Trial Outcomes & Findings for Multiple Oral Doses of BI 207127 NA in Treatment naïve and Treatment-experienced Hepatitis C Virus (HCV)-Infected Patients (NCT NCT02176525)

Last Updated: 2016-06-06

Results Overview

Virologic response was defined as a ≥ 1 log10 reduction in serum Hepatitis C virus (HCV) Ribonucleic acid (RNA) level from baseline at any time from the start of administration of treatment up to day 5. In this Outcome Measure the percentage of participants with virologic response is presented.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

75 participants

Primary outcome timeframe

Baseline (Visit 2_2 at planned time 5 minutes prior to first administration of trial drug), up to day 5

Results posted on

2016-06-06

Participant Flow

acronyms used in pre-assignment details: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP)

Each patient participating in the trial (or the patient's legally accepted representative) provided written informed consent according to ICH GCP and the regulatory and legal requirements of the participating country. All subjects were informed that they were free to withdraw their consent at any time during the study without penalty or prejudice.

Participant milestones

Participant milestones
Measure	Placebo Fibrosis Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis Deleobuvir (DBV) 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Overall Study STARTED	15	9	9	9	8	6	9	10
Overall Study COMPLETED	14	9	9	8	7	5	8	10
Overall Study NOT COMPLETED	1	0	0	1	1	1	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Fibrosis Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis Deleobuvir (DBV) 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Overall Study Adverse Event	0	0	0	1	1	0	1	0
Overall Study not treated	1	0	0	0	0	1	0	0

Baseline Characteristics

Multiple Oral Doses of BI 207127 NA in Treatment naïve and Treatment-experienced Hepatitis C Virus (HCV)-Infected Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=9 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=5 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis n=10 Participants DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	Total n=73 Participants Total of all reporting groups
Age, Continuous	47.2 years STANDARD_DEVIATION 9.1 • n=5 Participants	50.3 years STANDARD_DEVIATION 11.9 • n=7 Participants	51.7 years STANDARD_DEVIATION 8.5 • n=5 Participants	52.3 years STANDARD_DEVIATION 8.7 • n=4 Participants	55.4 years STANDARD_DEVIATION 7.0 • n=21 Participants	56.2 years STANDARD_DEVIATION 8.1 • n=10 Participants	47.3 years STANDARD_DEVIATION 12.7 • n=115 Participants	46.8 years STANDARD_DEVIATION 8.6 • n=24 Participants	50.24 years STANDARD_DEVIATION 9.56 • n=42 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	1 Participants n=10 Participants	2 Participants n=115 Participants	0 Participants n=24 Participants	15 Participants n=42 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants	6 Participants n=21 Participants	4 Participants n=10 Participants	7 Participants n=115 Participants	10 Participants n=24 Participants	58 Participants n=42 Participants

PRIMARY outcome

Timeframe: Baseline (Visit 2_2 at planned time 5 minutes prior to first administration of trial drug), up to day 5

Population: The full analysis set (FAS) included all randomised patients who were dispensed study medication and were documented to have taken at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=9 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=5 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis n=10 Participants DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Virologic Response (VR)	14.3 percentage of participants Interval 4.0 to 40.0	22.2 percentage of participants Interval 7.0 to 56.0	55.6 percentage of participants Interval 26.0 to 81.0	88.9 percentage of participants Interval 55.0 to 97.0	87.5 percentage of participants Interval 52.0 to 97.0	100 percentage of participants Interval 61.0 to 100.0	88.9 percentage of participants Interval 55.0 to 97.0	100 percentage of participants Interval 76.0 to 100.0

SECONDARY outcome

Timeframe: Baseline, up to day 7

Population: The full analysis set (FAS) included all randomised patients who were dispensed study medication and were documented to have taken at least one dose of study medication.

