Trial Outcomes & Findings for 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 (NCT NCT00882908)

NCT ID: NCT00882908

Last Updated: 2014-06-16

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 386 participants
• Primary outcome timeframe: Week 72
• Results posted on: 2014-06-16

Participant Flow

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.

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.

Participant milestones

Measure	TMC435 75 mg 12 Wks + PR 24/48 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.	TMC435 75 mg 24 Wks + PR 24/48 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.	TMC435 150 mg 12 Wks + PR 24/48 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.	TMC435 150 mg 24 Wks + PR 24/48 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.	Placebo 24 Wks + PR48 Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Study STARTED	78	75	77	79	77
Overall Study COMPLETED	75	69	70	72	71
Overall Study NOT COMPLETED	3	6	7	7	6

Reasons for withdrawal

Measure	TMC435 75 mg 12 Wks + PR 24/48 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.	TMC435 75 mg 24 Wks + PR 24/48 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.	TMC435 150 mg 12 Wks + PR 24/48 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.	TMC435 150 mg 24 Wks + PR 24/48 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.	Placebo 24 Wks + PR48 Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Overall Study Adverse Event	0	0	1	0	1
Overall Study Lost to Follow-up	3	5	3	1	2
Overall Study Protocol Violation	0	1	0	0	0
Overall Study Withdrawal by Subject	0	0	3	5	2
Overall Study Subject reached a virologic endpoint	0	0	0	0	1
Overall Study Study terminated in error	0	0	0	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.	Total n=386 Participants Total of all reporting groups
Age, Continuous	47 years n=5 Participants	46 years n=7 Participants	47 years n=5 Participants	47 years n=4 Participants	45 years n=21 Participants	46.5 years n=8 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	28 Participants n=7 Participants	34 Participants n=5 Participants	35 Participants n=4 Participants	38 Participants n=21 Participants	173 Participants n=8 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	47 Participants n=7 Participants	43 Participants n=5 Participants	44 Participants n=4 Participants	39 Participants n=21 Participants	213 Participants n=8 Participants
Region of Enrollment Asia Pacific	9 participants n=5 Participants	9 participants n=7 Participants	7 participants n=5 Participants	13 participants n=4 Participants	4 participants n=21 Participants	42 participants n=8 Participants
Region of Enrollment Europe	52 participants n=5 Participants	52 participants n=7 Participants	56 participants n=5 Participants	44 participants n=4 Participants	58 participants n=21 Participants	262 participants n=8 Participants
Region of Enrollment North-America	17 participants n=5 Participants	14 participants n=7 Participants	14 participants n=5 Participants	22 participants n=4 Participants	15 participants n=21 Participants	82 participants n=8 Participants

PRIMARY outcome

Timeframe: Week 72

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)	70.7 Percentage of participants	80.8 Percentage of participants	77.9 Percentage of participants	84.8 Percentage of participants	64.9 Percentage of participants

SECONDARY outcome

Timeframe: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

Population: 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.

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).

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
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 Week 2	30.7 Percentage of participants	39.7 Percentage of participants	23.4 Percentage of participants	39.2 Percentage of participants	2.6 Percentage of participants
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 Week 4	68.0 Percentage of participants	75.6 Percentage of participants	75.3 Percentage of participants	74.7 Percentage of participants	5.2 Percentage of participants
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 Week 8	90.7 Percentage of participants	87.2 Percentage of participants	92.2 Percentage of participants	93.7 Percentage of participants	26.0 Percentage of participants
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 Week 12	93.3 Percentage of participants	91.0 Percentage of participants	93.5 Percentage of participants	94.9 Percentage of participants	55.8 Percentage of participants
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 Week 24	93.3 Percentage of participants	92.3 Percentage of participants	84.4 Percentage of participants	87.3 Percentage of participants	77.9 Percentage of participants
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 Week 36	81.3 Percentage of participants	85.9 Percentage of participants	81.8 Percentage of participants	84.8 Percentage of participants	76.6 Percentage of participants
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 Week 48	77.3 Percentage of participants	79.5 Percentage of participants	79.2 Percentage of participants	82.3 Percentage of participants	74.0 Percentage of participants
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 Week 60	68.0 Percentage of participants	79.5 Percentage of participants	75.3 Percentage of participants	83.5 Percentage of participants	63.6 Percentage of participants
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 Week 72	70.7 Percentage of participants	79.5 Percentage of participants	77.9 Percentage of participants	82.3 Percentage of participants	64.9 Percentage of participants
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 EOT (up to Week 24 or 48)	97.3 Percentage of participants	92.3 Percentage of participants	92.2 Percentage of participants	93.7 Percentage of participants	79.2 Percentage of participants

