormalities. The Roche standard reference ranges for the hematology parameters for which subjects had marked abnormalities were hematocrit \[(RR) is 0.42 - 0.52 (fraction)\], hemoglobin (RR is 13.0 - 18.0 gram/deciliter), platelets (RR is 150 - 450 10\^9 cells/L), white blood cells (WBC) (RR is 4.3 - 10.8 10\^9 cells/L), basophils (RR is 0.00 - 0.15 10\^9 cells/L), lymphocytes (RR is 1.50 - 4.00 10\^9 cells/L), monocytes (RR is 0.20 - 0.95 10\^9 cells/L), neutrophils (RR is 1.83 - 7.25 10\^9 cells/L), prothrombin time (PT) (RR is 9 - 13 seconds), partial thromboplastin time (Partial Throm.) (Time) (RR is 25.0 - 38.0 seconds) and PT International normalized ratio (INR) \[RR is 0.70 - 1.30 (ratio)\]. Summary data of number of participants with only marked hematology abnormalities are presented.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=187 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=190 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Number of Participants With Marked Hematologic Abnormalities Partial Throm.-High	3 participants	1 participants
Number of Participants With Marked Hematologic Abnormalities PT (ProThrom Time)-High	15 participants	25 participants
Number of Participants With Marked Hematologic Abnormalities PT (INR)-High	5 participants	6 participants
Number of Participants With Marked Hematologic Abnormalities Hemoglobin-Low	64 participants	69 participants
Number of Participants With Marked Hematologic Abnormalities Lymphocytes-Low	77 participants	75 participants
Number of Participants With Marked Hematologic Abnormalities Monocytes-Low	1 participants	1 participants
Number of Participants With Marked Hematologic Abnormalities Neutrophils-Low	136 participants	137 participants
Number of Participants With Marked Hematologic Abnormalities Platelets-Low	41 participants	31 participants
Number of Participants With Marked Hematologic Abnormalities Hematocrit -Low	72 participants	90 participants
Number of Participants With Marked Hematologic Abnormalities WBC-High	2 participants	0 participants
Number of Participants With Marked Hematologic Abnormalities WBC-Low	124 participants	119 participants
Number of Participants With Marked Hematologic Abnormalities Basophils-High	2 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, up to Week 12

Values outside the marked RR for biochemical test parameters that represent a defined, clinically relevant change from baseline are considered marked biochemical test abnormalities. Roche's standard RR for biochemical parameters were used for this analysis. The biochemical test parameters with marked abnormalities were alanine aminotransferase (ALAT) (RR is 0 - 30 units per liter \[U/L\]), aspartate aminotransferase (ASAT) (RR is 0 - 25 U/L), gamma-glutamyl transferase (GGT) (RR is 0 - 60 U/L), total bilirubin (RR is 0 - 17 micromole/liter \[umol/L\]), creatinine (RR is 0 - 133 umol/L), total protein (RR is 60 - 80 g/L), triglycerides (RR is 0.45 - 1.70 millimole/liter \[mmol/L\]), chloride (RR is 100 - 108 mmol/L), potassium (RR is 3.5 - 5.0 mmol/L), sodium (RR is 133 - 145 mmol/L), calcium (RR is 2.10 - 2.60 mmol/L), random glucose (RR is 3.89 - 7.83 mmol/L), uric acid (140 - 500 umol/L). Summary data of number of participants with only marked biochemical test abnormalities are presented.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=187 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=190 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Number of Participants With Marked Biochemical Test Abnormalities ALAT-High	5 participants	12 participants
Number of Participants With Marked Biochemical Test Abnormalities ASAT- High	17 participants	11 participants
Number of Participants With Marked Biochemical Test Abnormalities GG- High	23 participants	18 participants
Number of Participants With Marked Biochemical Test Abnormalities Total Bilirubin- High	8 participants	8 participants
Number of Participants With Marked Biochemical Test Abnormalities Creatinine- High	0 participants	1 participants
Number of Participants With Marked Biochemical Test Abnormalities Total Protein- Low	1 participants	4 participants
Number of Participants With Marked Biochemical Test Abnormalities Triglycerides- High	89 participants	98 participants
Number of Participants With Marked Biochemical Test Abnormalities Chloride- Low	2 participants	5 participants
Number of Participants With Marked Biochemical Test Abnormalities Potassium- Low	1 participants	2 participants
Number of Participants With Marked Biochemical Test Abnormalities Sodium- Low	1 participants	5 participants
Number of Participants With Marked Biochemical Test Abnormalities Calcium- Low	5 participants	9 participants
Number of Participants With Marked Biochemical Test Abnormalities Glucose Random- High	3 participants	5 participants
Number of Participants With Marked Biochemical Test Abnormalities Uric Acid- High	8 participants	21 participants

