Trial Outcomes & Findings for Phase III Trial of BI 201335 (Faldaprevir) in Treatment Naive (TN) and Relapser Hepatitis C Virus (HCV)-Human Immunodeficiency Virus (HIV) Coinfected Patients (STARTverso 4) (NCT NCT01399619)

Last Updated: 2016-08-29

Results Overview

Percentage of participants with sustained Virological Response SVR12: Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) level \<25 IU/mL, undetected 12 weeks after the planned end of treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

310 participants

Primary outcome timeframe

60 weeks

Results posted on

2016-08-29

Participant Flow

Participant milestones

Participant milestones
Measure	Faldaprevir 120mg -24W Faldaprevir (BI 201335) 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -12W Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg-24W Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue Faldaprevir to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240 mg -NR (Prior to Re-randomization at Week 12) Patients initially assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at WK 12.
Overall Study STARTED	123	84	86	17
Overall Study COMPLETED	98	84	74	0
Overall Study NOT COMPLETED	25	0	12	17

Reasons for withdrawal

Reasons for withdrawal
Measure	Faldaprevir 120mg -24W Faldaprevir (BI 201335) 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg-24W Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue Faldaprevir to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240 mg -NR (Prior to Re-randomization at Week 12) Patients initially assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at WK 12.
Overall Study Adverse Event	10	4	10
Overall Study Lack of Efficacy	9	5	0
Overall Study Withdrawal by Subject	6	3	4
Overall Study Protocol Violation	0	0	1
Overall Study Not treated	0	0	2

Baseline Characteristics

Phase III Trial of BI 201335 (Faldaprevir) in Treatment Naive (TN) and Relapser Hepatitis C Virus (HCV)-Human Immunodeficiency Virus (HIV) Coinfected Patients (STARTverso 4)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg QD combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants patient to receive Faldaprevir 240 mg once a day for 12 or 24 weeks and PegIFN/RBV for 24 or 48 weeks + patients who received Faldaprevir 240 mg and discontinued prior to week 12.	Total n=308 Participants Total of all reporting groups
Age, Continuous	47.6 years STANDARD_DEVIATION 7.63 • n=5 Participants	46.5 years STANDARD_DEVIATION 8.36 • n=7 Participants	46.9 years STANDARD_DEVIATION 8.08 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	40 Participants n=7 Participants	60 Participants n=5 Participants
Sex: Female, Male Male	103 Participants n=5 Participants	145 Participants n=7 Participants	248 Participants n=5 Participants

PRIMARY outcome

Timeframe: 60 weeks

Population: FAS

Percentage of participants with sustained Virological Response SVR12: Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) level \<25 IU/mL, undetected 12 weeks after the planned end of treatment.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
Sustained Virological Response (SVR12)	70.7 percentage of participants Interval 62.7 to 78.8	78.6 percentage of participants Interval 69.8 to 87.3	76.7 percentage of participants Interval 67.8 to 85.7	72.4 percentage of participants Interval 66.0 to 78.9	71.8 percentage of participants Interval 66.7 to 76.8

SECONDARY outcome

Timeframe: 72 weeks

Population: FAS

Percentage of participants with virological response 24 weeks post treatment (SVR24): Plasma HCV RNA level\<25IU/mL (undetected) 24 weeks after the planned end of treatment.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
Virological Response 24 Weeks Post Treatment (SVR24)	69.9 percentage of participants Interval 61.8 to 78.0	78.6 percentage of participants Interval 69.8 to 87.3	74.4 percentage of participants Interval 65.2 to 83.6	71.4 percentage of participants Interval 64.8 to 77.9	70.8 percentage of participants Interval 65.7 to 75.9

SECONDARY outcome

Timeframe: Week 4, week 8 and week 60

Population: FAS

Early Treatment Success (ETS): Plasma HCV RNA level\<25 IU/mL (detected or undetected) at Week 4 and HCV RNA\< 25 IU/mL, undetected at Week 8

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
Early Treatment Success (ETS) number of subjects with ETS =yes	95 participants	70 participants	73 participants	150 participants	245 participants
Early Treatment Success (ETS) number of subjects with SVR12 among ETS=yes group	83 participants	62 participants	63 participants	127 participants	210 participants

