Trial Outcomes & Findings for Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients (NCT NCT01525628)

NCT ID: NCT01525628

Last Updated: 2016-06-10

Results Overview

Maximum concentration of an analyte in plasma

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

72 participants

Primary outcome timeframe

PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

Results posted on

2016-06-10

Participant Flow

72 patients were treated and analysed.

This was randomised (Groups A and B only), controlled, open-label, parallel-group (Groups A to E), multi-centre trial in treatment-naive patients and patients with prior treatment relapse or partial responders with Genotype 1 (GT1) chronic Hepatitis C infection.

Participant milestones

Participant milestones
Measure	Group A 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Overall Study STARTED	16	19	16	14	7
Overall Study COMPLETED	14	14	11	10	4
Overall Study NOT COMPLETED	2	5	5	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Overall Study Adverse Event	1	1	2	0	1
Overall Study Lack of Efficacy	0	2	2	1	2
Overall Study Protocol Violation	0	0	1	0	0
Overall Study Lost to Follow-up	1	1	0	0	0
Overall Study Withdrawal by Subject	0	1	0	0	0
Overall Study Other reason not defined above	0	0	0	3	0

Baseline Characteristics

Drug Drug Interaction Study Between BI 201335 and BI 207127 in Chronic Hepatitis C Infected Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C n=16 Participants 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D n=14 Participants 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E n=7 Participants 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.	Total n=72 Participants Total of all reporting groups
Age, Continuous	48.2 Years STANDARD_DEVIATION 12.3 • n=5 Participants	53.6 Years STANDARD_DEVIATION 9.3 • n=7 Participants	53.1 Years STANDARD_DEVIATION 9.5 • n=5 Participants	48.4 Years STANDARD_DEVIATION 12.7 • n=4 Participants	52.1 Years STANDARD_DEVIATION 10.4 • n=21 Participants	51.1 Years STANDARD_DEVIATION 10.9 • n=10 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	7 Participants n=4 Participants	1 Participants n=21 Participants	28 Participants n=10 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	7 Participants n=4 Participants	6 Participants n=21 Participants	44 Participants n=10 Participants

PRIMARY outcome

Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9, 17 and 66.

Population: The pharmacokinetic set (PKS): included all patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK. This endpoint was not planned to be analysed for groups C, D and E.

Maximum concentration of an analyte in plasma

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Cmax of Faldaprevir (BI 201335) Day 9 (N=15,0)	3520 ng/mL Geometric Coefficient of Variation 54.8	NA ng/mL Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group B.	—	—	—
Cmax of Faldaprevir (BI 201335) Day 17 (N=14,14)	8780 ng/mL Geometric Coefficient of Variation 47.5	9950 ng/mL Geometric Coefficient of Variation 51.0	—	—	—
Cmax of Faldaprevir (BI 201335) Day 66 (N=13,15)	4410 ng/mL Geometric Coefficient of Variation 48.7	6690 ng/mL Geometric Coefficient of Variation 78.8	—	—	—

PRIMARY outcome

Concentration of an analyte in plasma at 24 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
C24hr of Faldaprevir (BI 201335) Day 9 (N=15,0)	983 ng/mL Geometric Coefficient of Variation 65.5	NA ng/mL Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group B.	—	—	—
C24hr of Faldaprevir (BI 201335) Day 17 (N=14,19)	3670 ng/mL Geometric Coefficient of Variation 90.4	5410 ng/mL Geometric Coefficient of Variation 91.6	—	—	—
C24hr of Faldaprevir (BI 201335) Day 66 (N=13,14)	1140 ng/mL Geometric Coefficient of Variation 107	2580 ng/mL Geometric Coefficient of Variation 135	—	—	—

PRIMARY outcome

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours Day 9 (N=15,0)	45600 ng*h/mL Geometric Coefficient of Variation 54.5	NA ng*h/mL Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group B.	—	—	—
Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours Day 17 (N=14,19)	138000 ng*h/mL Geometric Coefficient of Variation 62.1	173000 ng*h/mL Geometric Coefficient of Variation 60.8	—	—	—
Area Under the Concentration-time Curve (AUC) of Faldaprevir (BI 201335) From 0 to 24 Hours Day 66 (N=13,15)	56200 ng*h/mL Geometric Coefficient of Variation 58.2	97300 ng*h/mL Geometric Coefficient of Variation 114	—	—	—