SECONDARY outcome

Timeframe: Baseline, up to Week 12

Values outside the marked reference ranges for thyroid function test parameters that represent a defined, clinically relevant change from baseline are considered marked thyroid function test abnormalities. Roche's standard reference ranges for thyroid function test parameters were used for the analysis. The thyroid function parameters with marked abnormalities were triiodothyronine (T3) (RR is 1.20 - 3.00 nanomole/liter \[nmol/L\]), thyroxine (T4) (RR is 51 - 154 nmol/L) and thyroid stimulating hormone (TSH) (RR is 0.0 - 5.0 milliunits per liter \[mU/L\]). Summary data of number of participants with only marked abnormalities in thyroid function tests are presented.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=187 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=190 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Number of Participants With Marked Abnormalities in Thyroid Function Tests T3-High	4 participants	3 participants
Number of Participants With Marked Abnormalities in Thyroid Function Tests T4-High	4 participants	2 participants
Number of Participants With Marked Abnormalities in Thyroid Function Tests TSH-High	1 participants	1 participants

SECONDARY outcome

Timeframe: From Week 1 to Week 12

The weekly Interferon (IFN) concentrations were calculated using the trapezoid rule. The trough IFN concentration was analyzed using an enzyme-linked immunosorbent assay (ELISA), with limits of quantification of 250 picograms per milliliter \[pg/mL\] for Pegasys and 150 pg/mL for PEG-Intron respectively.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=152 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=182 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Mean Trough Interferon Concentrations at Each Week Week 3; n = 152, 181	11082 pg/mL Standard Error 438.4	125 pg/mL Standard Error 8.8
Mean Trough Interferon Concentrations at Each Week Week 1; n = 137, 179	6730 pg/mL Standard Error 289.3	119 pg/mL Standard Error 11.0
Mean Trough Interferon Concentrations at Each Week Week 2; n = 152, 182	9530 pg/mL Standard Error 399.6	144 pg/mL Standard Error 12.1
Mean Trough Interferon Concentrations at Each Week Week 4; n = 152, 178	12089 pg/mL Standard Error 439.0	150 pg/mL Standard Error 16.7
Mean Trough Interferon Concentrations at Each Week Week 5; n = 150, 177	12529 pg/mL Standard Error 454.7	163 pg/mL Standard Error 16.2
Mean Trough Interferon Concentrations at Each Week Week 6; n = 150, 173	12686 pg/mL Standard Error 429.9	143 pg/mL Standard Error 10.4
Mean Trough Interferon Concentrations at Each Week Week 7; n = 150, 175	12852 pg/mL Standard Error 438.8	162 pg/mL Standard Error 14.6
Mean Trough Interferon Concentrations at Each Week Week 8; n = 146, 174	12781 pg/mL Standard Error 448.3	147 pg/mL Standard Error 10.4
Mean Trough Interferon Concentrations at Each Week Week 9; n = 144, 171	12781 pg/mL Standard Error 422.2	167 pg/mL Standard Error 17.3
Mean Trough Interferon Concentrations at Each Week Week 10; n = 145, 168	12499 pg/mL Standard Error 397.3	156 pg/mL Standard Error 12.2
Mean Trough Interferon Concentrations at Each Week Week 11; n = 144, 165	12689 pg/mL Standard Error 409.2	163 pg/mL Standard Error 10.9
Mean Trough Interferon Concentrations at Each Week Week 12; n = 144, 168	12846 pg/mL Standard Error 450.9	154 pg/mL Standard Error 11.4

SECONDARY outcome

Timeframe: Week 1 and Week 8

Area Under the Curve (AUC) for Interferon (IFN) for Week 1 and Week 8 in the frequent-sampling cohort were calculated using the trapezoidal rule.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=8 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=5 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Area Under the Curve for Interferon in the Frequent-Sampling Cohort Week 8; n = 7, 5	14399.9 week*pg/mL Standard Deviation 5658.05	472.1 week*pg/mL Standard Deviation 62.32
Area Under the Curve for Interferon in the Frequent-Sampling Cohort Week 1; n = 8, 4	6376.0 week*pg/mL Standard Deviation 2551.53	315.2 week*pg/mL Standard Deviation 79.39

SECONDARY outcome

Timeframe: Up to Week 12

An adverse event (AE) was defined as any untoward medical occurrence in a subject who is administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment. A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Number of participants with at least one AE and SAE were reported.