Change of VL from baseline to day 7 is presented (VL at timepoint minus VL at baseline). Acronym used within the categories: planned time (PTM). The number of participants analysed displays the number of participants included in the analysis set whereas the number of participants for each timepoint display the number of participants with available data at that timepoint.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=9 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=5 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis n=10 Participants DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Time Dependent Change From Baseline in Viral Load (VL) PTM 2:00 hours; N (per arm): 14/8/9/9/8/5/8/10	-0.01 log10 (U/L) Standard Deviation 0.15	-0.03 log10 (U/L) Standard Deviation 0.15	-0.06 log10 (U/L) Standard Deviation 0.26	-0.13 log10 (U/L) Standard Deviation 0.11	0.09 log10 (U/L) Standard Deviation 0.10	-0.01 log10 (U/L) Standard Deviation 0.16	0.05 log10 (U/L) Standard Deviation 0.25	0.03 log10 (U/L) Standard Deviation 0.11
Time Dependent Change From Baseline in Viral Load (VL) PTM 4:00 hours; N (per arm): 14/8/9/9/8/5/9/10	-0.11 log10 (U/L) Standard Deviation 0.09	-0.02 log10 (U/L) Standard Deviation 0.21	-0.16 log10 (U/L) Standard Deviation 0.18	-0.25 log10 (U/L) Standard Deviation 0.17	-0.07 log10 (U/L) Standard Deviation 0.22	-0.03 log10 (U/L) Standard Deviation 0.34	-0.26 log10 (U/L) Standard Deviation 0.17	-0.15 log10 (U/L) Standard Deviation 0.20
Time Dependent Change From Baseline in Viral Load (VL) PTM 7:55 hours; N (per arm): 14/8/9/9/8/5/9/9	-0.16 log10 (U/L) Standard Deviation 0.37	-0.33 log10 (U/L) Standard Deviation 0.37	-0.53 log10 (U/L) Standard Deviation 0.60	-0.96 log10 (U/L) Standard Deviation 0.51	-0.90 log10 (U/L) Standard Deviation 0.53	-1.05 log10 (U/L) Standard Deviation 0.30	-1.41 log10 (U/L) Standard Deviation 0.53	-1.11 log10 (U/L) Standard Deviation 0.51
Time Dependent Change From Baseline in Viral Load (VL) PTM 10:00 hours; N (per arm): 14/8/9/9/8/5/9/10	-0.06 log10 (U/L) Standard Deviation 0.19	-0.55 log10 (U/L) Standard Deviation 0.49	-0.80 log10 (U/L) Standard Deviation 0.59	-1.21 log10 (U/L) Standard Deviation 0.60	-1.26 log10 (U/L) Standard Deviation 0.53	-1.57 log10 (U/L) Standard Deviation 0.56	-1.82 log10 (U/L) Standard Deviation 0.59	-1.59 log10 (U/L) Standard Deviation 0.54
Time Dependent Change From Baseline in Viral Load (VL) PTM 15:55 hours; N (per arm): 14/8/9/9/8/5/9/10	-0.00 log10 (U/L) Standard Deviation 0.19	-0.53 log10 (U/L) Standard Deviation 0.57	-0.96 log10 (U/L) Standard Deviation 0.78	-1.66 log10 (U/L) Standard Deviation 0.96	-1.89 log10 (U/L) Standard Deviation 0.69	-2.30 log10 (U/L) Standard Deviation 0.55	-2.40 log10 (U/L) Standard Deviation 0.76	-2.31 log10 (U/L) Standard Deviation 0.57
Time Dependent Change From Baseline in Viral Load (VL) PTM 18:00 hours; N (per arm): 14/8/9/9/8/5/9/10	-0.01 log10 (U/L) Standard Deviation 0.18	-0.43 log10 (U/L) Standard Deviation 0.55	-0.94 log10 (U/L) Standard Deviation 0.69	-1.64 log10 (U/L) Standard Deviation 0.96	-1.96 log10 (U/L) Standard Deviation 0.69	-2.49 log10 (U/L) Standard Deviation 0.57	-2.51 log10 (U/L) Standard Deviation 0.86	-2.40 log10 (U/L) Standard Deviation 0.63
Time Dependent Change From Baseline in Viral Load (VL) PTM 23:55 hours; N (per arm): 14/8/9/9/7/5/9/10	0.01 log10 (U/L) Standard Deviation 0.17	-0.53 log10 (U/L) Standard Deviation 0.64	-0.93 log10 (U/L) Standard Deviation 0.82	-1.67 log10 (U/L) Standard Deviation 1.02	-2.03 log10 (U/L) Standard Deviation 0.79	-2.75 log10 (U/L) Standard Deviation 0.77	-2.46 log10 (U/L) Standard Deviation 1.04	-2.45 log10 (U/L) Standard Deviation 0.83
Time Dependent Change From Baseline in Viral Load (VL) PTM 47:55 hours; N (per arm): 13/7/9/9/7/5/9/10	-0.01 log10 (U/L) Standard Deviation 0.18	-0.46 log10 (U/L) Standard Deviation 0.65	-1.14 log10 (U/L) Standard Deviation 1.26	-1.79 log10 (U/L) Standard Deviation 1.25	-2.43 log10 (U/L) Standard Deviation 0.88	-3.14 log10 (U/L) Standard Deviation 0.67	-3.00 log10 (U/L) Standard Deviation 1.14	-3.01 log10 (U/L) Standard Deviation 0.59
Time Dependent Change From Baseline in Viral Load (VL) PTM 71:55 hours; N (per arm): 14/8/9/8/7/5/9/10	-0.06 log10 (U/L) Standard Deviation 0.16	-0.50 log10 (U/L) Standard Deviation 0.65	-1.16 log10 (U/L) Standard Deviation 0.92	-1.84 log10 (U/L) Standard Deviation 1.43	-2.50 log10 (U/L) Standard Deviation 0.93	-3.17 log10 (U/L) Standard Deviation 0.59	-3.02 log10 (U/L) Standard Deviation 1.30	-2.97 log10 (U/L) Standard Deviation 0.82
Time Dependent Change From Baseline in Viral Load (VL) PTM 95:55 hours; N (per arm): 14/8/9/8/7/5/9/10	-0.04 log10 (U/L) Standard Deviation 0.27	-0.61 log10 (U/L) Standard Deviation 0.65	-1.07 log10 (U/L) Standard Deviation 0.94	-1.87 log10 (U/L) Standard Deviation 1.33	-2.64 log10 (U/L) Standard Deviation 1.19	-3.19 log10 (U/L) Standard Deviation 0.56	-3.11 log10 (U/L) Standard Deviation 1.23	-2.94 log10 (U/L) Standard Deviation 0.83
Time Dependent Change From Baseline in Viral Load (VL) PTM 98:00 hours; N (per arm): 14/8/9/8/8/5/9/10	-0.08 log10 (U/L) Standard Deviation 0.26	-0.66 log10 (U/L) Standard Deviation 0.65	-1.08 log10 (U/L) Standard Deviation 0.89	-1.93 log10 (U/L) Standard Deviation 1.29	-2.64 log10 (U/L) Standard Deviation 1.13	-3.13 log10 (U/L) Standard Deviation 0.67	-3.17 log10 (U/L) Standard Deviation 1.29	-3.01 log10 (U/L) Standard Deviation 0.77
Time Dependent Change From Baseline in Viral Load (VL) PTM 100:00 hours; N (per arm): 14/8/9/8/7/5/8/10	-0.17 log10 (U/L) Standard Deviation 0.24	-0.60 log10 (U/L) Standard Deviation 0.58	-1.05 log10 (U/L) Standard Deviation 0.80	-1.94 log10 (U/L) Standard Deviation 1.24	-2.70 log10 (U/L) Standard Deviation 1.23	-3.16 log10 (U/L) Standard Deviation 0.83	-3.06 log10 (U/L) Standard Deviation 1.40	-3.02 log10 (U/L) Standard Deviation 0.78
Time Dependent Change From Baseline in Viral Load (VL) PTM 104:00 hours; N (per arm): 13/8/9/8/0/0/8/10	-0.07 log10 (U/L) Standard Deviation 0.19	-0.77 log10 (U/L) Standard Deviation 0.63	-1.08 log10 (U/L) Standard Deviation 0.92	-1.96 log10 (U/L) Standard Deviation 1.25	NA log10 (U/L) Standard Deviation NA N=0	NA log10 (U/L) Standard Deviation NA N=0	-3.27 log10 (U/L) Standard Deviation 1.30	-3.11 log10 (U/L) Standard Deviation 0.82
Time Dependent Change From Baseline in Viral Load (VL) PTM 108:00 hours; N (per arm): 14/8/9/8/8/5/8/10	-0.06 log10 (U/L) Standard Deviation 0.20	-0.56 log10 (U/L) Standard Deviation 0.53	-0.90 log10 (U/L) Standard Deviation 1.01	-1.80 log10 (U/L) Standard Deviation 1.25	-2.61 log10 (U/L) Standard Deviation 1.17	-3.19 log10 (U/L) Standard Deviation 0.58	-3.11 log10 (U/L) Standard Deviation 1.20	-3.03 log10 (U/L) Standard Deviation 0.83
Time Dependent Change From Baseline in Viral Load (VL) PTM 112:00 hours; N (per arm): 14/8/9/8/6/5/8/10	-0.03 log10 (U/L) Standard Deviation 0.18	-0.56 log10 (U/L) Standard Deviation 0.50	-0.87 log10 (U/L) Standard Deviation 0.85	-1.64 log10 (U/L) Standard Deviation 1.35	-2.95 log10 (U/L) Standard Deviation 1.25	-3.12 log10 (U/L) Standard Deviation 0.71	-2.98 log10 (U/L) Standard Deviation 1.30	-2.91 log10 (U/L) Standard Deviation 0.90
Time Dependent Change From Baseline in Viral Load (VL) PTM 120:00 hours; N (per arm): 14/8/9/8/6/5/8/10	-0.14 log10 (U/L) Standard Deviation 0.50	-0.37 log10 (U/L) Standard Deviation 0.41	-0.70 log10 (U/L) Standard Deviation 0.68	-1.47 log10 (U/L) Standard Deviation 1.29	-2.20 log10 (U/L) Standard Deviation 1.46	-2.97 log10 (U/L) Standard Deviation 1.13	-2.82 log10 (U/L) Standard Deviation 1.40	-2.64 log10 (U/L) Standard Deviation 1.07
Time Dependent Change From Baseline in Viral Load (VL) PTM 144:00 hours; N (per arm): 14/8/9/8/0/1/6/10	0.02 log10 (U/L) Standard Deviation 0.76	-0.19 log10 (U/L) Standard Deviation 0.38	-0.40 log10 (U/L) Standard Deviation 0.93	-0.76 log10 (U/L) Standard Deviation 1.07	NA log10 (U/L) Standard Deviation NA N=0	-2.93 log10 (U/L) Standard Deviation NA N=1	-1.88 log10 (U/L) Standard Deviation 1.64	-1.61 log10 (U/L) Standard Deviation 0.87