SECONDARY outcome

Timeframe: Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

Population: 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.

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).

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
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 Week 2	66.7 Percentage of participants	65.4 Percentage of participants	75.3 Percentage of participants	78.5 Percentage of participants	5.2 Percentage of participants
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 Week 4	88.0 Percentage of participants	85.9 Percentage of participants	90.9 Percentage of participants	91.1 Percentage of participants	15.6 Percentage of participants
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 Week 8	94.7 Percentage of participants	93.6 Percentage of participants	93.5 Percentage of participants	93.7 Percentage of participants	49.4 Percentage of participants
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 Week 12	94.7 Percentage of participants	93.6 Percentage of participants	96.1 Percentage of participants	94.9 Percentage of participants	66.2 Percentage of participants
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 Week 24	93.3 Percentage of participants	92.3 Percentage of participants	84.4 Percentage of participants	89.9 Percentage of participants	80.5 Percentage of participants
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 Week 36	81.3 Percentage of participants	85.9 Percentage of participants	81.8 Percentage of participants	84.8 Percentage of participants	79.2 Percentage of participants
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 Week 48	77.3 Percentage of participants	79.5 Percentage of participants	79.2 Percentage of participants	82.3 Percentage of participants	75.3 Percentage of participants
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 Week 60	68.0 Percentage of participants	79.5 Percentage of participants	75.3 Percentage of participants	83.5 Percentage of participants	64.9 Percentage of participants
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 Week 72	70.7 Percentage of participants	79.5 Percentage of participants	77.9 Percentage of participants	83.5 Percentage of participants	64.9 Percentage of participants
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 EOT (up to Week 24 or 48)	97.3 Percentage of participants	93.6 Percentage of participants	92.2 Percentage of participants	96.2 Percentage of participants	83.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Weeks, 2, 4, 8, and 12

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
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 Week 2	98.7 Percentage of participants	93.6 Percentage of participants	97.4 Percentage of participants	98.7 Percentage of participants	40.3 Percentage of participants
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 Week 4	98.7 Percentage of participants	94.9 Percentage of participants	97.4 Percentage of participants	93.7 Percentage of participants	71.4 Percentage of participants
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 Week 8	97.3 Percentage of participants	97.4 Percentage of participants	97.4 Percentage of participants	94.9 Percentage of participants	84.4 Percentage of participants
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 Week 12	96.0 Percentage of participants	97.4 Percentage of participants	96.1 Percentage of participants	96.2 Percentage of participants	89.6 Percentage of participants

SECONDARY outcome

Timeframe: Week 48 or 72

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)	74.7 Percentage of participants	82.1 Percentage of participants	80.5 Percentage of participants	86.1 Percentage of participants	64.9 Percentage of participants

SECONDARY outcome

Timeframe: Week 4

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)	68.0 Percentage of participants	75.6 Percentage of participants	75.3 Percentage of participants	74.7 Percentage of participants	5.2 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (Day 1) and Week 12

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
The Percentage of Participants Achieving an Early Virologic Response (EVR)	96.0 Percentage of participants	97.4 Percentage of participants	96.1 Percentage of participants	96.2 Percentage of participants	89.6 Percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)	93.3 Percentage of participants	91.0 Percentage of participants	93.5 Percentage of participants	94.9 Percentage of participants	55.8 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 36 or 52

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)	76.0 Percentage of participants	83.3 Percentage of participants	80.5 Percentage of participants	86.1 Percentage of participants	66.2 Percentage of participants

SECONDARY outcome

Timeframe: Week 24 or 48

Population: 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.