SECONDARY outcome

Timeframe: 48 weeks

Population: FAS

The number of participants with Alanine Aminotransferase (ALT) normalisation at End of Treatment (EoT) when SVR12=yes. BL stands for baseline.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment (EoT) When SVR12=Yes SVR12=yes, No BL or EoT data	0 participants	0 participants	0 participants	1 participants	1 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment (EoT) When SVR12=Yes SVR12=yes	87 participants	66 participants	66 participants	134 participants	221 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment (EoT) When SVR12=Yes SVR12=yes, BL normal to EOT normal	29 participants	16 participants	26 participants	43 participants	72 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment (EoT) When SVR12=Yes SVR12=yes, BL elevated to EOT normal	45 participants	34 participants	32 participants	66 participants	111 participants

SECONDARY outcome

Timeframe: 48 weeks

Population: FAS

The number of participants with Alanine Aminotransferase (ALT) normalisation: ALT in normal range at End of Treatment when SVR12=no. BL stands for baseline.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment When SVR12=no SVR12=no, BL elevated to EoT normal	12 participants	8 participants	9 participants	21 participants	33 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment When SVR12=no SVR12=no, no BL or EoT data available	2 participants	0 participants	0 participants	0 participants	2 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment When SVR12=no SVR12=no, BL normal to EoT normal	18 participants	5 participants	5 participants	18 participants	36 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at End of Treatment When SVR12=no SVR12=no	36 participants	18 participants	20 participants	51 participants	87 participants

SECONDARY outcome

Timeframe: 60 weeks

Population: FAS

The number of participants with ALT in normal range at post treatment (SVR12 Visit) when SVR12=yes. BL = baseline.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=Yes SVR12=yes	87 participants	66 participants	66 participants	134 participants	221 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=Yes SVR12=yes, BL normal to SVR12 normal	28 participants	17 participants	26 participants	45 participants	73 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=Yes SVR12=yes, BL elevated to SVR12 normal	52 participants	46 participants	35 participants	81 participants	133 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=Yes SVR12=yes, no ALT data available at SVR12 visit	4 participants	0 participants	1 participants	1 participants	5 participants

SECONDARY outcome

Timeframe: 60 weeks

Population: FAS

The number of participants with ALT in normal range at post treatment (SVR12 Visit) when SVR12=no. BL = baseline.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=no SVR12=no	36 participants	18 participants	20 participants	51 participants	87 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=no SVR12=no, BL elevated to SVR12 normal	1 participants	6 participants	3 participants	9 participants	10 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=no SVR12=no, no ALT data available at SVR12 visit	16 participants	4 participants	6 participants	20 participants	36 participants
The Number of Participants With Alanine Aminotransferase (ALT) Normalisation at Post Treatment When SVR12=no SVR12=no, BL normal to SVR12 normal	8 participants	1 participants	3 participants	6 participants	14 participants

SECONDARY outcome

Timeframe: 48 weeks

Population: FAS

The number of participants with Aspartate Aminotransferase (AST) normalisation at End of Treatment when SVR12=yes. BL = baseline.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=Yes SVR12=yes	87 participants	66 participants	66 participants	134 participants	221 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=Yes SVR12=yes, BL normal to EoT normal	41 participants	25 participants	28 participants	54 participants	95 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=Yes SVR12=yes, BL elevated to EoT normal	32 participants	25 participants	27 participants	52 participants	84 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=Yes SVR12=yes, no BL or EoT data available	0 participants	0 participants	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: 48 weeks

Population: FAS

The number of participants with Aspartate Aminotransferase (AST) normalisation at End of Treatment when SVR12=no. BL = baseline.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=no SVR12=no, no BL or EoT data available	2 participants	0 participants	0 participants	0 participants	2 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=no SVR12=no	36 participants	18 participants	20 participants	51 participants	87 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=no SVR12=no, BL normal to EoT normal	14 participants	6 participants	7 participants	19 participants	33 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at End of Treatment When SVR12=no SVR12=no, BL elevated to EoT normal	12 participants	6 participants	8 participants	19 participants	31 participants

SECONDARY outcome

Timeframe: 60 weeks

Population: FAS

The number of participants with AST in normal range at Post Treatment (SVR12 Visit) when SVR12=yes. BL = baseline.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=Yes SVR12=yes	87 participants	66 participants	66 participants	134 participants	221 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=Yes SVR12=yes, BL normal to SVR12 normal	41 participants	27 participants	28 participants	57 participants	98 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=Yes SVR12=yes, BL elevated to SVR12 normal	36 participants	36 participants	33 participants	69 participants	105 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=Yes SVR12=yes, no AST data available at SVR12 visit	4 participants	0 participants	1 participants	1 participants	5 participants

SECONDARY outcome

Timeframe: 60 weeks

Population: FAS

The number of participants with AST in normal range at Post Treatment (SVR12 Visit) when SVR12=no. BL = baseline.