SECONDARY outcome

Timeframe: 5 minutes (min) prior to the first dose of study medication and 30 minutes and 1:00, 2:00, 3:00, 4:00, 6:00, 7:55, 10:00, 12:00, 15:55, 18:00 hours (h) thereafter on day 1

Population: The PK set (PKS) included all patients in the full analysis set (FAS) with evaluable PK data. FAS included all randomised patients who were dispensed study medication and were documented to have taken at least one dose of study medication.

Maximum measured concentration of Deleobuvir in plasma (Cmax) determined after the first dose.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=9 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Cmax	320 nanogram/millilitre (ng/mL) Geometric Coefficient of Variation 75.0	656 nanogram/millilitre (ng/mL) Geometric Coefficient of Variation 73.1	3500 nanogram/millilitre (ng/mL) Geometric Coefficient of Variation 22.1	4060 nanogram/millilitre (ng/mL) Geometric Coefficient of Variation 70.1	6760 nanogram/millilitre (ng/mL) Geometric Coefficient of Variation 50.6	5730 nanogram/millilitre (ng/mL) Geometric Coefficient of Variation 74.4	9570 nanogram/millilitre (ng/mL) Geometric Coefficient of Variation 35.9	—

SECONDARY outcome

Timeframe: 5 minutes (min) prior to the first dose of study medication and 30 minutes and 1:00, 2:00, 3:00, 4:00, 6:00, 7:55, 10:00, 12:00, 15:55, 18:00 hours (h) thereafter on day 1

Population: PKS

Measured concentration of Deleobuvir in plasma determined immediately before the second dose (Cmin). The number of participants analysed displays the number of participants with available data at the timepoints of interest.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=8 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=8 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=9 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Cmin	105 ng/mL Geometric Coefficient of Variation 83.1	210 ng/mL Geometric Coefficient of Variation 80.6	1190 ng/mL Geometric Coefficient of Variation 39.3	1520 ng/mL Geometric Coefficient of Variation 77.0	3470 ng/mL Geometric Coefficient of Variation 37.7	1800 ng/mL Geometric Coefficient of Variation 65.8	5090 ng/mL Geometric Coefficient of Variation 59.5	—

SECONDARY outcome

Timeframe: 5 minutes (min) prior to the first dose of study medication and 30 minutes and 1:00, 2:00, 3:00, 4:00, 6:00, 7:55, 10:00, 12:00, 15:55, 18:00 hours (h) thereafter on day 1

Population: PKS

Time from dosing to maximum measured concentration (tmax) of Deleobuvir determined after the first dose.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=9 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Tmax	3.00 hours (h) Interval 2.0 to 4.17	3.03 hours (h) Interval 2.03 to 4.0	3.00 hours (h) Interval 2.0 to 4.0	4.00 hours (h) Interval 2.0 to 6.0	6.00 hours (h) Interval 4.0 to 6.0	4.00 hours (h) Interval 2.83 to 6.0	6.00 hours (h) Interval 4.0 to 6.0	—

SECONDARY outcome

Timeframe: 5 minutes (min) prior to the first dose of study medication and 30 minutes and 1:00, 2:00, 3:00, 4:00, 6:00, 7:55, 10:00, 12:00, 15:55, 18:00 hours (h) thereafter on day 1

Population: PKS

Area under the concentration-time curve of Deleobuvir in plasma over the interval 0 hour (h) to the next dose of trial medication (AUC0-τ) measured after first administration of trial drug.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=9 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
AUC0-τ	1410 Nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 77.9	2820 Nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 66.6	15900 Nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 27.3	18600 Nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 62.7	29500 Nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 49.4	23600 Nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 69.5	42400 Nanogramhours/millilitre (ngh/mL) Geometric Coefficient of Variation 42.2	—

SECONDARY outcome

Timeframe: 5 min prior to the first dose of study medication of Day 5; 0:30, 1:00, 2:00, 3:00*, 4:00, 6:00, 8:00*, 10:00, 12:00, 16:00, 24:00, 48:00, 95:55, 96:30, 97:00, 98:00 99:00*, 100:00, 102:00, 104:00*, 106:00, 108:00, 112:00, 120:00, 144:00 h thereafter

Population: PKS

The maximum measured concentration of Deleobuvir in plasma at steady state after the last dose of study drug (Cmax,ss). more detailed time frame information: 5 minutes (min) prior to the first dose of study medication of Day 5 (-0:05) and 0:30, 1:00, 2:00, 3:00\*, 4:00, 6:00, 8:00\*, 10:00, 12:00, 16:00, 24:00, 48:00 h thereafter; Assigned to the planned time points 95:55, 96:30, 97:00, 98:00 99:00\*, 100:00, 102:00, 104:00\*, 106:00, 108:00, 112:00, 120:00, 144:00 h (\*At these time points, in patients with cirrhosis only)

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=8 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=7 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=8 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Cmax,ss	391 ng/mL Geometric Coefficient of Variation 67.8	910 ng/mL Geometric Coefficient of Variation 80.3	3780 ng/mL Geometric Coefficient of Variation 46.3	6780 ng/mL Geometric Coefficient of Variation 76.7	15400 ng/mL Geometric Coefficient of Variation 80.4	9030 ng/mL Geometric Coefficient of Variation 103.0	16500 ng/mL Geometric Coefficient of Variation 66.7	—

SECONDARY outcome

Population: PKS

The minimum measured concentration of Deleobuvir in plasma at steady state (Cmin,ss). more detailed time frame information: 5 minutes (min) prior to the first dose of study medication of Day 5 (-0:05) and 0:30, 1:00, 2:00, 3:00\*, 4:00, 6:00, 8:00\*, 10:00, 12:00, 16:00, 24:00, 48:00 h thereafter; Assigned to the planned time points 95:55, 96:30, 97:00, 98:00 99:00\*, 100:00, 102:00, 104:00\*, 106:00, 108:00, 112:00, 120:00, 144:00 h (\*At these time points, in patients with cirrhosis only). The number of participants analysed displays the number of participants with available data at the timepoints of interest.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=8 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=7 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=7 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Cmin,ss	109 ng/mL Geometric Coefficient of Variation 98.5	201 ng/mL Geometric Coefficient of Variation 90.9	1150 ng/mL Geometric Coefficient of Variation 65.9	2340 ng/mL Geometric Coefficient of Variation 110.0	6920 ng/mL Geometric Coefficient of Variation 93.9	2100 ng/mL Geometric Coefficient of Variation 247.0	6630 ng/mL Geometric Coefficient of Variation 118.0	—