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).

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Number of Participants With Viral Breakthrough	2 Participants	5 Participants	6 Participants	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to Week 72

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=78 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 Participants 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.	Placebo 24 Wks + PR48 n=77 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
The Number of Participants With Viral Relapse	14 Participants	8 Participants	6 Participants	6 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1) up to Week 24 or 48

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=45 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=43 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=48 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=43 Participants 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.	Placebo 24 Wks + PR48 n=179 Participants Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)	37 Participants	39 Participants	39 Participants	35 Participants	150 Participants

SECONDARY outcome

Timeframe: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

Population: 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.

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.

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=78 Participants 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.	Placebo 24 Wks + PR48 Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Plasma Concentrations of TMC435 Coh	213.6 ng/mL Interval 40.0 to 2124.0	240.9 ng/mL Interval 0.0 to 1927.0	1123.3 ng/mL Interval 91.0 to 13771.0	1176.7 ng/mL Interval 0.0 to 9875.0	—
Plasma Concentrations of TMC435 Css, av	374.0 ng/mL Interval 151.0 to 2385.0	413.6 ng/mL Interval 6.0 to 2091.0	1661.8 ng/mL Interval 123.0 to 15868.0	1501.6 ng/mL Interval 47.0 to 11648.0	—

SECONDARY outcome

Timeframe: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

Population: 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.

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).

Outcome measures

Measure	TMC435 75 mg 24 Wks + PR 24/48 n=75 Participants 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.	TMC435 75 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 Participants 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.	TMC435 150 mg 24 Wks + PR 24/48 n=78 Participants 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.	Placebo 24 Wks + PR48 Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435	8976.8 ng*h/mL Interval 3615.0 to 57243.0	9926.4 ng*h/mL Interval 138.0 to 50179.0	39884.0 ng*h/mL Interval 2948.0 to 380830.0	36038.8 ng*h/mL Interval 1134.0 to 279550.0	—

Adverse Events

TMC435 75 mg 12 Wks + PR 24/48

Serious events: 9 serious events

Other events: 76 other events

Deaths: 0 deaths

TMC435 75 mg 24 Wks + PR 24/48

Serious events: 4 serious events

Other events: 75 other events

Deaths: 0 deaths

TMC435 150 mg 12 Wks + PR 24/48

Serious events: 4 serious events

Other events: 74 other events

Deaths: 0 deaths

TMC435 150 mg 24 Wks + PR 24/48

Serious events: 3 serious events

Other events: 77 other events

Deaths: 0 deaths

Placebo 24 Wks + PR48

Serious events: 10 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Measure	TMC435 75 mg 12 Wks + PR 24/48 n=78 participants at risk 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.	TMC435 75 mg 24 Wks + PR 24/48 n=75 participants at risk 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 participants at risk 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 participants at risk 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.	Placebo 24 Wks + PR48 n=77 participants at risk Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour benign	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian neoplasm	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Endocrine disorders Hyperthyroidism	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Eye disorders Ocular vasculitis	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Malaise	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Asthenia	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Hepatobiliary disorders Cholecystitis	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Injury, poisoning and procedural complications Post procedural bile leak	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Nervous system disorders Headache	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Psychiatric disorders Depression	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Incision site cellulitis	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Necrotising fasciitis	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Perihepatic abscess	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Pneumonia pneumococcal	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Upper respiratory tract infection	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Appendicitis	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Subcutaneous abscess	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Vulval abscess	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Colitis	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Nausea	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Vomiting	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Metabolism and nutrition disorders Malnutrition	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Metabolism and nutrition disorders Type 1 diabetes mellitus	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Musculoskeletal and connective tissue disorders Spinal disorder	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Cutaneous vasculitis	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Vascular disorders Hypertension	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Cardiac disorders Myocardial infarction	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Cardiac disorders Myopericarditis	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.