Outcome measures

Outcome measures
Measure	Faldaprevir 120mg - 24W n=123 Participants Faldaprevir 120 mg once a day (QD) combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 Participants Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue BI 201335 to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 Participants Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.	Faldaprevir - Total n=308 Participants Total subjects who were treated with Faldaprevir.
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=no SVR12=no, BL normal to SVR12 normal	6 participants	4 participants	6 participants	13 participants	19 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=no SVR12=no, BL elevated to SVR12 normal	2 participants	3 participants	0 participants	3 participants	5 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=no SVR12=no	36 participants	18 participants	20 participants	51 participants	87 participants
The Number of Participants With Aspartate Aminotransferase (AST) Normalisation at Post Treatment When SVR12=no SVR12=no, no AST data available at SVR12 visit	16 participants	4 participants	6 participants	20 participants	36 participants

Adverse Events

Faldaprevir 120mg - 24W

Serious events: 17 serious events

Other events: 116 other events

Deaths: 0 deaths

Faldaprevir 240mg - 12W

Serious events: 5 serious events

Other events: 80 other events

Deaths: 0 deaths

Faldaprevir 240mg - 24W

Serious events: 5 serious events

Other events: 84 other events

Deaths: 0 deaths

Faldaprevir 240mg -T

Serious events: 15 serious events

Other events: 178 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Faldaprevir 120mg - 24W n=123 participants at risk Faldaprevir 120 mg QD combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 participants at risk Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 participants at risk Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue Faldaprevir to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 participants at risk Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.
Blood and lymphatic system disorders Anaemia	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.1% 2/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Cardiac disorders Acute coronary syndrome	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Cardiac disorders Acute myocardial infarction	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Endocrine disorders Hyperthyroidism	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Abdominal pain	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.1% 2/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Diarrhoea	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Enterovesical fistula	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Nausea	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Vomiting	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
General disorders Asthenia	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
General disorders Pyrexia	2.4% 3/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Hepatobiliary disorders Cholecystitis	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Immune system disorders Sarcoidosis	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Appendicitis	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Diverticulitis	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Escherichia urinary tract infection	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Gastroenteritis	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Gastroenteritis viral	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Infected cyst	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Leishmaniasis	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Neurosyphilis	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Pneumonia	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Pneumonia bacterial	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Pulmonary tuberculosis	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Sepsis	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Urosepsis	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Metabolism and nutrition disorders Decreased appetite	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Metabolism and nutrition disorders Dehydration	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Nervous system disorders Epilepsy	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.2% 1/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Renal and urinary disorders Nephrolithiasis	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Reproductive system and breast disorders Benign prostatic hyperplasia	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Skin and subcutaneous tissue disorders Rash	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Skin and subcutaneous tissue disorders Rash erythematous	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Skin and subcutaneous tissue disorders Rash maculo-papular	1.6% 2/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Skin and subcutaneous tissue disorders Toxic skin eruption	0.00% 0/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.54% 1/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).