SECONDARY outcome

Population: PKS

Time from dosing to the maximum measured concentration of Deleobuvir at steady state after the last dose of study drug (tmax,ss) more detailed time frame information: 5 minutes (min) prior to the first dose of study medication of Day 5 (-0:05) and 0:30, 1:00, 2:00, 3:00\*, 4:00, 6:00, 8:00\*, 10:00, 12:00, 16:00, 24:00, 48:00 h thereafter; Assigned to the planned time points 95:55, 96:30, 97:00, 98:00 99:00\*, 100:00, 102:00, 104:00\*, 106:00, 108:00, 112:00, 120:00, 144:00 h (\*At these time points, in patients with cirrhosis only)

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=8 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=7 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=8 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Tmax,ss	2.02 h Interval 1.0 to 4.0	4.00 h Interval 1.0 to 6.0	2.52 h Interval 1.0 to 4.0	4.00 h Interval 1.03 to 4.02	4.00 h Interval 0.5 to 4.0	4.00 h Interval 2.0 to 4.0	4.10 h Interval 1.0 to 6.3	—

SECONDARY outcome

Population: PKS

Area under the concentration-time curve of Deleobuvir in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) measured after last dose of trial drug. more detailed time frame information: 5 minutes (min) prior to the first dose of study medication of Day 5 (-0:05) and 0:30, 1:00, 2:00, 3:00\*, 4:00, 6:00, 8:00\*, 10:00, 12:00, 16:00, 24:00, 48:00 h thereafter; Assigned to the planned time points 95:55, 96:30, 97:00, 98:00 99:00\*, 100:00, 102:00, 104:00\*, 106:00, 108:00, 112:00, 120:00, 144:00 h (\*At these time points, in patients with cirrhosis only). The number of participants analysed displays the number of participants with available data at the timepoints of interest.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=8 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=7 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=8 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
AUCτ,ss	1930 ng*h/mL Geometric Coefficient of Variation 79.0	4130 ng*h/mL Geometric Coefficient of Variation 79.1	17900 ng*h/mL Geometric Coefficient of Variation 37.1	36800 ng*h/mL Geometric Coefficient of Variation 82.7	86400 ng*h/mL Geometric Coefficient of Variation 78.1	43500 ng*h/mL Geometric Coefficient of Variation 118.0	88500 ng*h/mL Geometric Coefficient of Variation 83.3	—

SECONDARY outcome

Population: PKS

Area under the concentration-time curve of Deleobuvir in plasma over the interval 0 hour (h) extrapolated to infinity at steady state (AUC0-∞,ss) measured after last administration of trial drug. more detailed time frame information: 5 minutes (min) prior to the first dose of study medication of Day 5 (-0:05) and 0:30, 1:00, 2:00, 3:00\*, 4:00, 6:00, 8:00\*, 10:00, 12:00, 16:00, 24:00, 48:00 h thereafter; Assigned to the planned time points 95:55, 96:30, 97:00, 98:00 99:00\*, 100:00, 102:00, 104:00\*, 106:00, 108:00, 112:00, 120:00, 144:00 h (\*At these time points, in patients with cirrhosis only). The number of participants analysed displays the number of participants with available data at the timepoints of interest.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=8 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=7 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=4 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=7 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
AUC0-∞,ss	2560 ng*h/mL Geometric Coefficient of Variation 91.8	5420 ng*h/mL Geometric Coefficient of Variation 87.6	22800 ng*h/mL Geometric Coefficient of Variation 41.6	54300 ng*h/mL Geometric Coefficient of Variation 110.0	153000 ng*h/mL Geometric Coefficient of Variation 108.0	51700 ng*h/mL Geometric Coefficient of Variation 159.0	129000 ng*h/mL Geometric Coefficient of Variation 119.0	—

SECONDARY outcome

Population: PKS

Terminal rate of Deleobuvir constant in plasma at steady state (λz,ss) measured after last dose of study drug. more detailed time frame information: 5 minutes (min) prior to the first dose of study medication of Day 5 (-0:05) and 0:30, 1:00, 2:00, 3:00\*, 4:00, 6:00, 8:00\*, 10:00, 12:00, 16:00, 24:00, 48:00 h thereafter; Assigned to the planned time points 95:55, 96:30, 97:00, 98:00 99:00\*, 100:00, 102:00, 104:00\*, 106:00, 108:00, 112:00, 120:00, 144:00 h (\*At these time points, in patients with cirrhosis only). The number of participants analysed displays the number of participants with available data at the timepoints of interest.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=8 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=7 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=7 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
λz,ss	0.189 1/h Interval 0.0976 to 0.264	0.180 1/h Interval 0.111 to 0.322	0.131 1/h Interval 0.11 to 0.186	0.117 1/h Interval 0.0869 to 0.209	0.117 1/h Interval 0.11 to 0.124	0.155 1/h Interval 0.115 to 0.273	0.145 1/h Interval 0.118 to 0.163	—

SECONDARY outcome

Population: PKS

Terminal half-life of Deleobuvir in plasma at steady state (t1/2,ss) measured after the last dose of study drug. more detailed time frame information: 5 minutes (min) prior to the first dose of study medication of Day 5 (-0:05) and 0:30, 1:00, 2:00, 3:00\*, 4:00, 6:00, 8:00\*, 10:00, 12:00, 16:00, 24:00, 48:00 h thereafter; Assigned to the planned time points 95:55, 96:30, 97:00, 98:00 99:00\*, 100:00, 102:00, 104:00\*, 106:00, 108:00, 112:00, 120:00, 144:00 h (\*At these time points, in patients with cirrhosis only). The number of participants analysed displays the number of participants with available data at the timepoints of interest.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=8 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=7 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=7 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
t1/2,ss	3.67 h Interval 2.63 to 7.1	3.84 h Interval 2.15 to 6.24	5.31 h Interval 3.73 to 6.33	5.90 h Interval 3.32 to 7.98	5.95 h Interval 5.59 to 6.28	4.48 h Interval 2.54 to 6.02	4.79 h Interval 4.24 to 5.85	—