Outcome measures

Outcome measures
Measure	Peginterferon Alfa-2a + Ribavirin n=187 Participants Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=190 Participants Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Number of Participants With Adverse Events and Serious Adverse Events Any AE	185 participants	187 participants
Number of Participants With Adverse Events and Serious Adverse Events Any SAE	5 participants	2 participants

SECONDARY outcome

Timeframe: Baseline, Weeks 1, 4,8, and 12

Population: The ITT Population included all participants who were randomized and received at least one dose of study medication (PEG-IFN or ribavirin). This outcome measure was not analyzed as no data were collected for any of the participants in this study.

The determination of evolution of HCV quasispecies in participants was planned through analyzing viral sequences in serum samples drawn at baseline and at Weeks 1, 4, 8, and 12 if HCV RNA tests were positive and if the levels were sufficient to do the analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to Week 8

The estimation of weekly AUC for IFN concentrations for Pegasys and PEG-Intron was planned through population pharmacokinetic modeling. A population pharmacokinetic method deals with modelling in a cohort which has many participants (usually more than 40). The estimation of weekly AUC for IFN concentrations for Pegasys and PEG-Intron was planned to be studied in the population rather than the individuals in Peginterferon alfa-2a + Ribavirin and Peginterferon alfa-2b + Ribavirin groups.

Outcome measures

Outcome data not reported

Adverse Events

Peginterferon Alfa-2a + Ribavirin

Serious events: 14 serious events

Other events: 184 other events

Deaths: 0 deaths

Peginterferon Alfa-2b + Ribavirin

Serious events: 16 serious events

Other events: 186 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights
Publication restrictions are in place

Restriction type: OTHER

Measure	Peginterferon Alfa-2a + Ribavirin n=187 participants at risk Participants received Peginterferon alfa-2a at a dosage of 180 μg SC once a week plus Ribavirin 1000 or 1200 mg/day, orally (\< or \>/= 75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.	Peginterferon Alfa-2b + Ribavirin n=190 participants at risk Participants received Peginterferon alfa-2b at a dosage of 1.5 μg/kg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily during the randomized treatment period for 12 weeks. Participants who completed the randomized treatment period of 12 weeks and wished to continue therapy were given Peginterferon alfa-2a 180 μg SC once weekly plus Ribavirin 1000 or 1200 mg/day orally (\< or \>/=75 kg body weight, respectively) twice daily for an additional 36 weeks to complete a full 48-week treatment course. After treatment completion, participants were followed-up for safety for 24 weeks.
Gastrointestinal disorders Colitis ischaemic	1.1% 2/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.00% 0/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Gastrointestinal disorders Haematemesis	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Gastrointestinal disorders Nausea	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	1.1% 2/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Gastrointestinal disorders Vomiting	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	1.1% 2/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Gastrointestinal disorders Abdominal pain upper	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.00% 0/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Gastrointestinal disorders Pancreatitis	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
General disorders Chest pain	1.1% 2/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
General disorders Pelvic mass	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Infections and infestations Pneumonia	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Infections and infestations Gastroenteritis	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.00% 0/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Infections and infestations Viral rash	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.00% 0/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Infections and infestations Appendicitis	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Nervous system disorders Syncope	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	1.6% 3/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Nervous system disorders Hemiparesis	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.00% 0/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Psychiatric disorders Suicidal ideation	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Psychiatric disorders Mania	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Psychiatric disorders Psychotic disorder	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Cardiac disorders Tachycardia	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.00% 0/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Cardiac disorders Cardiomyopathy	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	1.1% 2/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Blood and lymphatic system disorders Anaemia	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.00% 0/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Endocrine disorders Hypothyroidism	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.00% 0/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Hepatobiliary disorders Cholecystitis	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Injury, poisoning and procedural complications Limb injury	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.00% 0/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.53% 1/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.
Vascular disorders Peripheral ischaemia	0.53% 1/187 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.	0.00% 0/190 • Up to Week 72 The adverse events were reported in safety population (187 and 190 participants in Peginterferon Alfa-2a + Ribavirin and Peginterferon Alfa-2b + Ribavirin respectively). The non-serious AEs were reported only till Week 12.