PRIMARY outcome

Maximum concentration of an analyte in plasma

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Cmax of Deleobuvir (BI 207127) Day 9 (N=0, 17)	NA nmol/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	10900 nmol/L Geometric Coefficient of Variation 85.3	—	—	—
Cmax of Deleobuvir (BI 207127) Day 17 (N=14, 19)	27000 nmol/L Geometric Coefficient of Variation 64.6	31400 nmol/L Geometric Coefficient of Variation 45.8	—	—	—
Cmax of Deleobuvir (BI 207127) Day 66 (N=13, 15)	10100 nmol/L Geometric Coefficient of Variation 78.2	16000 nmol/L Geometric Coefficient of Variation 100	—	—	—

PRIMARY outcome

Concentration of an analyte in plasma at 6 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
C6hr of Deleobuvir (BI 207127) Day 9 (N=0, 17)	NA nmol/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	5800 nmol/L Geometric Coefficient of Variation 129	—	—	—
C6hr of Deleobuvir (BI 207127) Day 17 (N=14, 19)	17900 nmol/L Geometric Coefficient of Variation 84.2	20800 nmol/L Geometric Coefficient of Variation 83.8	—	—	—
C6hr of Deleobuvir (BI 207127) Day 66 (N=13, 14)	5080 nmol/L Geometric Coefficient of Variation 108	10100 nmol/L Geometric Coefficient of Variation 133	—	—	—

PRIMARY outcome

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
AUC 0-6hr of Deleobuvir (BI 207127) Day 9 (N=0, 17)	NA nmol*h/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	41100 nmol*h/L Geometric Coefficient of Variation 93.7	—	—	—
AUC 0-6hr of Deleobuvir (BI 207127) Day 17 (N=14, 19)	119000 nmol*h/L Geometric Coefficient of Variation 73.7	135000 nmol*h/L Geometric Coefficient of Variation 65.0	—	—	—
AUC 0-6hr of Deleobuvir (BI 207127) Day 66 (N=13, 15)	36200 nmol*h/L Geometric Coefficient of Variation 89.0	59200 nmol*h/L Geometric Coefficient of Variation 129	—	—	—

PRIMARY outcome

Maximum concentration of an analyte in plasma

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) Day 9 (N=0, 17)	NA nmol/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	5620 nmol/L Geometric Coefficient of Variation 119	—	—	—
Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) Day 17 (N=14, 19)	12700 nmol/L Geometric Coefficient of Variation 89.4	20200 nmol/L Geometric Coefficient of Variation 111	—	—	—
Cmax of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) Day 66 (N=13, 15)	3790 nmol/L Geometric Coefficient of Variation 66.9	6550 nmol/L Geometric Coefficient of Variation 98.3	—	—	—

PRIMARY outcome

Concentration of an analyte in plasma at 6 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) Day 9 (N=0, 17)	NA nmol/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	4330 nmol/L Geometric Coefficient of Variation 154	—	—	—
C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) Day 17 (N=14, 19)	11200 nmol/L Geometric Coefficient of Variation 83.7	17500 nmol/L Geometric Coefficient of Variation 119	—	—	—
C6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) Day 66 (N=13, 14)	2740 nmol/L Geometric Coefficient of Variation 85.9	5780 nmol/L Geometric Coefficient of Variation 132	—	—	—

PRIMARY outcome

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) Day 9 (N=0, 17)	NA nmol*h/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	24300 nmol*h/L Geometric Coefficient of Variation 131	—	—	—
AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) Day 17 (N=14, 19)	61800 nmol*h/L Geometric Coefficient of Variation 97.9	98800 nmol*h/L Geometric Coefficient of Variation 124	—	—	—
AUC 0-6hr of Deleobuvir Metabolite Acyl-glucuronide (BI 208333) Day 66 (N=13, 15)	15000 nmol*h/L Geometric Coefficient of Variation 81.2	27600 nmol*h/L Geometric Coefficient of Variation 128	—	—	—

PRIMARY outcome

Maximum concentration of an analyte in plasma

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Cmax of Deleobuvir Reduction Metabolite CD 6168 Day 66 (N=13, 15)	4510 nmol/L Geometric Coefficient of Variation 117	8880 nmol/L Geometric Coefficient of Variation 111	—	—	—
Cmax of Deleobuvir Reduction Metabolite CD 6168 Day 9 (N=0, 17)	NA nmol/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	3040 nmol/L Geometric Coefficient of Variation 115	—	—	—
Cmax of Deleobuvir Reduction Metabolite CD 6168 Day 17 (N=14, 19)	8520 nmol/L Geometric Coefficient of Variation 119	12400 nmol/L Geometric Coefficient of Variation 70.9	—	—	—