SECONDARY outcome

Population: PKS

Apparent clearance of Deleobuvir in plasma after oral administration at steady state (CL/F,ss) measured after the last dose of study drug. more detailed time frame information: 5 minutes (min) prior to the first dose of study medication of Day 5 (-0:05) and 0:30, 1:00, 2:00, 3:00\*, 4:00, 6:00, 8:00\*, 10:00, 12:00, 16:00, 24:00, 48:00 h thereafter; Assigned to the planned time points 95:55, 96:30, 97:00, 98:00 99:00\*, 100:00, 102:00, 104:00\*, 106:00, 108:00, 112:00, 120:00, 144:00 h (\*At these time points, in patients with cirrhosis only). The number of participants analysed displays the number of participants with available data at the timepoints of interest.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=8 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=7 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=7 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
CL/F,ss	865 Millilitre per minute (mL/min) Geometric Coefficient of Variation 79.0	806 Millilitre per minute (mL/min) Geometric Coefficient of Variation 79.1	372 Millilitre per minute (mL/min) Geometric Coefficient of Variation 37.1	181 Millilitre per minute (mL/min) Geometric Coefficient of Variation 82.7	116 Millilitre per minute (mL/min) Geometric Coefficient of Variation 78.1	319 Millilitre per minute (mL/min) Geometric Coefficient of Variation 132.0	226 Millilitre per minute (mL/min) Geometric Coefficient of Variation 83.3	—

SECONDARY outcome

Population: PKS

Apparent volume of Deleobuvir distribution during the terminal phase λz following an oral dose at steady state (Vz/F,ss) after the last dose of study drug. more detailed time frame information: 5 minutes (min) prior to the first dose of study medication of Day 5 (-0:05) and 0:30, 1:00, 2:00, 3:00\*, 4:00, 6:00, 8:00\*, 10:00, 12:00, 16:00, 24:00, 48:00 h thereafter; Assigned to the planned time points 95:55, 96:30, 97:00, 98:00 99:00\*, 100:00, 102:00, 104:00\*, 106:00, 108:00, 112:00, 120:00, 144:00 h (\*At these time points, in patients with cirrhosis only). The number of participants analysed displays the number of participants with available data at the timepoints of interest.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=8 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=7 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=7 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Vz/F,ss	279 Litre (L) Geometric Coefficient of Variation 53.1	254 Litre (L) Geometric Coefficient of Variation 49.8	164 Litre (L) Geometric Coefficient of Variation 41.4	83.9 Litre (L) Geometric Coefficient of Variation 58.2	59.7 Litre (L) Geometric Coefficient of Variation 72.8	110 Litre (L) Geometric Coefficient of Variation 108.0	96.8 Litre (L) Geometric Coefficient of Variation 86.5	—

SECONDARY outcome

Timeframe: up to day 7

Population: The full analysis set (FAS) included all randomised patients who were dispensed study medication and were documented to have taken at least one dose of study medication.

