Trial Outcomes & Findings for VX-950-C211 - A Dosing Regimen Study (Twice Daily Versus Every 8 Hours) of Telaprevir in Treatment-naïve Participants With Genotype 1 Chronic Hepatitis C Virus Infection (NCT NCT01241760)

Last Updated: 2014-06-04

Results Overview

The table below shows the percentage of participants achieving Sustained Virologic Response 12 weeks after last planned dose of study medication (SVR12 planned). SVR was defined as having Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 international units/milliliter (IU/mL).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

744 participants

Primary outcome timeframe

End of trial, 12 weeks after last planned dose

Results posted on

2014-06-04

Participant Flow

This study evaluated the effectiveness of telaprevir administered twice daily versus every 8 hours in combination with pegylated interferon and ribavirin in treatment-naïve participants with chronic HCV genotype 1 infection.

The study was conducted between 15 November 2010 and 02 August 2012 and recruited participants from 125 study centers in 14 countries worldwide. 744 participants were initially enrolled and 740 out of them randomly allocated to the 2 treatment arms.

Participant milestones

Participant milestones
Measure	T12(q8h)/PR Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.
Overall Study STARTED	371	369
Overall Study COMPLETED	337	329
Overall Study NOT COMPLETED	34	40

Reasons for withdrawal

Reasons for withdrawal
Measure	T12(q8h)/PR Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	18	22
Overall Study Withdrawal by Subject	13	13
Overall Study Switch To Commercially Available Medicat	1	4
Overall Study Other	1	1

Baseline Characteristics

VX-950-C211 - A Dosing Regimen Study (Twice Daily Versus Every 8 Hours) of Telaprevir in Treatment-naïve Participants With Genotype 1 Chronic Hepatitis C Virus Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	T12(q8h)/PR n=371 Participants Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=369 Participants Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	Total n=740 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	351 Participants n=5 Participants	362 Participants n=7 Participants	713 Participants n=5 Participants
Age, Categorical >=65 years	17 Participants n=5 Participants	7 Participants n=7 Participants	24 Participants n=5 Participants
Age, Continuous	48 years n=5 Participants	47.5 years n=7 Participants	47.7 years n=5 Participants
Sex: Female, Male Female	136 Participants n=5 Participants	160 Participants n=7 Participants	296 Participants n=5 Participants
Sex: Female, Male Male	235 Participants n=5 Participants	209 Participants n=7 Participants	444 Participants n=5 Participants
Region of Enrollment Europe	192 participants n=5 Participants	179 participants n=7 Participants	371 participants n=5 Participants
Region of Enrollment North-America	126 participants n=5 Participants	137 participants n=7 Participants	263 participants n=5 Participants
Region of Enrollment Australia	28 participants n=5 Participants	28 participants n=7 Participants	56 participants n=5 Participants
Region of Enrollment Mexico	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Brazil	20 participants n=5 Participants	21 participants n=7 Participants	41 participants n=5 Participants

PRIMARY outcome

Timeframe: End of trial, 12 weeks after last planned dose

Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	T12(q8h)/PR n=371 Participants Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=369 Participants Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Drugs (SVR12 Planned)	72.8 percentage of participants with response	74.3 percentage of participants with response

SECONDARY outcome

Timeframe: End of trial, 24 weeks after last planned dose

Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.

The table below shows the percentage of participants achieving SVR 24 weeks after the last planned dose of study medication. SVR was defined as having Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 international units/milliliter (IU/mL). The response for T12(b.i.d)/PR group is higher than that after 12 weeks because HCV RNA data for two participants were missing for SVR assessment at that time. Consequently, by definition of SVR12, they were counted as not having achieved SVR12.

Outcome measures

Outcome measures
Measure	T12(q8h)/PR n=371 Participants Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=369 Participants Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.
Percentage of Participants With Sustained Virologic Response 24 Weeks After the Last Planned Dose of Study Drugs (SVR24 Planned)	72.8 percentage of participants with response	74.8 percentage of participants with response

SECONDARY outcome

Timeframe: End of trial, 72 weeks after the start of study medication

Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.

The table below shows the percentage of participants achieving SVR 72 weeks after the start of study medication (SVR72 planned). SVR was defined as having plasma Hepatitis C Virus (HCV) ribonucleic acid (RNA) levels less than 25 IU/mL, target not detected, at end of treatment and up to 72 weeks after start of study medication (i.e., no confirmed detectable HCV RNA in between).

Outcome measures

Outcome measures
Measure	T12(q8h)/PR n=371 Participants Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=369 Participants Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.
Percentage of Participants With Sustained Virologic Response 72 Weeks After the Start of Study Medication (SVR72 Planned)	69.0 percentage of participants with response	70.2 percentage of participants with response

SECONDARY outcome

Timeframe: Baseline, Week 4 and Week 4+12.

Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.

The table below shows the percentage of participants with undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels, which means less than 25 IU/ml, target not detected, at different time points during the study.

Outcome measures

Outcome measures
Measure	T12(q8h)/PR n=371 Participants Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=369 Participants Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.
Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. Baseline	0 percentage of participants with response	0 percentage of participants with response
Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. at Week 4	67.4 percentage of participants with response	69.4 percentage of participants with response
Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected, at Different Time Points. at Week 4 and Week 12	63.1 percentage of participants with response	66.1 percentage of participants with response

SECONDARY outcome

Timeframe: Week 4, 12, 24, 32, 40

Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.

The table below shows the percentage of participants who met a stopping rule, defined as having a hepatitis C virus (HCV) ribonucleic acid (RNA) value at Week 4 \>1000 IU/mL and at Weeks 12, 24, 32 and 40 ≥25 IU/mL.

Outcome measures

Outcome measures
Measure	T12(q8h)/PR n=371 Participants Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=369 Participants Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.
Percentage of Participants With On-treatment Virologic Failure Which Required Them to Permanently Discontinue All Study Drugs	9.7 percentage of participants	10.3 percentage of participants

SECONDARY outcome

Timeframe: During Follow-Up (24 weeks after the last dose of study drug)

Population: The analysis was performed on subjects with HCV RNA \<25 IU/mL at the planned end of treatment, which included all randomized participants who received at least one dose of study drug and had data at the follow-up visit performed 24 weeks after the last dose of study drug.

The table below shows the percentage of participants who relapsed (ie, those having confirmed detectable hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] during the 12-week follow-up period after previous HCV RNA \<25 IU/mL, target not detected, at end of treatment).

Outcome measures

Outcome measures
Measure	T12(q8h)/PR n=293 Participants Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=300 Participants Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.
Percentage of Participants Who Relapsed During Follow-up Period	7.2 percentage of participants	7.7 percentage of participants

SECONDARY outcome

Timeframe: End of trial, 12 weeks after the last planned dose

Population: All analyses were performed on the full analysis (FA) set, which was defined as all randomized subjects who received at least one dose of study drug.

The table below shows the effect of interleukin 28B (IL28B) gene's subtype (CC, CT or TT genotype) on the primary outcome measure: SVR12 planned.

Outcome measures

Outcome measures
Measure	T12(q8h)/PR n=371 Participants Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=369 Participants Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.
Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) CC genotype (n = 108; n = 103)	86.8 percentage of participants with response	92.4 percentage of participants with response
Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) CT genotype (n = 207; n = 207)	67.8 percentage of participants with response	67.5 percentage of participants with response
Percentage of Participants of Each IL28B Genotype Achieving Sustained Virologic Response 12 Weeks After the Last Planned Dose of Study Medication (SVR12 Planned) TT genotype (n = 56; n = 59)	64.9 percentage of participants with response	65.5 percentage of participants with response

Adverse Events

T12(q8h)/PR

Serious events: 35 serious events

Other events: 359 other events

Deaths: 0 deaths

T12(b.i.d.)/PR

Serious events: 28 serious events

Other events: 358 other events

Deaths: 0 deaths

Total

Serious events: 63 serious events

Other events: 717 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Compound Development Team Leader

Janssen Infectious Diseases BVBA

Phone: 32 14 64 13 70

Results disclosure agreements

Principal investigator is a sponsor employee If the PI (Investigator) wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	T12(q8h)/PR n=371 participants at risk Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=369 participants at risk Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	Total n=740 participants at risk All
Blood and lymphatic system disorders Anaemia	3.8% 14/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	3.5% 13/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	3.6% 27/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Blood and lymphatic system disorders Thrombocytopenia	0.54% 2/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 2/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Blood and lymphatic system disorders Leukopenia	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Blood and lymphatic system disorders Neutropenia	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Blood and lymphatic system disorders Pancytopenia	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 2/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Abscess	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Cellulitis	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Escherichia sepsis	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Sinusitis	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Subcutaneous abscess	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Urinary tract infection	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 2/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Infections and infestations Pneumonia	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Asthenia	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 2/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Chest discomfort	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Chest pain	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Fatigue	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Pyrexia	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Non-cardiac chest pain	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Drug eruption	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Rash	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.54% 2/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.41% 3/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Rash generalised	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Urticaria	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Drug rash with eosinophilia and systemic symptoms	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Syncope	0.81% 3/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.54% 2/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.68% 5/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Facial palsy	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Hemiparesis	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Hypoaesthesia	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Myoclonus	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Paraesthesia	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Reproductive system and breast disorders Menorrhagia	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Reproductive system and breast disorders Postmenopausal haemorrhage	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Reproductive system and breast disorders Vaginal haemorrhage	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Metabolism and nutrition disorders Dehydration	0.54% 2/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 2/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Diarrhoea	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 2/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Haematochezia	0.00% 0/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.27% 1/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Hepatobiliary disorders Hyperbilirubinaemia	0.27% 1/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.00% 0/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	0.14% 1/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.

Other adverse events
Measure	T12(q8h)/PR n=371 participants at risk Telaprevir 750 mg (2 oral tablets) every 8 hours for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	T12(b.i.d.)/PR n=369 participants at risk Telaprevir 1125 mg (3 oral tablets) twice a day (every 10-14 hours) for 12 weeks, in combination with pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day for 24 or 48 weeks depending on the treatment response at week 4.	Total n=740 participants at risk All
General disorders Fatigue	48.0% 178/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	46.9% 173/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	47.4% 351/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Pyrexia	21.0% 78/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	16.8% 62/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	18.9% 140/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Asthenia	19.4% 72/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	17.6% 65/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	18.5% 137/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Influenza like illness	16.2% 60/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	20.3% 75/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	18.2% 135/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Chills	11.6% 43/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.0% 22/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.8% 65/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
General disorders Injection site reaction	6.7% 25/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.2% 23/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.5% 48/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Pruritus	42.6% 158/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	42.8% 158/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	42.7% 316/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Rash	35.8% 133/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	35.0% 129/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	35.4% 262/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Dry skin	9.4% 35/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	11.7% 43/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.5% 78/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Skin and subcutaneous tissue disorders Erythema	5.9% 22/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.4% 20/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.7% 42/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Nausea	38.5% 143/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	35.0% 129/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	36.8% 272/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Diarrhoea	19.1% 71/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	13.3% 49/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	16.2% 120/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Anal pruritus	11.6% 43/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.1% 30/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	9.9% 73/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Vomiting	11.1% 41/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.3% 38/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.7% 79/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Anorectal discomfort	9.7% 36/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.6% 39/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.1% 75/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Haemorrhoids	8.9% 33/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.0% 26/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.0% 59/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Dry mouth	6.2% 23/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.5% 24/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.4% 47/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Dyspepsia	5.9% 22/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.1% 15/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.0% 37/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Proctalgia	5.7% 21/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.9% 18/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.3% 39/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Gastrointestinal disorders Abdominal pain	5.1% 19/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	2.7% 10/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	3.9% 29/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Blood and lymphatic system disorders Anaemia	39.9% 148/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	42.0% 155/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	40.9% 303/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Blood and lymphatic system disorders Neutropenia	8.1% 30/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	9.8% 36/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.9% 66/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Blood and lymphatic system disorders Thrombocytopenia	8.1% 30/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.9% 29/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.0% 59/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Headache	29.1% 108/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	23.6% 87/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	26.4% 195/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Dysgeusia	12.4% 46/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	9.8% 36/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	11.1% 82/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Nervous system disorders Dizziness	8.1% 30/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	11.1% 41/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	9.6% 71/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Psychiatric disorders Insomnia	18.3% 68/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	18.7% 69/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	18.5% 137/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Psychiatric disorders Mood altered	12.7% 47/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.0% 37/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	11.4% 84/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Psychiatric disorders Depression	9.7% 36/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.3% 27/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.5% 63/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Psychiatric disorders Anxiety	5.4% 20/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	7.0% 26/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.2% 46/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.9% 44/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.6% 39/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	11.2% 83/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Respiratory, thoracic and mediastinal disorders Cough	9.4% 35/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	9.8% 36/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	9.6% 71/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.1% 19/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.6% 17/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	4.9% 36/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Musculoskeletal and connective tissue disorders Myalgia	11.1% 41/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.9% 33/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	10.0% 74/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 24/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.8% 25/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.6% 49/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Metabolism and nutrition disorders Anorexia	9.7% 36/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.1% 30/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	8.9% 66/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Metabolism and nutrition disorders Decreased appetite	5.1% 19/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	6.0% 22/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.5% 41/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.
Eye disorders Vision blurred	4.6% 17/371 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.4% 20/369 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.	5.0% 37/740 • Adverse event data were collected for the duration of study (12 weeks after the last dose). The total number of adverse events listed in the "Other (non-Serious) Adverse Events" table are based upon a cut-off of greater than or equal to 5 percent of patients experiencing the adverse event in any treatment arm.