PRIMARY outcome

Concentration of an analyte in plasma at 6 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
C6hr of Deleobuvir Reduction Metabolite CD 6168 Day 9 (N=0, 17)	NA nmol/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	2250 nmol/L Geometric Coefficient of Variation 137	—	—	—
C6hr of Deleobuvir Reduction Metabolite CD 6168 Day 17 (N=14, 19)	6980 nmol/L Geometric Coefficient of Variation 128	10200 nmol/L Geometric Coefficient of Variation 81.0	—	—	—
C6hr of Deleobuvir Reduction Metabolite CD 6168 Day 66 (N=13, 14)	3360 nmol/L Geometric Coefficient of Variation 139	7460 nmol/L Geometric Coefficient of Variation 123	—	—	—

PRIMARY outcome

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 Day 9 (N=0, 17)	NA nmol*h/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	13300 nmol*h/L Geometric Coefficient of Variation 123	—	—	—
AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 Day 17 (N=14, 19)	41700 nmol*h/L Geometric Coefficient of Variation 130	62200 nmol*h/L Geometric Coefficient of Variation 82.7	—	—	—
AUC 0-6hr of Deleobuvir Reduction Metabolite CD 6168 Day 66 (N=13, 15)	19300 nmol*h/L Geometric Coefficient of Variation 134	39100 nmol*h/L Geometric Coefficient of Variation 133	—	—	—

PRIMARY outcome

Maximum concentration of an analyte in plasma

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) Day 17 (N=14, 19)	596 nmol/L Geometric Coefficient of Variation 143	1130 nmol/L Geometric Coefficient of Variation 115	—	—	—
Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) Day 9 (N=0, 17)	NA nmol/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	203 nmol/L Geometric Coefficient of Variation 135	—	—	—
Cmax of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) Day 66 (N=13, 15)	386 nmol/L Geometric Coefficient of Variation 111	806 nmol/L Geometric Coefficient of Variation 125	—	—	—

PRIMARY outcome

Concentration of an analyte in plasma at 6 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) Day 9 (N=0, 17)	NA nmol/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	159 nmol/L Geometric Coefficient of Variation 165	—	—	—
C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) Day 17 (N=14, 19)	508 nmol/L Geometric Coefficient of Variation 138	962 nmol/L Geometric Coefficient of Variation 117	—	—	—
C6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) Day 66 (N=13, 14)	295 nmol/L Geometric Coefficient of Variation 128	712 nmol/L Geometric Coefficient of Variation 143	—	—	—

PRIMARY outcome

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 6 hours

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) Day 9 (N=0, 17)	NA nmol*h/L Geometric Coefficient of Variation NA Not calculated as this timepoint was not planned to be analysed for group A.	893 nmol*h/L Geometric Coefficient of Variation 142	—	—	—
AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) Day 17 (N=14, 19)	2980 nmol*h/L Geometric Coefficient of Variation 151	5700 nmol*h/L Geometric Coefficient of Variation 123	—	—	—
AUC 0-6hr of Deleobuvir Metabolite CD 6168 ag (Acylglucuronide) Day 66 (N=13, 15)	1620 nmol*h/L Geometric Coefficient of Variation 133	3510 nmol*h/L Geometric Coefficient of Variation 143	—	—	—

PRIMARY outcome

Timeframe: 5 min before and 1 hour (h), 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11:55h, 15h, 23:55h, 26h, 28h, 29:55h, 32h after first drug administration on day 1 also 5 min before, 1h, 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after drug on days 9, 17 and 66.

Population: PKS. This endpoint was not planned to be analysed for groups C, D and E

Maximum concentration of an analyte in plasma

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Cmax of Caffeine Day 1 (N=16, 19)	5170 ng/mL Geometric Coefficient of Variation 46.2	5340 ng/mL Geometric Coefficient of Variation 38.2	—	—	—
Cmax of Caffeine Day 9 (N=15, 17)	4890 ng/mL Geometric Coefficient of Variation 57.7	7220 ng/mL Geometric Coefficient of Variation 37.1	—	—	—
Cmax of Caffeine Day 17 (N=14, 19)	4830 ng/mL Geometric Coefficient of Variation 47.5	6530 ng/mL Geometric Coefficient of Variation 52.3	—	—	—
Cmax of Caffeine Day 66 (N=13, 15)	5590 ng/mL Geometric Coefficient of Variation 49.6	6450 ng/mL Geometric Coefficient of Variation 32.4	—	—	—

PRIMARY outcome

Population: PKS. This endpoint was not planned to be analysed for groups C, D and E

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
AUC 0-infinity of Caffeine Day 1 (N=16, 19)	54900 ng*h/mL Geometric Coefficient of Variation 130	77500 ng*h/mL Geometric Coefficient of Variation 119	—	—	—
AUC 0-infinity of Caffeine Day 9 (N=15, 15)	42100 ng*h/mL Geometric Coefficient of Variation 96	142000 ng*h/mL Geometric Coefficient of Variation 109	—	—	—
AUC 0-infinity of Caffeine Day 17 (N=14, 19)	71900 ng*h/mL Geometric Coefficient of Variation 169	170000 ng*h/mL Geometric Coefficient of Variation 203	—	—	—
AUC 0-infinity of Caffeine Day 66 (N=13, 15)	120000 ng*h/mL Geometric Coefficient of Variation 220	159000 ng*h/mL Geometric Coefficient of Variation 138	—	—	—

PRIMARY outcome

Population: PKS. This endpoint was not planned to be analysed for groups C, D and E

Maximum concentration of an analyte in plasma

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Cmax of Tolbutamide Day 1 (N=16, 19)	152000 nmol/L Geometric Coefficient of Variation 30.8	170000 nmol/L Geometric Coefficient of Variation 18.6	—	—	—
Cmax of Tolbutamide Day 9 (N=15, 17)	146000 nmol/L Geometric Coefficient of Variation 28.1	158000 nmol/L Geometric Coefficient of Variation 22.8	—	—	—
Cmax of Tolbutamide Day 17 (N=14, 19)	130000 nmol/L Geometric Coefficient of Variation 24.7	126000 nmol/L Geometric Coefficient of Variation 32.0	—	—	—
Cmax of Tolbutamide Day 66 (N=13, 15)	110000 nmol/L Geometric Coefficient of Variation 32.3	127000 nmol/L Geometric Coefficient of Variation 25.0	—	—	—

PRIMARY outcome

Population: PKS. This endpoint was not planned to be analysed for groups C, D and E

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
AUC 0-infinity of Tolbutamide Day 1 (N=16, 19)	1940000 nmol*h/L Geometric Coefficient of Variation 42.5	2220000 nmol*h/L Geometric Coefficient of Variation 29.4	—	—	—
AUC 0-infinity of Tolbutamide Day 9 (N=13, 17)	1800000 nmol*h/L Geometric Coefficient of Variation 41.3	1940000 nmol*h/L Geometric Coefficient of Variation 36.5	—	—	—
AUC 0-infinity of Tolbutamide Day 17 (N=14, 18)	1520000 nmol*h/L Geometric Coefficient of Variation 36.4	1410000 nmol*h/L Geometric Coefficient of Variation 27.9	—	—	—
AUC 0-infinity of Tolbutamide Day 66 (N=12, 15)	1330000 nmol*h/L Geometric Coefficient of Variation 40.1	1390000 nmol*h/L Geometric Coefficient of Variation 33.2	—	—	—

PRIMARY outcome

Population: PKS. This endpoint was not planned to be analysed for groups C, D and E

Maximum concentration of an analyte in plasma

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Cmax of Midazolam Day 1 (N=16, 19)	21.1 nmol/L Geometric Coefficient of Variation 38.3	23.8 nmol/L Geometric Coefficient of Variation 41.2	—	—	—
Cmax of Midazolam Day 9 (N=15, 17)	29.9 nmol/L Geometric Coefficient of Variation 34.7	29.8 nmol/L Geometric Coefficient of Variation 44.3	—	—	—
Cmax of Midazolam Day 17 (N=14, 19)	31.9 nmol/L Geometric Coefficient of Variation 36.6	28.8 nmol/L Geometric Coefficient of Variation 46.9	—	—	—
Cmax of Midazolam Day 66 (N=13, 15)	21.3 nmol/L Geometric Coefficient of Variation 34.0	23.2 nmol/L Geometric Coefficient of Variation 40.4	—	—	—