Individual drug plasma concentrations of Deleobuvir after multiple oral administration. Within the categories PTM means planned time. The number of participants analysed displays the number of participants included in the analysis data set whereas the number of participants for each timepoint displays the number of participants with available data at that timepoint. Below the limit of quantification (BLQ) is abbreviated.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=9 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=9 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Plasma Concentration Time Profiles PTM 100 hours; N(per Arm)=9/9/8/7/5/8/10)	329 ng/mL Geometric Coefficient of Variation 86.9	658 ng/mL Geometric Coefficient of Variation 109.0	2790 ng/mL Geometric Coefficient of Variation 50.2	6210 ng/mL Geometric Coefficient of Variation 89.9	14800 ng/mL Geometric Coefficient of Variation 86.7	7740 ng/mL Geometric Coefficient of Variation 107.0	14000 ng/mL Geometric Coefficient of Variation 74.7	—
Plasma Concentration Time Profiles PTM 106 hours; N(per Arm)=9/9/8/7/5/7/10)	76.2 ng/mL Geometric Coefficient of Variation 121.0	158 ng/mL Geometric Coefficient of Variation 115.0	553 ng/mL Geometric Coefficient of Variation 74.8	1720 ng/mL Geometric Coefficient of Variation 153.0	5260 ng/mL Geometric Coefficient of Variation 115.0	1200 ng/mL Geometric Coefficient of Variation 316.0	4370 ng/mL Geometric Coefficient of Variation 190.0	—
Plasma Concentration Time Profiles PTM 108 hours; N(per Arm)=9/9/8/7/5/7/10)	52.5 ng/mL Geometric Coefficient of Variation 136.0	92.7 ng/mL Geometric Coefficient of Variation 136.0	321 ng/mL Geometric Coefficient of Variation 79.0	1160 ng/mL Geometric Coefficient of Variation 171.0	4040 ng/mL Geometric Coefficient of Variation 120.0	681 ng/mL Geometric Coefficient of Variation 403.0	2780 ng/mL Geometric Coefficient of Variation 314.0	—
Plasma Concentration Time Profiles PTM 112 hours; N(per Arm)=9/9/8/7/5/7/10)	20.8 ng/mL Geometric Coefficient of Variation 138.0	39.9 ng/mL Geometric Coefficient of Variation 157.0	153 ng/mL Geometric Coefficient of Variation 82.6	553 ng/mL Geometric Coefficient of Variation 211.0	1890 ng/mL Geometric Coefficient of Variation 130.0	239 ng/mL Geometric Coefficient of Variation 436.0	1110 ng/mL Geometric Coefficient of Variation 444.0	—
Plasma Concentration Time Profiles PTM 120 hours; N(per Arm)= 5/6/8/ 7/5/7/10)	NA ng/mL Geometric Coefficient of Variation NA 4 of 9 samples below limit of quantification (BLQ). 5 values were reportable (5 of 9 = total N of 55.6%), no descriptive statistics calculated. A total N of 66.7 % (2/3) of reportable values is needed.	20.2 ng/mL Geometric Coefficient of Variation 126.0	59.0 ng/mL Geometric Coefficient of Variation 75.9	219 ng/mL Geometric Coefficient of Variation 269.0	699 ng/mL Geometric Coefficient of Variation 185.0	67.2 ng/mL Geometric Coefficient of Variation 384.0	316 ng/mL Geometric Coefficient of Variation 512.0	—
Plasma Concentration Time Profiles PTM 144 hours; N(per Arm)= 1/1/5/ 5/5/4/10)	NA ng/mL Geometric Coefficient of Variation NA 8 of 9 samples BLQ, no descriptive statistics calculated	NA ng/mL Geometric Coefficient of Variation NA 8 of 9 samples BLQ, no descriptive statistics calculated	NA ng/mL Geometric Coefficient of Variation NA 3 of 9 samples BLQ. Another subject did not have PK sampling past 48 hours. 5 values were reportable (5 of 9 = total N of 55.6%), no descriptive statistics calculated. A total N of 66.7 % (2/3) of reportable values is needed.	36.2 ng/mL Geometric Coefficient of Variation 272.0	56.2 ng/mL Geometric Coefficient of Variation 186.0	NA ng/mL Geometric Coefficient of Variation NA 3 of 9 samples BLQ and another sample excluded, no descriptive statistics calculated	20.1 ng/mL Geometric Coefficient of Variation 175.0	—
Plasma Concentration Time Profiles PTM 0.5 hours; N(per Arm)=6/6/7/8/3/5/9)	54.6 ng/mL Geometric Coefficient of Variation 328.0	15.1 ng/mL Geometric Coefficient of Variation 57.7	163 ng/mL Geometric Coefficient of Variation 214.0	45.4 ng/mL Geometric Coefficient of Variation 632.0	NA ng/mL Geometric Coefficient of Variation NA 2 of 5 samples BLQ, no descriptive statistics calculated	NA ng/mL Geometric Coefficient of Variation NA 4 of 9 samples BLQ, no descriptive statistics calculated	124 ng/mL Geometric Coefficient of Variation 1250.0	—
Plasma Concentration Time Profiles PTM 1 hour; N(per Arm)=7/9/9/8/5/8/10)	91.4 ng/mL Geometric Coefficient of Variation 111.0	53.0 ng/mL Geometric Coefficient of Variation 387.0	427 ng/mL Geometric Coefficient of Variation 569.0	597 ng/mL Geometric Coefficient of Variation 168.0	177 ng/mL Geometric Coefficient of Variation 258.0	519 ng/mL Geometric Coefficient of Variation 570.0	647 ng/mL Geometric Coefficient of Variation 275.0	—
Plasma Concentration Time Profiles PTM 2 hours; N(per Arm)=9/9/9/8/5/9/10)	208 ng/mL Geometric Coefficient of Variation 199.0	246 ng/mL Geometric Coefficient of Variation 133.0	2290 ng/mL Geometric Coefficient of Variation 70.8	1720 ng/mL Geometric Coefficient of Variation 62.4	1390 ng/mL Geometric Coefficient of Variation 112.0	1650 ng/mL Geometric Coefficient of Variation 240.0	1780 ng/mL Geometric Coefficient of Variation 208.0	—
Plasma Concentration Time Profiles PTM 3 hours; N(per Arm)=9/9/9/8/5/9/10)	162 ng/mL Geometric Coefficient of Variation 213.0	476 ng/mL Geometric Coefficient of Variation 74.9	2830 ng/mL Geometric Coefficient of Variation 41.8	2950 ng/mL Geometric Coefficient of Variation 50.1	3330 ng/mL Geometric Coefficient of Variation 89.9	3750 ng/mL Geometric Coefficient of Variation 106.0	4330 ng/mL Geometric Coefficient of Variation 110.0	—
Plasma Concentration Time Profiles PTM 4 hours; N(per Arm)=9/9/9/8/5/9/10)	274 ng/mL Geometric Coefficient of Variation 70.0	574 ng/mL Geometric Coefficient of Variation 73.8	2800 ng/mL Geometric Coefficient of Variation 35.6	3740 ng/mL Geometric Coefficient of Variation 70.4	5060 ng/mL Geometric Coefficient of Variation 83.2	4920 ng/mL Geometric Coefficient of Variation 78.0	6930 ng/mL Geometric Coefficient of Variation 64.9	—
Plasma Concentration Time Profiles PTM 6 hours; N(per Arm)=9/8/9/8/5/9/10)	181 ng/mL Geometric Coefficient of Variation 69.5	377 ng/mL Geometric Coefficient of Variation 57.6	2030 ng/mL Geometric Coefficient of Variation 42.9	2760 ng/mL Geometric Coefficient of Variation 89.7	6250 ng/mL Geometric Coefficient of Variation 57.4	3350 ng/mL Geometric Coefficient of Variation 75.0	8890 ng/mL Geometric Coefficient of Variation 34.6	—
Plasma Concentration Time Profiles PTM 7.917 hours; N(per Arm)=8/8/9/8/5/9/10)	105 ng/mL Geometric Coefficient of Variation 83.1	210 ng/mL Geometric Coefficient of Variation 80.6	1190 ng/mL Geometric Coefficient of Variation 39.3	1520 ng/mL Geometric Coefficient of Variation 77.0	3470 ng/mL Geometric Coefficient of Variation 37.7	1800 ng/mL Geometric Coefficient of Variation 65.8	5090 ng/mL Geometric Coefficient of Variation 59.5	—
Plasma Concentration Time Profiles PTM 10 hours; N(per Arm)=9/9/9/8/5/9/10)	282 ng/mL Geometric Coefficient of Variation 88.7	646 ng/mL Geometric Coefficient of Variation 170.0	4170 ng/mL Geometric Coefficient of Variation 93.7	2580 ng/mL Geometric Coefficient of Variation 79.7	5770 ng/mL Geometric Coefficient of Variation 88.6	4120 ng/mL Geometric Coefficient of Variation 75.4	9720 ng/mL Geometric Coefficient of Variation 48.9	—
Plasma Concentration Time Profiles PTM 12 hours; N(per Arm)=9/9/9/8/5/9/10)	161 ng/mL Geometric Coefficient of Variation 66.2	769 ng/mL Geometric Coefficient of Variation 92.8	3300 ng/mL Geometric Coefficient of Variation 31.5	3500 ng/mL Geometric Coefficient of Variation 74.8	7340 ng/mL Geometric Coefficient of Variation 49.6	7290 ng/mL Geometric Coefficient of Variation 48.2	12700 ng/mL Geometric Coefficient of Variation 68.1	—
Plasma Concentration Time Profiles PTM 15.917 hours; N(per Arm)=9/9/9/7/5/9/10)	73.7 ng/mL Geometric Coefficient of Variation 101.0	222 ng/mL Geometric Coefficient of Variation 90.5	1180 ng/mL Geometric Coefficient of Variation 32.7	1600 ng/mL Geometric Coefficient of Variation 76.1	5230 ng/mL Geometric Coefficient of Variation 49.2	2220 ng/mL Geometric Coefficient of Variation 96.1	5120 ng/mL Geometric Coefficient of Variation 112.0	—
Plasma Concentration Time Profiles PTM 18 hours; N(per Arm)=9/9/9/8/5/9/10)	265 ng/mL Geometric Coefficient of Variation 69.7	379 ng/mL Geometric Coefficient of Variation 155.0	2520 ng/mL Geometric Coefficient of Variation 82.6	2870 ng/mL Geometric Coefficient of Variation 97.5	5340 ng/mL Geometric Coefficient of Variation 67.9	3060 ng/mL Geometric Coefficient of Variation 165.0	8100 ng/mL Geometric Coefficient of Variation 108.0	—
Plasma Concentration Time Profiles PTM 23.917 hours; N(per Arm)=9/9/9/7/5/9/10)	164 ng/mL Geometric Coefficient of Variation 98.1	531 ng/mL Geometric Coefficient of Variation 78.1	2290 ng/mL Geometric Coefficient of Variation 48.8	3570 ng/mL Geometric Coefficient of Variation 113.0	7690 ng/mL Geometric Coefficient of Variation 61.5	4840 ng/mL Geometric Coefficient of Variation 91.4	13800 ng/mL Geometric Coefficient of Variation 64.8	—
Plasma Concentration Time Profiles PTM 47.917 hours; N(per Arm)=9/9/9/7/5/9/10)	154 ng/mL Geometric Coefficient of Variation 81.4	403 ng/mL Geometric Coefficient of Variation 96.6	2200 ng/mL Geometric Coefficient of Variation 32.6	3490 ng/mL Geometric Coefficient of Variation 119.0	9200 ng/mL Geometric Coefficient of Variation 83.6	4680 ng/mL Geometric Coefficient of Variation 157.0	12000 ng/mL Geometric Coefficient of Variation 89.1	—
Plasma Concentration Time Profiles PTM 71.917 hours; N(per Arm)=9/9/8/7/5/9/10)	164 ng/mL Geometric Coefficient of Variation 98.0	378 ng/mL Geometric Coefficient of Variation 70.7	1670 ng/mL Geometric Coefficient of Variation 40.6	3420 ng/mL Geometric Coefficient of Variation 90.0	11500 ng/mL Geometric Coefficient of Variation 77.2	3170 ng/mL Geometric Coefficient of Variation 219.0	9440 ng/mL Geometric Coefficient of Variation 202.0	—
Plasma Concentration Time Profiles PTM 95.917 hours; N(per Arm)=9/9/8/7/5/9/10)	158 ng/mL Geometric Coefficient of Variation 93.7	383 ng/mL Geometric Coefficient of Variation 88.7	1880 ng/mL Geometric Coefficient of Variation 34.0	2820 ng/mL Geometric Coefficient of Variation 86.8	5600 ng/mL Geometric Coefficient of Variation 192.0	3120 ng/mL Geometric Coefficient of Variation 224.0	7820 ng/mL Geometric Coefficient of Variation 133.0	—
Plasma Concentration Time Profiles PTM 96.5 hours; N(per Arm)=9/9/8/7/5/9/10)	149 ng/mL Geometric Coefficient of Variation 90.6	366 ng/mL Geometric Coefficient of Variation 84.7	1830 ng/mL Geometric Coefficient of Variation 51.1	3220 ng/mL Geometric Coefficient of Variation 85.0	8360 ng/mL Geometric Coefficient of Variation 92.7	3330 ng/mL Geometric Coefficient of Variation 181.0	7840 ng/mL Geometric Coefficient of Variation 114.0	—
Plasma Concentration Time Profiles PTM 97 hours; N(per Arm)=9/9/8/7/5/9/9)	209 ng/mL Geometric Coefficient of Variation 88.4	427 ng/mL Geometric Coefficient of Variation 86.0	2400 ng/mL Geometric Coefficient of Variation 56.7	3610 ng/mL Geometric Coefficient of Variation 76.3	8510 ng/mL Geometric Coefficient of Variation 73.9	4350 ng/mL Geometric Coefficient of Variation 142.0	9460 ng/mL Geometric Coefficient of Variation 118.0	—
Plasma Concentration Time Profiles PTM 98 hours; N(per Arm)=9/9/8/7/5/9/10)	313 ng/mL Geometric Coefficient of Variation 64.3	503 ng/mL Geometric Coefficient of Variation 105.0	2760 ng/mL Geometric Coefficient of Variation 49.7	4620 ng/mL Geometric Coefficient of Variation 77.0	10000 ng/mL Geometric Coefficient of Variation 74.3	7390 ng/mL Geometric Coefficient of Variation 118.0	11400 ng/mL Geometric Coefficient of Variation 86.7	—
Plasma Concentration Time Profiles PTM 99 hours; N(per Arm)=9/9/8/7/5/8/10)	300 ng/mL Geometric Coefficient of Variation 70.4	565 ng/mL Geometric Coefficient of Variation 108.0	2820 ng/mL Geometric Coefficient of Variation 37.2	5120 ng/mL Geometric Coefficient of Variation 93.5	11200 ng/mL Geometric Coefficient of Variation 79.5	7990 ng/mL Geometric Coefficient of Variation 94.2	12200 ng/mL Geometric Coefficient of Variation 72.9	—
Plasma Concentration Time Profiles PTM 102 hours; N(per Arm)=9/9/8/7/5/8/10)	199 ng/mL Geometric Coefficient of Variation 92.7	492 ng/mL Geometric Coefficient of Variation 99.4	1630 ng/mL Geometric Coefficient of Variation 70.6	4600 ng/mL Geometric Coefficient of Variation 102.0	11400 ng/mL Geometric Coefficient of Variation 76.6	4450 ng/mL Geometric Coefficient of Variation 144.0	11200 ng/mL Geometric Coefficient of Variation 91.6	—
Plasma Concentration Time Profiles PTM 104 hours; N(per Arm)=9/9/8/7/5/7/10)	124 ng/mL Geometric Coefficient of Variation 113.0	254 ng/mL Geometric Coefficient of Variation 109.0	867 ng/mL Geometric Coefficient of Variation 73.1	2710 ng/mL Geometric Coefficient of Variation 119.0	7450 ng/mL Geometric Coefficient of Variation 91.5	2230 ng/mL Geometric Coefficient of Variation 222.0	6830 ng/mL Geometric Coefficient of Variation 150.0	—