Other adverse events

Measure	TMC435 75 mg 12 Wks + PR 24/48 n=78 participants at risk 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.	TMC435 75 mg 24 Wks + PR 24/48 n=75 participants at risk 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.	TMC435 150 mg 12 Wks + PR 24/48 n=77 participants at risk 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.	TMC435 150 mg 24 Wks + PR 24/48 n=79 participants at risk 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.	Placebo 24 Wks + PR48 n=77 participants at risk Participants received Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Psychiatric disorders Insomnia	24.4% 19/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	18.7% 14/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	29.9% 23/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	16.5% 13/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	29.9% 23/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Psychiatric disorders Depression	10.3% 8/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.3% 4/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	11.7% 9/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	13.9% 11/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	18.2% 14/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Psychiatric disorders Sleep disorder	10.3% 8/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	4.0% 3/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	8.9% 7/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Psychiatric disorders Mood altered	5.1% 4/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.7% 5/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	10.1% 8/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	9.1% 7/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Psychiatric disorders Depressed mood	5.1% 4/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.3% 4/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.6% 6/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Psychiatric disorders Anxiety	6.4% 5/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.7% 2/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Psychiatric disorders Mood swings	5.1% 4/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.3% 5/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Musculoskeletal and connective tissue disorders Myalgia	21.8% 17/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	16.0% 12/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	20.8% 16/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	12.7% 10/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	22.1% 17/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Musculoskeletal and connective tissue disorders Arthralgia	14.1% 11/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	16.0% 12/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	18.2% 14/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	20.3% 16/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	14.3% 11/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Musculoskeletal and connective tissue disorders Back pain	6.4% 5/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	10.7% 8/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	13.0% 10/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	8.9% 7/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	9.1% 7/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Musculoskeletal and connective tissue disorders Muscle spasms	5.1% 4/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.7% 2/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.3% 4/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.8% 3/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.8% 3/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Fatigue	33.3% 26/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	46.7% 35/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	41.6% 32/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	48.1% 38/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	48.1% 37/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Influenza like illness	26.9% 21/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	42.7% 32/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	23.4% 18/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	34.2% 27/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	37.7% 29/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Pyrexia	23.1% 18/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	20.0% 15/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	19.5% 15/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	20.3% 16/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	16.9% 13/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Asthenia	25.6% 20/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	16.0% 12/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	23.4% 18/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	16.5% 13/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	20.8% 16/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Irritability	12.8% 10/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	9.3% 7/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	18.2% 14/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	13.9% 11/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	10.4% 8/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Chills	5.1% 4/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	10.7% 8/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	8.9% 7/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	10.4% 8/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Injection site erythema	5.1% 4/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	10.7% 8/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	8.9% 7/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Injection site reaction	6.4% 5/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.3% 4/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.5% 2/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
General disorders Pain	7.7% 6/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.7% 2/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Pruritus	32.1% 25/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	22.7% 17/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	39.0% 30/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	30.4% 24/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	45.5% 35/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Rash	26.9% 21/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	13.3% 10/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	20.8% 16/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	22.8% 18/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	23.4% 18/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Dry skin	15.4% 12/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	16.0% 12/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	22.1% 17/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	27.8% 22/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	18.2% 14/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Alopecia	25.6% 20/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	14.7% 11/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	14.3% 11/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	13.9% 11/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	20.8% 16/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Erythema	3.8% 3/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.7% 2/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.3% 5/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Eczema	9.0% 7/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.8% 3/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Pruritus generalised	3.8% 3/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.7% 2/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.6% 6/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Night sweats	7.7% 6/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.5% 2/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Dermatitis	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.3% 4/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	4.0% 3/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.8% 3/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Nervous system disorders Headache	52.6% 41/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	45.3% 34/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	45.5% 35/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	40.5% 32/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	51.9% 40/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Nervous system disorders Dizziness	12.8% 10/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	4.0% 3/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	15.2% 12/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Nervous system disorders Disturbance in attention	6.4% 5/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	4.0% 3/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Nervous system disorders Dysgeusia	7.7% 6/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Nervous system disorders Paraesthesia	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Nervous system disorders Syncope	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.7% 2/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Nervous system disorders Migraine	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Nervous system disorders Hypoaesthesia	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Nausea	33.3% 26/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	21.3% 16/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	26.0% 20/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	30.4% 24/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	27.3% 21/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Diarrhoea	15.4% 12/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	18.7% 14/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	14.3% 11/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	12.7% 10/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	15.6% 12/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Vomiting	6.4% 5/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	4.0% 3/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	10.1% 8/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Dry mouth	6.4% 5/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	9.3% 7/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.6% 6/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	9.1% 7/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Abdominal pain upper	6.4% 5/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.3% 4/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Dyspepsia	5.1% 4/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.7% 5/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.6% 6/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Constipation	7.7% 6/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	9.1% 7/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.5% 2/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Abdominal pain	5.1% 4/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	4.0% 3/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.8% 3/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Gastrointestinal disorders Aphthous stomatitis	2.6% 2/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.5% 2/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Respiratory, thoracic and mediastinal disorders Cough	23.1% 18/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	12.0% 9/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	15.6% 12/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	16.5% 13/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	19.5% 15/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.4% 12/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	10.7% 8/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	9.1% 7/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.6% 6/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	7.7% 6/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	12.0% 9/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	13.0% 10/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.3% 5/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	9.1% 7/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.4% 5/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	4.0% 3/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	10.4% 8/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Blood and lymphatic system disorders Neutropenia	19.2% 15/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	30.7% 23/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	24.7% 19/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	22.8% 18/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	20.8% 16/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Blood and lymphatic system disorders Anaemia	19.2% 15/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	21.3% 16/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	22.1% 17/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	19.0% 15/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	20.8% 16/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Blood and lymphatic system disorders Leukopenia	2.6% 2/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.6% 6/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Nasopharyngitis	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.7% 5/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Influenza	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.7% 5/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.8% 3/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Urinary tract infection	2.6% 2/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.7% 2/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.3% 5/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Infections and infestations Sinusitis	5.1% 4/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.5% 2/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Investigations Weight decreased	9.0% 7/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	4.0% 3/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.6% 6/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Investigations Neutrophil count decreased	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.7% 5/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Investigations Blood bilirubin increased	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.3% 5/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Investigations Alanine aminotransferase increased	3.8% 3/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.3% 5/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Investigations Aspartate aminotransferase increased	2.6% 2/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.6% 6/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Investigations Gamma-glutamyltransferase increased	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Metabolism and nutrition disorders Anorexia	12.8% 10/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	16.0% 12/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	14.3% 11/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	11.4% 9/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	14.3% 11/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Metabolism and nutrition disorders Decreased appetite	7.7% 6/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	4.0% 3/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	7.8% 6/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Eye disorders Dry eye	3.8% 3/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.7% 2/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Eye disorders Vision blurred	3.8% 3/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.8% 3/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Ear and labyrinth disorders Vertigo	6.4% 5/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	3.9% 3/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.2% 4/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Vascular disorders Hot flush	1.3% 1/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.3% 5/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Vascular disorders Hypertension	0.00% 0/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	5.1% 4/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Hepatobiliary disorders Hyperbilirubinaemia	2.6% 2/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	0.00% 0/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.5% 2/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	2.6% 2/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.
Endocrine disorders Hypothyroidism	7.7% 6/78 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/75 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	1.3% 1/79 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.	6.5% 5/77 • 72 weeks All participants who received at least one dose of investigational medication included in safety analysis.

Additional Information

Global Clinical Development Manager

Jan-Cil France

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60