PRIMARY outcome

Population: PKS. This endpoint was not planned to be analysed for groups C, D and E

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
AUC 0-infinity of Midazolam Day 1 (N=16, 19)	79.7 nmol*h/L Geometric Coefficient of Variation 59.1	107 nmol*h/L Geometric Coefficient of Variation 40.7	—	—	—
AUC 0-infinity of Midazolam Day 9 (N=15, 17)	117 nmol*h/L Geometric Coefficient of Variation 58.2	130 nmol*h/L Geometric Coefficient of Variation 66.9	—	—	—
AUC 0-infinity of Midazolam Day 17 (N=14, 19)	127 nmol*h/L Geometric Coefficient of Variation 50.2	140 nmol*h/L Geometric Coefficient of Variation 51.8	—	—	—
AUC 0-infinity of Midazolam Day 66 (N=13, 15)	75.5 nmol*h/L Geometric Coefficient of Variation 46.7	95.6 nmol*h/L Geometric Coefficient of Variation 41.6	—	—	—

PRIMARY outcome

Population: PKS. This endpoint was not planned to be analysed for groups C, D and E

Maximum concentration of an analyte in plasma

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) Day 1 (N=16, 19)	5.57 nmol/L Geometric Coefficient of Variation 36.4	6.68 nmol/L Geometric Coefficient of Variation 67.1	—	—	—
Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) Day 9 (N=15, 17)	6.50 nmol/L Geometric Coefficient of Variation 46.3	6.52 nmol/L Geometric Coefficient of Variation 46.9	—	—	—
Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) Day 17 (N=14, 19)	6.46 nmol/L Geometric Coefficient of Variation 42.7	5.02 nmol/L Geometric Coefficient of Variation 50.5	—	—	—
Cmax of 1-OH-Midazolam (1-hydroxy-midazolam) Day 66 (N=13, 15)	5.05 nmol/L Geometric Coefficient of Variation 45.6	4.67 nmol/L Geometric Coefficient of Variation 45.2	—	—	—

PRIMARY outcome

Population: PKS. This endpoint was not planned to be analysed for groups C, D and E

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity.

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) Day 1 (N=16, 19)	23.6 nmol*h/L Geometric Coefficient of Variation 59.8	26.0 nmol*h/L Geometric Coefficient of Variation 65.2	—	—	—
AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) Day 9 (N=15, 17)	24.2 nmol*h/L Geometric Coefficient of Variation 35.9	28.5 nmol*h/L Geometric Coefficient of Variation 63.9	—	—	—
AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) Day 17 (N=14, 19)	23.5 nmol*h/L Geometric Coefficient of Variation 37.4	22.8 nmol*h/L Geometric Coefficient of Variation 49.8	—	—	—
AUC 0-infinity of 1-OH-Midazolam (1-hydroxy-midazolam) Day 66 (N=13, 13)	18.3 nmol*h/L Geometric Coefficient of Variation 26.7	20.8 nmol*h/L Geometric Coefficient of Variation 46.1	—	—	—

PRIMARY outcome

Timeframe: PK plasma samples were taken at: 5 minutes before drug administration and 1 hour (h), 2h, 3h, 4h, 5h, 5:55h, 8h, 10h, 11:55h, 15h, 23:55h after first drug administration on days 9 and 17

Timeframe: 12 weeks post treatment

Population: Treated set (TRT): This subject set includes all patients who were dispensed trial medication and were documented to have taken at least one dose of trial drug.

Sustained virologic response (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level \<25 IU/mL(international units per millilitre) undetectable at 12 weeks after the end of treatment. SVR12 was analyzed in a descriptive manner using frequency of participants who achieved SVR12.

Outcome measures

Outcome measures
Measure	Group A n=16 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 Participants 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C n=16 Participants 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D n=14 Participants 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E n=7 Participants 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Number of Participants With Sustained Virological Response (SVR12)	13 Participants	13 Participants	11 Participants	10 Participants	3 Participants

Adverse Events

Group A

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Group B

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Group C

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Group D

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Group E

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group A n=16 participants at risk 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 participants at risk 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C n=16 participants at risk 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D n=14 participants at risk 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E n=7 participants at risk 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Gastrointestinal disorders Colitis ulcerative	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Nausea	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Complex partial seizures	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Acute psychosis	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Bipolar disorder	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Reactive psychosis	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.

Other adverse events

Other adverse events
Measure	Group A n=16 participants at risk 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a(PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group A the effect of DBV on FDV, the effect of FDV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group B n=19 participants at risk 600mg deleobuvir(DBV) tablet taken orally 3 times a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks along with pegylated interferon α-2a (PegIFN) injection and probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66). In group B the effect of FDV on DBV, the effect of DBV, dual oral direct acting antiviral (DAAs) and their metabolites on caffeine, tolbutamide and midazolam were determined.	Group C n=16 participants at risk 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with tenofovir tablet 300mg daily on days 1-17.	Group D n=14 participants at risk 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily with probe drugs(200 mg caffeine tablet, 500 mg tolbutamide tablet, and 2 mg midazolam syrup administered orally on days 1, 9, 17, and 66).	Group E n=7 participants at risk 600mg deleobuvir(DBV) tablet taken twice a day plus 120mg faldaprevir(FDV) capsule taken orally once daily plus ribavirin(RBV) tablet taken orally twice daily for 24 weeks with raltegravir tablet 400mg twice daily on days 1-17.
Musculoskeletal and connective tissue disorders Flank pain	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Blood and lymphatic system disorders Anaemia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Blood and lymphatic system disorders Leukopenia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Blood and lymphatic system disorders Neutropenia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 2/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Cardiac disorders Angina pectoris	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Cardiac disorders Cardiovascular disorder	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Cardiac disorders Palpitations	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Ear and labyrinth disorders Ear discomfort	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Ear and labyrinth disorders Ear pain	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Ear and labyrinth disorders Tinnitus	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Ear and labyrinth disorders Vertigo	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Endocrine disorders Hypothyroidism	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Blepharospasm	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Conjunctival haemorrhage	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Eye irritation	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Eye pain	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Eyelids pruritus	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Lacrimation increased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Ocular hyperaemia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Ocular icterus	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	35.7% 5/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Periorbital oedema	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Photophobia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Retinal exudates	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Vision blurred	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Eye disorders Visual acuity reduced	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Abdominal distension	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.1% 4/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Abdominal pain	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	25.0% 4/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 4/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	25.0% 4/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.4% 3/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Abdominal rigidity	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Abdominal tenderness	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Anal pruritus	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Anorectal discomfort	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Chapped lips	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Cheilitis	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Constipation	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	25.0% 4/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.4% 3/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Diarrhoea	31.2% 5/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	52.6% 10/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	25.0% 4/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.4% 3/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	42.9% 3/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Dry mouth	25.0% 4/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Dyspepsia	37.5% 6/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 4/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Faeces discoloured	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Flatulence	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Gastrointestinal motility disorder	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Gastrooesophageal reflux disease	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Gingival pain	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Glossodynia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Haematochezia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Haemorrhoids	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Lip dry	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Lip erosion	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Lip haemorrhage	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Lip oedema	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Lip pain	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Mucous stools	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Nausea	75.0% 12/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	84.2% 16/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	75.0% 12/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	71.4% 10/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Oral discomfort	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Oral disorder	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Oral pain	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Paraesthesia oral	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Salivary hypersecretion	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Stomatitis	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Tongue discolouration	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Toothache	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Gastrointestinal disorders Vomiting	31.2% 5/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	57.9% 11/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	43.8% 7/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	35.7% 5/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Asthenia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	31.6% 6/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Chest discomfort	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Chills	37.5% 6/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	36.8% 7/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Energy increased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Fatigue	56.2% 9/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	57.9% 11/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	50.0% 8/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	57.1% 8/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Feeling hot	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Feeling of body temperature change	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Feeling of relaxation	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Influenza like illness	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Injection site bruising	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Injection site haematoma	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Injection site pain	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Injection site reaction	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Local swelling	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Malaise	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Nodule	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Oedema	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Oedema peripheral	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Pain	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Peripheral swelling	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Pyrexia	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Temperature intolerance	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Tenderness	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Unevaluable event	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
General disorders Vessel puncture site pain	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Hepatobiliary disorders Cholelithiasis	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Hepatobiliary disorders Hepatomegaly	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	25.0% 4/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	50.0% 7/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	57.1% 4/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Hepatobiliary disorders Jaundice	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 4/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Body tinea	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Bronchitis	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Cellulitis	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Fungal infection	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Gastritis viral	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Genital herpes	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Influenza	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Localised infection	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Lower respiratory tract infection	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Nasopharyngitis	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.4% 3/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Oral herpes	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Otitis externa	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Post procedural infection	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Staphylococcal infection	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Tinea pedis	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Tooth infection	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Infections and infestations Urinary tract infection	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Injury, poisoning and procedural complications Animal bite	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Injury, poisoning and procedural complications Foot fracture	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Injury, poisoning and procedural complications Laceration	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Injury, poisoning and procedural complications Ligament sprain	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Injury, poisoning and procedural complications Scratch	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Injury, poisoning and procedural complications Skin wound	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Injury, poisoning and procedural complications Sunburn	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.4% 3/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Injury, poisoning and procedural complications Wound	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Investigations Blood bilirubin increased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Investigations Blood creatinine increased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Investigations Blood pressure increased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Investigations Blood uric acid increased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Investigations Glomerular filtration rate decreased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Investigations Haemoglobin decreased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Investigations Weight decreased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 2/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Metabolism and nutrition disorders Decreased appetite	37.5% 6/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	42.1% 8/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	35.7% 5/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Metabolism and nutrition disorders Dehydration	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Metabolism and nutrition disorders Food craving	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Metabolism and nutrition disorders Gout	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Metabolism and nutrition disorders Increased appetite	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	37.5% 6/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.1% 4/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Fibromyalgia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Muscle spasms	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Myalgia	31.2% 5/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.1% 4/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Amnesia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Balance disorder	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Burning sensation	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Cognitive disorder	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Disturbance in attention	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Dizziness	37.5% 6/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	26.3% 5/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Dysaesthesia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Dysgeusia	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Headache	56.2% 9/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	47.4% 9/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	31.2% 5/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	35.7% 5/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Hyperaesthesia	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Hypertonia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Hypoaesthesia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Hypogeusia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Lethargy	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Memory impairment	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Mental impairment	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Migraine	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Paraesthesia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Parosmia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Presyncope	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Psychomotor hyperactivity	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Restless legs syndrome	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Sciatica	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Sleep phase rhythm disturbance	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Somnolence	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Syncope	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Nervous system disorders Tremor	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Affect lability	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Agitation	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Anxiety	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Depressed mood	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Depression	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Disorientation	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Flat affect	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Frustration	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Hallucination, visual	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Impatience	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Insomnia	50.0% 8/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	26.3% 5/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Irritability	31.2% 5/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.1% 4/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Libido increased	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Sleep disorder	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.4% 3/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Psychiatric disorders Stress	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Renal and urinary disorders Chromaturia	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Renal and urinary disorders Dysuria	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Renal and urinary disorders Nocturia	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Renal and urinary disorders Pollakiuria	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Renal and urinary disorders Renal disorder	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Renal and urinary disorders Renal failure	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Reproductive system and breast disorders Erectile dysfunction	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Reproductive system and breast disorders Vaginal discharge	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 4/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Respiratory, thoracic and mediastinal disorders Nasal dryness	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	7.1% 1/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Acne	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Acute febrile neutrophilic dermatosis	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Alopecia	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	15.8% 3/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Angioedema	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Blister	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Dermatitis contact	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Dry skin	31.2% 5/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.1% 4/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 2/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Erythema	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.4% 3/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.1% 4/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Macule	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Nail atrophy	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Nail discolouration	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Pain of skin	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	31.6% 6/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	18.8% 3/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Papule	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Petechiae	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Photosensitivity reaction	56.2% 9/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	42.1% 8/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Pruritus	43.8% 7/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	52.6% 10/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	37.5% 6/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	64.3% 9/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	28.6% 2/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Pruritus generalised	12.5% 2/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Psoriasis	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Rash	37.5% 6/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	36.8% 7/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	31.2% 5/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	57.1% 4/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Rash maculo-papular	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Skin burning sensation	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Skin irritation	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Skin lesion	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Skin mass	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Skin reaction	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	21.4% 3/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Skin warm	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Vitiligo	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Skin and subcutaneous tissue disorders Xeroderma	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Surgical and medical procedures Tooth extraction	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	10.5% 2/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Vascular disorders Haematoma	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 1/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Vascular disorders Hot flush	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	6.2% 1/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Vascular disorders Hypertension	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	14.3% 2/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.
Vascular disorders Pallor	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	5.3% 1/19 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/16 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/14 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.	0.00% 0/7 • From first drug administration until last drug administration plus 28 days, up to 28 weeks.

Additional Information

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