SECONDARY outcome

Timeframe: Baseline, up to day 14

Population: The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.

Number of patients with clinically significant changes in vital signs (pulse rate, systolic and diastolic blood pressure) presents the number of patients with an reported adverse event which has a symptom in changes in vital signs. Vascular disorders was identified as changes in vital signs. The number of participant with vascular disorders is presented in this outcome measure

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=9 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=5 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis n=10 Participants DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Number of Patients With Clinically Significant Changes in Vital Signs (Pulse Rate, Systolic and Diastolic Blood Pressure).	1 participants	1 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: up to 14 days

Population: Treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation. Only patients included having no missing ECG measurements .

Number of patients with a new onset of an abnormal finding by central assessment are presented.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=16 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=9 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Number of Patients With Abnormal Findings in 12-lead ECG (Electrocardiogram) U-wave	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	—
Number of Patients With Abnormal Findings in 12-lead ECG (Electrocardiogram) None	13 participants	9 participants	9 participants	12 participants	5 participants	8 participants	7 participants	—
Number of Patients With Abnormal Findings in 12-lead ECG (Electrocardiogram) Sinus rhythm	1 participants	0 participants	0 participants	3 participants	0 participants	1 participants	2 participants	—
Number of Patients With Abnormal Findings in 12-lead ECG (Electrocardiogram) Conduction	1 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	—
Number of Patients With Abnormal Findings in 12-lead ECG (Electrocardiogram) Morphology	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	—
Number of Patients With Abnormal Findings in 12-lead ECG (Electrocardiogram) Myocardial infarction	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	—
Number of Patients With Abnormal Findings in 12-lead ECG (Electrocardiogram) ST segment	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	—
Number of Patients With Abnormal Findings in 12-lead ECG (Electrocardiogram) T-wave	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Baseline, up to day 14