Other adverse events
Measure	Faldaprevir 120mg - 24W n=123 participants at risk Faldaprevir 120 mg QD combined with pegIFN/RBV for 24 weeks, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 12W n=84 participants at risk Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to stop Faldaprevir and continue pegIFN/RBV alone until Week 24; at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg - 24W n=86 participants at risk Faldaprevir 240 mg QD plus pegIFN/RBV for 12 weeks followed by re-randomisation at Week 12 to continue Faldaprevir to Week 24, at Week 24, randomisation of patients who achieved early treatment success (ETS) to an additional 24 weeks of pegIFN/RBV or to stop treatment; patients who did not achieve ETS received pegIFN/RBV until Week 48.	Faldaprevir 240mg -T n=185 participants at risk Faldaprevir 240mg-12w + Faldaprevir 240mg-24w + patients initially randomized or assigned to Faldaprevir 240 mg who discontinued prior to re-randomization at Week 12.
Blood and lymphatic system disorders Anaemia	22.0% 27/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	15.5% 13/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	17.4% 15/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	16.2% 30/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Blood and lymphatic system disorders Neutropenia	22.0% 27/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.1% 6/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	17.4% 15/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	11.9% 22/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Eye disorders Dry eye	2.4% 3/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	6.0% 5/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.2% 6/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Abdominal pain	5.7% 7/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	13.1% 11/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.7% 4/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	9.2% 17/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Abdominal pain upper	5.7% 7/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	8.3% 7/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.5% 3/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	5.4% 10/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Cheilitis	6.5% 8/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.8% 4/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.5% 3/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.8% 7/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Diarrhoea	25.2% 31/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	28.6% 24/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	26.7% 23/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	27.6% 51/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Dry mouth	4.9% 6/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	6.0% 5/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	2.3% 2/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.8% 7/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Dyspepsia	4.9% 6/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.8% 4/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	8.1% 7/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	5.9% 11/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Nausea	27.6% 34/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	45.2% 38/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	41.9% 36/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	43.8% 81/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Gastrointestinal disorders Vomiting	9.8% 12/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	16.7% 14/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	26.7% 23/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	23.2% 43/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
General disorders Asthenia	25.2% 31/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	25.0% 21/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	19.8% 17/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	21.1% 39/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
General disorders Chills	4.1% 5/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	2.4% 2/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	8.1% 7/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	5.9% 11/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
General disorders Fatigue	31.7% 39/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	34.5% 29/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	34.9% 30/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	35.1% 65/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
General disorders Influenza like illness	11.4% 14/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	20.2% 17/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	14.0% 12/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	16.8% 31/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
General disorders Injection site reaction	2.4% 3/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	2.4% 2/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.0% 6/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.3% 8/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
General disorders Irritability	15.4% 19/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	9.5% 8/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	5.8% 5/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.0% 13/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
General disorders Pyrexia	23.6% 29/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	13.1% 11/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	11.6% 10/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	13.0% 24/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Hepatobiliary disorders Jaundice	5.7% 7/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	9.5% 8/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	11.6% 10/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	10.3% 19/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Infections and infestations Oral herpes	6.5% 8/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	0.00% 0/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	2.3% 2/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	1.1% 2/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Investigations Weight decreased	13.0% 16/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	11.9% 10/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	15.1% 13/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	13.5% 25/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Metabolism and nutrition disorders Decreased appetite	23.6% 29/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	16.7% 14/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	20.9% 18/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	19.5% 36/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Musculoskeletal and connective tissue disorders Arthralgia	8.9% 11/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.1% 6/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.0% 6/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.0% 13/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Musculoskeletal and connective tissue disorders Muscle spasms	2.4% 3/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.6% 3/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.0% 6/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.9% 9/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Musculoskeletal and connective tissue disorders Myalgia	13.8% 17/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	10.7% 9/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	17.4% 15/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	14.6% 27/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Nervous system disorders Dizziness	7.3% 9/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	11.9% 10/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.0% 6/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	10.8% 20/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Nervous system disorders Headache	23.6% 29/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	25.0% 21/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	25.6% 22/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	25.4% 47/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Nervous system disorders Lethargy	0.81% 1/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.6% 3/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	5.8% 5/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.3% 8/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Psychiatric disorders Anxiety	7.3% 9/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	6.0% 5/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	2.3% 2/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.3% 8/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Psychiatric disorders Depressed mood	4.9% 6/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.8% 4/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	8.1% 7/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	6.5% 12/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Psychiatric disorders Depression	8.9% 11/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	10.7% 9/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	15.1% 13/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	13.0% 24/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Psychiatric disorders Insomnia	23.6% 29/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	13.1% 11/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	16.3% 14/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	15.1% 28/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Psychiatric disorders Sleep disorder	3.3% 4/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.6% 3/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	5.8% 5/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.3% 8/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Respiratory, thoracic and mediastinal disorders Cough	10.6% 13/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	9.5% 8/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	11.6% 10/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	9.7% 18/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Respiratory, thoracic and mediastinal disorders Dyspnoea	9.8% 12/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	9.5% 8/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.5% 3/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	6.5% 12/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.4% 3/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.1% 6/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	2.3% 2/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.9% 9/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Skin and subcutaneous tissue disorders Alopecia	5.7% 7/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.8% 4/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.0% 6/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	5.4% 10/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Skin and subcutaneous tissue disorders Dry skin	13.8% 17/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	10.7% 9/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	20.9% 18/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	14.6% 27/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Skin and subcutaneous tissue disorders Erythema	6.5% 8/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	6.0% 5/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	5.8% 5/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	5.4% 10/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).
Skin and subcutaneous tissue disorders Night sweats	5.7% 7/123 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	7.1% 6/84 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	3.5% 3/86 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).	4.9% 9/185 • from the start date of trial medication up to 52 weeks ( AEs occurred from the start date of trial medication up to four weeks after all treatment discontinuation).