Number of patients with abnormal changes in safety laboratory tests including urine protein diagnostics, and adrenocorticotropic hormone (ACTH) and cortisol measurements resulted in adverse events.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=9 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=5 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis n=10 Participants DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Number of Patients With Abnormal Changes in Laboratory Tests	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: up to 14 days

Number of patients with any adverse event (AE)

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=9 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=5 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis n=10 Participants DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Number of Patients With Adverse Events	4 participants	2 participants	3 participants	7 participants	5 participants	4 participants	6 participants	9 participants

SECONDARY outcome

Timeframe: up to day 14

The number of patients with abnormal findings in physical examination presents the number of patients with any treatment-emergent adverse events in this study.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=9 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=8 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=5 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis n=10 Participants DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Number of Patients With Abnormal Findings in Physical Examination	4 participants	2 participants	3 participants	7 participants	5 participants	4 participants	6 participants	9 participants

SECONDARY outcome

Timeframe: day 6

The global tolerability was presented on a four item scale: good, satisfactory, not satisfactory and bad. Rating was done by the investigator.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=17 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=9 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Assessment of Global Tolerability on a 4-point Scale Good	11 participants	9 participants	8 participants	12 participants	4 participants	8 participants	9 participants	—
Assessment of Global Tolerability on a 4-point Scale Bad	0 participants	0 participants	0 participants	0 participants	0 participants	1 participants	0 participants	—
Assessment of Global Tolerability on a 4-point Scale Satisfactory	3 participants	0 participants	1 participants	3 participants	1 participants	0 participants	1 participants	—
Assessment of Global Tolerability on a 4-point Scale Not satisfactory	0 participants	0 participants	0 participants	2 participants	0 participants	0 participants	0 participants	—

SECONDARY outcome

Timeframe: Visit 1, Visit 7

Population: Treated set.

The body temperature will be presented as the mean values in visit 1 and visit 7. The number of participants analysed displays the number of participants included in the analysis set whereas the numbers for each timepoint display the number of participants with available data at that timepoint.

Outcome measures

Outcome measures
Measure	Placebo Fibrosis n=14 Participants Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 Participants DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 Participants DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=17 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=5 Participants DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=9 Participants DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=10 Participants DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Body Temperature Visit 7 (N=13/9/9/15/5/8/10)	36.400 degree (°C) Standard Deviation 0.283	36.656 degree (°C) Standard Deviation 0.403	36.156 degree (°C) Standard Deviation 0.265	36.307 degree (°C) Standard Deviation 0.451	35.540 degree (°C) Standard Deviation 0.445	36.125 degree (°C) Standard Deviation 0.287	36.320 degree (°C) Standard Deviation 0.744	—
Body Temperature Visit 1 (N=7/5/8/14/5/7/6)	36.429 degree (°C) Standard Deviation 0.287	36.780 degree (°C) Standard Deviation 0.455	36.513 degree (°C) Standard Deviation 0.557	36.550 degree (°C) Standard Deviation 0.641	35.760 degree (°C) Standard Deviation 0.709	36.686 degree (°C) Standard Deviation 0.248	36.517 degree (°C) Standard Deviation 0.567	—

Adverse Events

Placebo Fibrosis

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

DBV 100mg Fibrosis

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

DBV 200mg Fibrosis

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

DBV 400mg Fibrosis

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

DBV 400mg Cirrhosis

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

DBV 600mg Cirrhosis

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

DBV 800mg Fibrosis

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

DBV 1200mg Fibrosis

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo Fibrosis n=14 participants at risk Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 participants at risk DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 participants at risk DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=9 participants at risk DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=8 participants at risk DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=5 participants at risk DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 participants at risk DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis n=10 participants at risk DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.

Other adverse events

Other adverse events
Measure	Placebo Fibrosis n=14 participants at risk Placebo (as tablet, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 100mg Fibrosis n=9 participants at risk DBV 100mg (as tablet, 2x 50mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 200mg Fibrosis n=9 participants at risk DBV 200mg (as tablet, 1x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Fibrosis n=9 participants at risk DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 400mg Cirrhosis n=8 participants at risk DBV 400mg (as tablet, 2x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 600mg Cirrhosis n=5 participants at risk DBV 600mg (as tablet, 3x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with cirrhosis	DBV 800mg Fibrosis n=9 participants at risk DBV 800mg (as tablet, 4x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis	DBV 1200mg Fibrosis n=10 participants at risk DBV 1200mg (as tablet, 6x 200mg, oral) administered 3 times (every 8 hours) daily after a meal for 5 days in patients with fibrosis
Cardiac disorders Cardiovascular disorder	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Ear and labyrinth disorders Ear pain	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	12.5% 1/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Ear and labyrinth disorders Tinnitus	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	10.0% 1/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Abdominal distension	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	10.0% 1/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Abdominal pain	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	10.0% 1/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Diarrhoea	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	22.2% 2/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 1/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	70.0% 7/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Eructation	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Faeces pale	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Flatulence	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	22.2% 2/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Frequent bowel movements	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	12.5% 1/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	10.0% 1/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Haemorrhoids	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Lip disorder	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Nausea	14.3% 2/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	22.2% 2/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	40.0% 2/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 2/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Gastrointestinal disorders Vomiting	7.1% 1/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	40.0% 2/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
General disorders Asthenia	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	12.5% 1/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 1/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
General disorders Fatigue	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	22.2% 2/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	30.0% 3/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
General disorders Gait disturbance	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
General disorders Influenza like illness	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 1/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
General disorders Irritability	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
General disorders Pain	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	10.0% 1/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
General disorders Pyrexia	7.1% 1/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Investigations Electrocardiogram QT prolonged	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	12.5% 1/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Investigations Urine colour abnormal	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 1/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	12.5% 1/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Musculoskeletal and connective tissue disorders Myalgia	14.3% 2/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Nervous system disorders Dizziness	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	12.5% 1/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Nervous system disorders Dysgeusia	7.1% 1/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Nervous system disorders Headache	21.4% 3/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	22.2% 2/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 1/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	22.2% 2/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 2/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Nervous system disorders Hyperaesthesia	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	30.0% 3/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Nervous system disorders Paraesthesia	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	12.5% 1/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 2/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Psychiatric disorders Anxiety	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Psychiatric disorders Insomnia	7.1% 1/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 1/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Psychiatric disorders Stress	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 1/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	40.0% 4/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 1/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	10.0% 1/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Skin and subcutaneous tissue disorders Rash	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	20.0% 2/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Skin and subcutaneous tissue disorders Skin burning sensation	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Skin and subcutaneous tissue disorders Skin swelling	0.00% 0/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.
Vascular disorders Hypertension	7.1% 1/14 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	11.1% 1/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/8 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/5 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/9 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.	0.00% 0/10 • Assessment of adverse events from the baseline up to 14 days The treated set (TS) included all patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomisation.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER