Download PDF

Clinical Trial Results:
A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, ACH-3102, and Simeprevir

Summary
EudraCT number	2016-002845-46
Trial protocol	GB
Global end of trial date	11 May 2018

Results information
Results version number	v1(current)
This version publication date	26 May 2019
First version publication date	26 May 2019
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

AL-335-604

ISRCTN number

US NCT number

NCT02569710

WHO universal trial number (UTN)

Sponsor organisation name

Alios BioPharm

Sponsor organisation address

260 E. Grand Ave, South San Francisco CA, United States, 94080

Public contact

Clinical Registry group, Alios BioPharma, swang162@ITS.JNJ.com

Scientific contact

Clinical Registry group, Alios BioPharma, swang162@ITS.JNJ.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 May 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

11 May 2018

Global end of trial reached?

Yes

Global end of trial date

11 May 2018

Was the trial ended prematurely?

Main objective of the trial

The primary purpose of the study is to evaluate the safety and tolerability of AL-335 in combination with Odalasvir (ODV) with or without Simeprevir (SMV) in subjects with chronic Genotype (GT)1 or GT2 or GT3 Hepatitis C virus (HCV) infection.

Protection of trial subjects

This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with good clinical practices and applicable regulatory requirements. Safety was evaluated throughout the study and included adverse events (AEs), vital signs, laboratory assessments (chemistry, hematology, urinalysis, and pregnancy tests), 12-lead electrocardiogram (ECG), and physical examination.

Background therapy

Evidence for comparator

Actual start date of recruitment

31 Oct 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Moldova, Republic of: 16

Country: Number of subjects enrolled

Mauritius: 8

Country: Number of subjects enrolled

New Zealand: 134

Country: Number of subjects enrolled

United Kingdom: 3

Worldwide total number of subjects

161

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

154

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

No subjects were recruited for Cohorts 10 and 12, hence no data is reported here for these two cohorts.

Screening details

A total of 161 subjects were randomized, 112 in subjects without cirrhosis and 49 in subjects with cirrhosis.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1 (8 Weeks Genotype [GT1])

Arm description

Cohort 1 (Subjects without Cirrhosis) received single dose of AL-335 400 milligrams (mg) tablets once daily (QD), odalasvir (ODV) 50 mg tablet and simeprevir 100 mg tablet QD for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

AL-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 400 mg tablets QD.

Investigational medicinal product name

Simeprevir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Simeprevir tablets 100 mg QD.

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 50 mg tablets QD.

Cohort 1b + Cohort 4 (8 Weeks GT1)

Arm description

Cohort 1b (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD and ODV 50 mg tablets every other day (QOD) for 8 weeks; Cohort 4 (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD and ODV 50 mg tablets QOD for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

AL-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 800 mg tablets QD.

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 50 mg tablets QOD.

Cohort 2 (8 Weeks GT1)

Arm description

Cohort 2 (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Al-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 800 mg tablets QD.

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 50 mg tablets QOD.

Investigational medicinal product name

Simeprevir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Simeprevir 75 mg tablets QD.

Cohort 3 (Subjects with Cirrhosis)

Arm description

Cohort 3 (Subjects with Cirrhosis) received single dose of AL-335 800 mg QD, ODV 50 mg QOD and SMV 75 mg QD for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

AL-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 800 mg tablets QD.

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 50 mg tablets QOD.

Investigational medicinal product name

Simeprevir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Simeprevir 75 mg tablets QD.

Cohort 4 (12 Weeks GT1)

Arm description

Cohort 4 (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD and ODV 50 mg tablets QOD for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 50 mg tablets QOD.

Investigational medicinal product name

AL-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 800 mg tablets QD.

Cohort 5a (8 Weeks GT3)

Arm description

Cohort 5a (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

AL-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 800 mg tablets QD.

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 50 mg tablets QOD.

Investigational medicinal product name

Simeprevir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Simeprevir 75 mg tablets QD.

Cohort 5b (12 Weeks GT3)

Arm description

Cohort 5b (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

AL-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 800 mg tablets QD.

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 50 mg tablets QOD.

Investigational medicinal product name

Simeprevir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Simeprevir 75 mg tablets QD.

Cohort 6,7,8 (8 Weeks GT1 F4)

Arm description

Cohort 6 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 8 weeks; Cohort 7 and Cohort 8 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 25 mg tablets QD and SMV 75 mg tablets QD for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

AL-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 800 mg tablets QD.

Investigational medicinal product name

Simeprevir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Simeprevir 75 mg tablets QD.

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 50 mg tablets QOD.

Cohort 9 (12 Weeks GT1 F4)

Arm description

Cohort 9 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 25 mg tablets QD and SMV 75 mg tablets QD for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

AL-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 800 mg tablets QD.

Investigational medicinal product name

Simeprevir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Simeprevir tablets 75 mg QD.

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 25 mg tablets QD.

Cohort 11 (12 Weeks GT2 F4)

Arm description

Cohort 11 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 25 mg tablets QD and SMV 75 mg tablets QD for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Al-335

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received AL-335 800 mg tablets QD.

Investigational medicinal product name

Simeprevir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Simeprevir 75 mg tablets QD.

Investigational medicinal product name

Odalasvir

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received Odalasvir 25 mg tablets QD.

Number of subjects in period 1	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Started	20	25	20	20	8	5	14	30	15	4
Completed	19	25	20	20	7	4	12	29	14	4
Not completed	1	0	0	0	1	1	2	1	1	0
Consent withdrawn by subject	-	-	-	-	-	1	-	-	-	-
Adverse event, non-fatal	1	-	-	-	-	-	-	-	-	-
Other	-	-	-	-	1	-	1	1	-	-
Lost to follow-up	-	-	-	-	-	-	1	-	1	-

Baseline characteristics

Top of page

Reporting group title

Cohort 1 (8 Weeks Genotype [GT1])

Reporting group description

Cohort 1 (Subjects without Cirrhosis) received single dose of AL-335 400 milligrams (mg) tablets once daily (QD), odalasvir (ODV) 50 mg tablet and simeprevir 100 mg tablet QD for 8 weeks.

Reporting group title

Cohort 1b + Cohort 4 (8 Weeks GT1)

Reporting group description

Reporting group title

Cohort 2 (8 Weeks GT1)

Reporting group description

Cohort 2 (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 8 weeks.

Reporting group title

Cohort 3 (Subjects with Cirrhosis)

Reporting group description

Cohort 3 (Subjects with Cirrhosis) received single dose of AL-335 800 mg QD, ODV 50 mg QOD and SMV 75 mg QD for 8 weeks.

Reporting group title

Cohort 4 (12 Weeks GT1)

Reporting group description

Cohort 4 (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD and ODV 50 mg tablets QOD for 12 weeks.

Reporting group title

Cohort 5a (8 Weeks GT3)

Reporting group description

Cohort 5a (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 8 weeks.

Reporting group title

Cohort 5b (12 Weeks GT3)

Reporting group description

Cohort 5b (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 12 weeks.

Reporting group title

Cohort 6,7,8 (8 Weeks GT1 F4)

Reporting group description

Reporting group title

Cohort 9 (12 Weeks GT1 F4)

Reporting group description

Cohort 9 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 25 mg tablets QD and SMV 75 mg tablets QD for 12 weeks.

Reporting group title

Cohort 11 (12 Weeks GT2 F4)

Reporting group description

Cohort 11 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 25 mg tablets QD and SMV 75 mg tablets QD for 12 weeks.

Reporting group values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)	Total
Number of subjects	20	25	20	20	8	5	14	30	15	4	161
Title for AgeCategorical
Units: subjects
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	20	25	20	20	8	5	13	27	14	2	154
From 65 to 84 years	0	0	0	0	0	0	1	3	1	2	7
85 years and over	0	0	0	0	0	0	0	0	0	0	0
Title for AgeContinuous
Units: years
median (full range (min-max))	56 (30 to 61)	55 (29 to 64)	56 (36 to 62)	55.5 (30 to 64)	55 (41 to 60)	54 (38 to 64)	44.5 (18 to 65)	56.5 (37 to 68)	52 (36 to 67)	63.5 (61 to 69)	-
Title for Gender
Units: subjects
Female	7	8	6	8	5	0	1	16	2	1	54
Male	13	17	14	12	3	5	13	14	13	3	107

End points

Top of page

Reporting group title

Cohort 1 (8 Weeks Genotype [GT1])

Reporting group description

Cohort 1 (Subjects without Cirrhosis) received single dose of AL-335 400 milligrams (mg) tablets once daily (QD), odalasvir (ODV) 50 mg tablet and simeprevir 100 mg tablet QD for 8 weeks.

Reporting group title

Cohort 1b + Cohort 4 (8 Weeks GT1)

Reporting group description

Reporting group title

Cohort 2 (8 Weeks GT1)

Reporting group description

Cohort 2 (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 8 weeks.

Reporting group title

Cohort 3 (Subjects with Cirrhosis)

Reporting group description

Cohort 3 (Subjects with Cirrhosis) received single dose of AL-335 800 mg QD, ODV 50 mg QOD and SMV 75 mg QD for 8 weeks.

Reporting group title

Cohort 4 (12 Weeks GT1)

Reporting group description

Cohort 4 (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD and ODV 50 mg tablets QOD for 12 weeks.

Reporting group title

Cohort 5a (8 Weeks GT3)

Reporting group description

Cohort 5a (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 8 weeks.

Reporting group title

Cohort 5b (12 Weeks GT3)

Reporting group description

Cohort 5b (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 12 weeks.

Reporting group title

Cohort 6,7,8 (8 Weeks GT1 F4)

Reporting group description

Reporting group title

Cohort 9 (12 Weeks GT1 F4)

Reporting group description

Cohort 9 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 25 mg tablets QD and SMV 75 mg tablets QD for 12 weeks.

Reporting group title

Cohort 11 (12 Weeks GT2 F4)

Reporting group description

Cohort 11 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 25 mg tablets QD and SMV 75 mg tablets QD for 12 weeks.

Subject analysis set title

Cohort 1

Subject analysis set type

Intention-to-treat

Subject analysis set description

Cohort 1 (Subjects without Cirrhosis) received single dose of AL-335 400 milligrams (mg) tablets once daily (QD), odalasvir (ODV) 50 mg tablet and simeprevir 100 mg tablet QD for 8 weeks.

Subject analysis set title

Cohort 1b + Cohort 4

Subject analysis set type

Intention-to-treat

Subject analysis set description

Cohort 1b (Subjects without Cirrhosis) received single dose of AL- 335 800 mg tablets QD and ODV 50 mg tablets every other day (QOD) for 8 weeks; Cohort 4 (Participants without Cirrhosis) received single dose of AL- 335 800 mg tablets QD and ODV 50 mg tablets QOD for 8 weeks.

Subject analysis set title

Cohort 2 + Cohort 3 + Cohort 5

Subject analysis set type

Intention-to-treat

Subject analysis set description

Cohort 2+3+5 (Subjects with Cirrhosis) received single dose of AL-335 800 mg QD, ODV 50 mg QOD and SMV 75 mg QD.

Subject analysis set title

Cohort 6

Subject analysis set type

Intention-to-treat

Subject analysis set description

Cohort 6 (Subjects with Cirrhosis) received single dose of AL-335 800 mg QD, ODV 50 mg QOD and SMV 75 mg QD for 8 weeks.

Subject analysis set title

Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11

Subject analysis set type

Intention-to-treat

Subject analysis set description

Cohort 7+8 +9+11 (Subjects with Cirrhosis) received single dose of AL-335 800 mg QD, ODV 25 mg QD and SMV 75 mg QD.

Primary: Number of Subjects with Treatment-Emergent Adverse Event (TEAE)

Top of page

End point title

Number of Subjects with Treatment-Emergent Adverse Event (TEAE) ^[1]

End point description

An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to the possibility of a causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between administration of study drug and up to 43 weeks that were absent before treatment or that worsened relative to pre-treatment state. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Primary

End point timeframe

Approximately 2.6 years

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Subjects	17	19	14	13	7	4	13	17	10	4

No statistical analyses for this end point

Primary: Body Weight at End of Treatment

Top of page

End point title

Body Weight at End of Treatment ^[2]

End point description

Body weight (measured using a calibrated scale) at end of treatment was reported. Safety set included all subjects enrolled into the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not. Here, N (number of subjects analyzed) signifies number of subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	19	25	20	20	8	5	14	30	15	4
Units: Kilograms (kg)
arithmetic mean (standard deviation)	76.02 ( 15.13 )	84.58 ( 15.09 )	80.19 ( 17.79 )	74.07 ( 12.78 )	73.09 ( 8.62 )	81.30 ( 13.82 )	81.83 ( 13.67 )	80.15 ( 17.92 )	86.02 ( 15.56 )	69.90 ( 11.55 )

No statistical analyses for this end point

Primary: Body Mass Index (BMI) at End of Treatment

Top of page

End point title

Body Mass Index (BMI) at End of Treatment ^[3]

End point description

BMI was calculated by dividing the body weight (in kilogram) by the square of height (in meters). BMI at the end of treatment was reported. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not. Here, N (number of subjects analyzed) signifies number of subjects evaluable for this endpoint.

End point type

Primary

End point timeframe

End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	19	25	20	20	8	5	14	30	15	4
Units: Kilograms per square meter (Kg/m^2)
arithmetic mean (standard deviation)	25.89 ( 4.63 )	28.43 ( 4.26 )	26.45 ( 5.53 )	25.46 ( 3.53 )	25.60 ( 3.21 )	25.60 ( 2.82 )	26.17 ( 4.20 )	27.69 ( 5.28 )	27.98 ( 4.37 )	23.64 ( 4.50 )

No statistical analyses for this end point

Primary: Percentage of Subjects with Worst Post-Baseline Values of Vital Signs

Top of page

End point title

Percentage of Subjects with Worst Post-Baseline Values of Vital Signs ^[4]

End point description

Percentage of subjects with the worst post-baseline values of vital signs (Systolic blood pressure [sBP], Diastolic blood pressure [dBP], and Heart rate) were reported. For sBP, abnormally low: less than or equal to [<=] 90 millimeters mercury [mmHg]; Grade 1 or mild: greater than [>] 140 to less than [<] 160 mmHg; Grade 2 or moderate: >=160 to <180 and Grade 3 or severe: >=180 mmHg. For dBP, abnormally low: <=50 mmHg; Grade 1 or mild: >90 to <100 mmHg; Grade 2 or moderate: >=100 to <110 mmHg and Grade 3 or severe: >=110 mmHg. For Heart Rate, abnormally low: <=50 beats per minute [bpm] and abnormally high: >=120 bpm) were reported. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Primary

End point timeframe

Up to 43 weeks

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subjects
number (not applicable)
sBP: Abnormally low	0	0	0	0	0	0	0	3.3	0	0
sBP: Grade 1 or mild	20.0	32.0	35.0	25.0	37.5	60.0	57.1	26.7	46.7	25.0
sBP: Grade 2 or moderate	10.0	8.0	0	5.0	37.5	0	7.1	20.0	13.3	50.0
sBP: Grade 3 or severe	0	4.0	5.0	0	0	0	0	3.3	13.3	0
dBP: Abnormally low	0	4.0	0	0	12.5	0	0	0	0	0
dBP: Grade 1 or mild	5.0	20.0	35.0	20.0	0	60.0	21.4	10.0	26.7	0
dBP: Grade 2 or moderate	5.0	12.0	0	0	0	0	14.3	13.3	6.7	25.0
dBP: Grade 3 or severe	0	0	0	0	25.0	0	7.1	3.3	6.7	0
Heart Rate: Abnormally low	35.0	32.0	35.0	30.0	50.0	20.0	21.4	13.3	13.3	0
Heart Rate: Abnormally high	0	0	0	0	12.5	0	0	0	0	0

No statistical analyses for this end point

Primary: Percentage of Subjects with Maximum Decrease from Baseline in Mean Ejection Fraction

Top of page

End point title

Percentage of Subjects with Maximum Decrease from Baseline in Mean Ejection Fraction ^[5]

End point description

Percentage of subjects with maximum decrease from baseline in mean ejection fraction was reported. Percentages are based on the number of subjects with available data. Safety set included all subjects enrolled into the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Primary

End point timeframe

Baseline up to End of treatment (up to 43 weeks)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subjects
number (not applicable)
Decline of > 10%	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Decline of >5-<=10%	0.0	4.0	10.0	10.0	12.5	0.0	21.4	3.3	6.7	0.0
Decline of >0-<=5%	65.0	48.0	60.0	50.0	50.0	20.0	64.3	80.0	46.7	50.0

No statistical analyses for this end point

Primary: Percentage of Subjects by Treatment-Emergent Toxicity Grade - Hematology Parameters

Top of page

End point title

Percentage of Subjects by Treatment-Emergent Toxicity Grade - Hematology Parameters ^[6]

End point description

Percentage of subjects by treatment-emergent toxicity grade (1, 2, 3, 4 and 3+4) for Hematology parameters (hemoglobin, lymphocytes, neutrophils, leukocytes, platelets) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. Toxicity is treatment-emergent if it is worse than the baseline or if the baseline is missing. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Primary

End point timeframe

Up to 43 weeks

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subjects
number (not applicable)
Hemoglobin: Grade 1	5.0	0.0	0.0	5.0	0.0	0.0	0.0	0.0	0.0	0.0
Hemoglobin: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Hemoglobin: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Hemoglobin: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Hemoglobin: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Lymphocytes: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	6.7	0.0	0.0
Lymphocytes: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	7.1	10.0	0.0	0.0
Lymphocytes: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Lymphocytes: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Lymphocytes: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Neutrophils: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Neutrophils: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Neutrophils: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Neutrophils: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Neutrophils: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Leukocytes: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	10.0	0.0	0.0
Leukocytes: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Leukocytes: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Leukocytes: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Leukocytes: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Platelets: Grade 1	5.0	0.0	5.0	5.0	0.0	0.0	7.1	6.7	13.3	25.0
Platelets: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	16.7	0.0	0.0
Platelets: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Platelets: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Platelets: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

No statistical analyses for this end point

Primary: Percentage of Subjects by Treatment-Emergent Toxicity Grade - Blood Chemistry Parameters

Top of page

End point title

Percentage of Subjects by Treatment-Emergent Toxicity Grade - Blood Chemistry Parameters ^[7]

End point description

Percentage of subjects by treatment-emergent toxicity grade (Grade 1,2,3,4,3+4) for Blood Chemistry (Calcium, Phosphate, Potassium, Sodium, Bicarbonate, Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Direct Bilirubin, Glucose, Cholesterol, Triglycerides, Urate, Triacylglycerol lipase, Creatinine, Creatinine clearance, Albumin, and Creatine kinase) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. Toxicity is treatment-emergent if it is worse than the baseline or if the baseline is missing. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Primary

End point timeframe

Up to 43 weeks

Notes
[7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subjects
number (not applicable)
Calcium: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	3.3	13.3	0.0	0.0
Calcium: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Calcium: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Calcium: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Calcium: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Phosphate: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Phosphate: Grade 2	10.0	20.0	25.0	15.0	12.5	0.0	14.3	13.3	6.7	0.0
Phosphate: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	21.4	3.3	0.0	0.0
Phosphate: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Phosphate: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	21.4	3.3	0.0	0.0
Potassium: Grade 1	0.0	4.0	0.0	0.0	0.0	0.0	0.0	6.7	0.0	0.0
Potassium: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Potassium: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Potassium: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Potassium: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Sodium: Grade 1	0.0	8.0	5.0	0.0	12.5	20.0	0.0	3.3	20.0	0.0
Sodium: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Sodium: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Sodium: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Sodium: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Bicarbonate: Grade 1	0.0	16.0	15.0	5.0	12.5	20.0	7.1	0.0	0.0	0.0
Bicarbonate: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	6.7	0.0	0.0
Bicarbonate: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Bicarbonate: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Bicarbonate: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Alanine aminotransferase: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	0.0	0.0
Alanine aminotransferase: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Alanine aminotransferase: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Alanine aminotransferase: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	6.7	0.0	0.0
Alanine aminotransferase: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	6.7	0.0	0.0
Alkaline phosphatase: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	6.7	0.0	0.0
Alkaline phosphatase: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Alkaline phosphatase: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Alkaline phosphatase: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Alkaline phosphatase: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Aspartate aminotransferase: Grade: 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	25.0
Aspartate aminotransferase: Grade: 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	0.0	0.0
Aspartate aminotransferase: Grade: 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	6.7	0.0
Aspartate aminotransferase: Grade: 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Aspartate aminotransferase: Grade: 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	6.7	0.0
Bilirubin: Grade 1	0.0	0.0	10.0	10.0	0.0	0.0	0.0	3.3	0.0	0.0
Bilirubin: Grade 2	5.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	0.0	25.0
Bilirubin: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	0.0	0.0
Bilirubin: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Bilirubin: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	0.0	0.0
Direct bilirubin: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Direct bilirubin: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Direct bilirubin: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	6.7	0.0
Direct bilirubin: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Direct bilirubin: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	6.7	0.0
Glucose: Grade 1	15.0	4.0	10.0	5.0	25.0	0.0	35.7	10.0	13.3	0.0
Glucose: Grade 2	0.0	4.0	5.0	0.0	12.5	0.0	14.3	13.3	13.3	25.0
Glucose: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	0.0	0.0
Glucose: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Glucose: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	0.0	0.0
Cholesterol: Grade 1	20.0	24.0	30.0	35.0	12.5	0.0	42.9	3.3	20.0	50.0
Cholesterol: Grade 2	15.0	8.0	5.0	5.0	37.5	0.0	0.0	6.7	6.7	0.0
Cholesterol: Grade 3	0.0	0.0	5.0	0.0	0.0	0.0	0.0	3.3	0.0	0.0
Cholesterol: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Cholesterol: Grade 3+4	0.0	0.0	5.0	0.0	0.0	0.0	0.0	3.3	0.0	0.0
Triglycerides: Grade 1	5.0	16.0	10.0	15.0	50.0	20.0	28.6	16.7	33.3	25.0
Triglycerides: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	14.3	0.0	0.0	0.0
Triglycerides: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Triglycerides: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Triglycerides: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Urate: Grade 1	5.0	12.0	5.0	0.0	12.5	0.0	28.6	10.0	26.7	0.0
Urate: Grade 2	0.0	4.0	0.0	5.0	0.0	0.0	0.0	3.3	0.0	0.0
Urate: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Urate: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Urate: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Triacylglycerol lipase: Grade 1	5.0	12.0	5.0	0.0	12.5	20.0	7.1	13.3	0.0	0.0
Triacylglycerol lipase: Grade 2	15.0	4.0	10.0	0.0	12.5	0.0	7.1	3.3	0.0	0.0
Triacylglycerol lipase: Grade 3	5.0	8.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Triacylglycerol lipase: Grade 4	0.0	0.0	5.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Triacylglycerol lipase: Grade 3+4	5.0	8.0	5.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatinine: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatinine: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	7.1	0.0	0.0	0.0
Creatinine: Grade 3	0.0	0.0	0.0	0.0	12.5	0.0	0.0	3.3	0.0	0.0
Creatinine: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatinine: Grade 3+4	0.0	0.0	0.0	0.0	12.5	0.0	0.0	3.3	0.0	0.0
Creatinine clearance: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatinine clearance: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatinine clearance: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatinine clearance: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatinine clearance: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Albumin: Grade 1	5.0	4.0	0.0	0.0	25.0	0.0	0.0	0.0	0.0	0.0
Albumin: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Albumin: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Albumin: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Albumin: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatine kinase: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	7.1	0.0	0.0	0.0
Creatine kinase: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	6.7	0.0
Creatine kinase: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatine kinase: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Creatine kinase: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

No statistical analyses for this end point

Primary: Percentage of Subjects by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)

Top of page

End point title

Percentage of Subjects by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR) ^[8]

End point description

Percentage of subjects by treatment-emergent toxicity grade for coagulation parameter (Prothrombin International Normalized Ratio) were reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. Toxicity is treatment-emergent if it is worse than the baseline or if the baseline is missing. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Primary

End point timeframe

Up to 43 weeks

Notes
[8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subject
number (not applicable)
Prothrombin INR: Grade 1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Prothrombin INR: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Prothrombin INR: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Prothrombin INR: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Prothrombin INR: Grade 3+4	0.0	4.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0

No statistical analyses for this end point

Primary: Percentage of Subject by Treatment-Emergent Toxicity Grade - Urinalysis Parameter - Protien

Top of page

End point title

Percentage of Subject by Treatment-Emergent Toxicity Grade - Urinalysis Parameter - Protien ^[9]

End point description

Percentage of subjects by treatment-emergent toxicity grade (Grade 1, 2, 3, 4, 3+4) for urinalysis parameter (protein) was reported. Toxicity grades were defined as Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe and Grade 4: potentially life-threatening. Toxicity is treatment-emergent if it is worse than the baseline or if the baseline is missing. Safety set included all subject enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Primary

End point timeframe

Up to 43 weeks

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subject
number (not applicable)
Protein: Grade 1	0.0	4.0	0.0	0.0	0.0	0.0	7.1	3.3	26.7	50.0
Protein: Grade 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	13.3	0.0
Protein: Grade 3	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	0.0	25.0
Protein: Grade 4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Protein: Grade 3+4	0.0	0.0	0.0	0.0	0.0	0.0	0.0	3.3	0.0	25.0

No statistical analyses for this end point

Primary: Percentage of Subjects with Worst Treatment-Emergent Abnormalities of Electrocardiogram (ECG) Parameters

Top of page

End point title

Percentage of Subjects with Worst Treatment-Emergent Abnormalities of Electrocardiogram (ECG) Parameters ^[10]

End point description

Percentage of subjects with worst treatment-emergent abnormalities of ECG parameters (Fridericia Corrected QT interval [QTcF], Bazett Corrected QT interval [QTcB], Heart rate, QRS and PR, was reported. For QTcF abnormality was defined as 30 milliseconds (ms) less than or equal to (<=) QTcF increase from baseline <= 60 ms; for QTcB abnormality was defined as 30 ms <= QTcB increase from baseline <= 60 ms; for heart rate - abnormal low: <= 50 beats per minute (bpm) and abnormal high: >= 120 bpm; for QRS – abnormal high: >120 ms; for PR - abnormally low: PR < 120 ms; abnormally high - 200 ms < PR <= 240 ms and 240 ms < PR <= 300 ms. Safety set included all subjects enrolled into the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Primary

End point timeframe

Up to 43 weeks

Notes
[10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were done, no inferential statistical analyses were performed.

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subject
number (not applicable)
QTcF: Abnormal	5.0	0.0	5.0	0.0	0.0	0.0	7.1	3.3	0.0	0.0
QTcB: Abnormal	5.0	8.0	10.0	0.0	0.0	0.0	28.6	3.3	6.7	0.0
Heart rate: Abnormal low	25.0	16.0	10.0	15.0	25.0	20.0	14.3	13.3	0.0	25.0
Heart rate: Abnormal high	0.0	0.0	0.0	0.0	12.5	0.0	0.0	0.0	0.0	0.0
QRS: Abnormal high	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
PR: Abnormally low (PR<120 ms)	0.0	0.0	0.0	0.0	0.0	0.0	7.1	3.3	0.0	0.0
PR: Abnormally high (200 ms<PR<= 240 ms)	5.0	8.0	15.0	10.0	0.0	0.0	0.0	6.7	13.3	0.0
PR: Abnormal high (240 ms<PR<=300 ms)	10.0	0.0	0.0	0.0	0.0	0.0	7.1	0.0	0.0	0.0

No statistical analyses for this end point

Secondary: Percentage of Subjects with Sustained Virologic Response (SVR) at week 4, 12 and 24 After end of Treatment

Top of page

End point title

Percentage of Subjects with Sustained Virologic Response (SVR) at week 4, 12 and 24 After end of Treatment

End point description

Subjects were considered to have achieved SVR if the Hepatitis C virus (HCV) Ribonucleic acid (RNA) less than (<) Lower limit of quantification (LLOQ) (<15 international unit per milliliter [IU/mL]) detectable or undetectable at Week 4, 12 and 24 after the actual end of study drug treatment. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not. Here ‘99999’ indicates that the upper and lower limit of CI was not estimable as no subject achieved SVR at specified timepoint.

End point type

Secondary

End point timeframe

At Week 4, 12 and Week 24 after end of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of Subjects
number (confidence interval 95%)
4 weeks after end of treatment	100 (83.2 to 100)	96.0 (79.6 to 99.9)	100 (83.2 to 100)	100 (83.2 to 100)	87.5 (47.3 to 99.7)	0 (-99999 to 99999)	71.4 (41.9 to 91.6)	100 (88.4 to 100)	93.3 (68.1 to 99.8)	100 (39.8 to 100)
12 weeks after end of treatment	100 (83.2 to 100)	84.0 (63.9 to 95.5)	100 (83.2 to 100)	100 (83.2 to 100)	87.5 (47.3 to 99.7)	0 (-99999 to 99999)	71.4 (41.9 to 91.6)	96.7 (82.8 to 99.9)	93.3 (68.1 to 99.8)	100 (39.8 to 100)
24 weeks after end of treatment	100 (83.2 to 100)	84.0 (63.9 to 95.5)	100 (83.2 to 100)	100 (83.2 to 100)	87.5 (47.3 to 99.7)	0 (-99999 to 99999)	71.4 (41.9 to 91.6)	96.7 (82.3 to 99.9)	93.3 (68.1 to 99.8)	100 (39.8 to 100)

No statistical analyses for this end point

Secondary: Minimum Observed Plasma Concentration (Cmin) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

Top of page

End point title

Minimum Observed Plasma Concentration (Cmin) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

End point description

Cmin is the minimum observed plasma concentration of AL-335 and its metabolites (ALS-022399, and ALS-022227). For Pharmacokinetic (PK) analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: nanogram per milliliter (ng/ml)
arithmetic mean (standard deviation)
AL-335	0.0 ( 0.0 )	0.0 ( 0.0 )	0.0 ( 0.0 )	0.0 ( 0.0 )	0.0 ( 0.0 )
ALS-022399	0.000 ( 0.000 )	0.000 ( 0.000 )	0.308 ( 1.233 )	0.000 ( 0.000 )	0.280 ( 0.814 )
ALS-022227	35.73 ( 13.61 )	35.80 ( 11.15 )	57.25 ( 31.63 )	68.30 ( 38.33 )	64.96 ( 28.63 )

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolite (ALS-022399 and ALS-022227)

Top of page

End point title

Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolite (ALS-022399 and ALS-022227)

End point description

Cmax is the maximum observed plasma concentration of AL-335 and its metabolite (ALS-022227). For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng/mL
arithmetic mean (standard deviation)
AL-335	414.79 ( 317.93 )	547.36 ( 226.06 )	563.04 ( 423.53 )	529.17 ( 265.17 )	677.59 ( 554.83 )
ALS-022399	103.57 ( 52.25 )	148.89 ( 48.77 )	174.89 ( 87.05 )	158.80 ( 55.97 )	186.28 ( 113.18 )
ALS-022227	364.4 ( 129.1 )	392.6 ( 144.2 )	658.0 ( 275.1 )	643.2 ( 318.4 )	619.7 ( 224.1 )

No statistical analyses for this end point

Secondary: Trough Plasma Concentration (Ctrough) for AL-335 and its metabolites (ALS-022399 and ALS-022227)

Top of page

End point title

Trough Plasma Concentration (Ctrough) for AL-335 and its metabolites (ALS-022399 and ALS-022227)

End point description

Ctrough is the trough plasma concentration for AL-335, ALS-022399, and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set participants except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis. Here '99999' indicates that the data was not evaluated as there were no subjects analyzed at specified timepoint. Here 'n' signifies the number of subjects analyzed at this time point.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)
AL-335 (n=0, 0, 0, 0)	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )
ALS-022399 (n=0, 0, 6, 2, 8)	99999 ( 99999 )	99999 ( 99999 )	4.640 ( 4.018 )	4.570 ( 2.899 )	4.400 ( 2.560 )
ALS-022227 (n=11, 11, 6, 27)	42.74 ( 19.26 )	36.77 ( 10.42 )	61.82 ( 35.47 )	86.20 ( 56.31 )	73.85 ( 35.15 )

No statistical analyses for this end point

Secondary: Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

Top of page

End point title

Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

End point description

Tmax is the time to reach the maximum plasma concentration of AL-335, ALS-022399, and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: Hours
median (full range (min-max))
AL-335	2.000 (0.50 to 4.00)	2.000 (1.00 to 4.00)	1.500 (1.00 to 4.00)	1.000 (1.00 to 2.00)	2.000 (0.50 to 4.00)
ALS-022399	4.000 (1.00 to 6.00)	3.000 (2.00 to 4.00)	3.000 (1.00 to 4.00)	2.000 (1.00 to 4.00)	3.000 (2.00 to 6.00)
ALS-022227	4.000 (2.00 to 4.60)	4.000 (3.00 to 6.00)	3.500 (2.00 to 6.00)	3.500 (2.00 to 6.00)	4.000 (2.00 to 6.00)

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

Top of page

End point title

Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

End point description

AUC(0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of AL-335 and its metabolites (ALS-022399, and ALS-022227). For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: nanogramhours per milliliters (ngh/mL)
arithmetic mean (standard deviation)
AL-335	1049.3 ( 890.0 )	1185.8 ( 502.8 )	1526.3 ( 1328.9 )	1178.5 ( 594.0 )	1774.8 ( 1348.5 )
ALS-022399	469.3 ( 224.0 )	660.7 ( 211.5 )	945.2 ( 551.1 )	844.2 ( 287.9 )	933.3 ( 544.3 )
ALS-022227	2920.0 ( 1029.1 )	3238.2 ( 972.8 )	5258.1 ( 1969.4 )	5218.3 ( 2011.9 )	5425.2 ( 1878.2 )

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration Time-Curve at 24 hours (AUC0-24) for AL-335 and its Metabolites (ALS-022399 and ALS-022227)

Top of page

End point title

Area Under the Plasma Concentration Time-Curve at 24 hours (AUC0-24) for AL-335 and its Metabolites (ALS-022399 and ALS-022227)

End point description

AUC(0-24) is the area under the plasma concentration-time curve from time zero to time 24 hours for AL-335, ALS-022399, and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng*h/mL
arithmetic mean (standard deviation)
AL-335	1058.0 ( 886.9 )	1197.2 ( 507.7 )	1532.7 ( 1329.5 )	1187.3 ( 600.9 )	1792.2 ( 1350.9 )
ALS-022399	500.5 ( 230.8 )	718.0 ( 240.7 )	1009.7 ( 599.4 )	932.7 ( 330.1 )	1044.7 ( 561.1 )
ALS-022227	2897.0 ( 1081.8 )	3238.2 ( 972.8 )	5258.1 ( 1969.4 )	4806.0 ( 1945.4 )	5425.2 ( 1878.2 )

No statistical analyses for this end point

Secondary: Last Measurable Plasma Concentration (Clast) of AL-335 and its Metabolite (ALS-022399 and ALS-022227)

Top of page

End point title

Last Measurable Plasma Concentration (Clast) of AL-335 and its Metabolite (ALS-022399 and ALS-022227)

End point description

Clast is the last measurable plasma concentration (Clast) of AL-335, ALS-022399, and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)
AL-335	5.931 ( 4.752 )	7.077 ( 4.676 )	4.983 ( 3.339 )	5.698 ( 5.620 )	5.811 ( 8.622 )
ALS-022399	5.995 ( 1.649 )	10.335 ( 5.558 )	14.591 ( 10.741 )	14.793 ( 8.738 )	17.520 ( 10.972 )
ALS-022227	38.28 ( 12.20 )	47.26 ( 10.68 )	67.08 ( 40.66 )	69.18 ( 38.01 )	72.14 ( 29.23 )

No statistical analyses for this end point

Secondary: Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and its Metabolites (ALS-022399 and ALS-022227)

Top of page

End point title

Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and its Metabolites (ALS-022399 and ALS-022227)

End point description

Tlast is the time corresponding to last measurable plasma concentration for AL-335, ALS-022399 and ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: Hours
median (full range (min-max))
AL-335	6.000 (6.00 to 9.00)	6.000 (6.00 to 9.00)	6.000 (4.00 to 24.10)	6.025 (1.01 to 9.00)	8.670 (5.98 to 12.00)
ALS-022399	12.000 (9.00 to 12.00)	12.000 (12.00 to 12.00)	12.000 (9.00 to 24.10)	12.000 (12.00 to 12.00)	12.000 (8.50 to 24.00)
ALS-022227	24.00 (24.0 to 24.1)	24.00 (23.7 to 24.1)	24.00 (24.0 to 24.1)	24.00 (24.0 to 24.2)	23.90 (23.5 to 24.0)

No statistical analyses for this end point

Secondary: Average Plasma Concentration at Steady State (Css.avg) of ALS-022227

Top of page

End point title

Average Plasma Concentration at Steady State (Css.avg) of ALS-022227

End point description

Css.avg is the average plasma concentration at the steady state of ALS-022227. For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	121.49 ( 42.81 )	135.20 ( 41.16 )	218.88 ( 81.80 )	217.17 ( 83.26 )	227.37 ( 78.46 )

No statistical analyses for this end point

Secondary: Cmin of Simeprevir

Top of page

End point title

Cmin of Simeprevir

End point description

Cmin is the minimum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	379.75 ( 247.02 )	452.65 ( 641.99 )	517.00 ( 416.45 )	561.19 ( 424.71 )

No statistical analyses for this end point

Secondary: Cmax of Simeprevir

Top of page

End point title

Cmax of Simeprevir

End point description

Cmax is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	1927.7 ( 1205.3 )	1537.6 ( 1325.2 )	1769.3 ( 881.6 )	1925.1 ( 1034.0 )

No statistical analyses for this end point

Secondary: Ctrough of Simeprevir

Top of page

End point title

Ctrough of Simeprevir

End point description

Ctrough is the trough plasma concentration of Simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	475.42 ( 317.63 )	570.64 ( 816.36 )	669.00 ( 442.50 )	636.88 ( 455.94 )

No statistical analyses for this end point

Secondary: Tmax of Simeprevir

Top of page

End point title

Tmax of Simeprevir

End point description

Tmax is the Time to reach the maximum plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	16	6	27
Units: Hours
median (full range (min-max))	6.000 (4.00 to 12.00)	6.000 (4.00 to 9.00)	6.000 (4.00 to 6.05)	6.000 (3.00 to 8.50)

No statistical analyses for this end point

Secondary: AUC (0-last) of Simeprevir

Top of page

End point title

AUC (0-last) of Simeprevir

End point description

AUC (0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not the duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	16	6	27
Units: ng*h/ml
arithmetic mean (standard deviation)	25018.2 ( 15248.7 )	23061.3 ( 24724.4 )	25266.7 ( 15523.4 )	27070.7 ( 15895.7 )

No statistical analyses for this end point

Secondary: AUC (0-24) of Simeprevir

Top of page

End point title

AUC (0-24) of Simeprevir

End point description

AUC (0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

End point values	Cohort 1	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	16	6	27
Units: ng*h/ml
arithmetic mean (standard deviation)	25018.2 ( 15248.7 )	23061.3 ( 24724.4 )	25266.7 ( 15523.4 )	27070.7 ( 15895.7 )

No statistical analyses for this end point

Secondary: Clast of Simeprevir

Top of page

End point title

Clast of Simeprevir

End point description

Clast is the maximum measured plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	402.55 ( 244.20 )	481.76 ( 644.76 )	538.67 ( 456.21 )	602.60 ( 453.12 )

No statistical analyses for this end point

Secondary: Tlast of Simeprevir

Top of page

End point title

Tlast of Simeprevir

End point description

Tlast is the time corresponding to last measurable plasma concentration of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	16	6	27
Units: ng/ml
median (full range (min-max))	24.00 (24.0 to 24.1)	24.00 (24.0 to 24.1)	24.00 (24.0 to 24.2)	23.90 (23.5 to 24.0)

No statistical analyses for this end point

Secondary: Average Plasma Concentration at Steady State (Css,avg) of Simeprevir

Top of page

End point title

Average Plasma Concentration at Steady State (Css,avg) of Simeprevir

End point description

Css,avg is the average plasma concentration at steady state of simeprevir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	1042.8 ( 0.03 )	960.5 ( 1030.7 )	1053.8 ( 1053.8 )	1134.6 ( 666.6 )

No statistical analyses for this end point

Secondary: Cmin of Odalasvir

Top of page

End point title

Cmin of Odalasvir

End point description

Cmin is the minimum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	322.45 ( 139.21 )	97.21 ( 58.62 )	107.90 ( 49.46 )	102.73 ( 47.08 )	131.31 ( 62.31 )

No statistical analyses for this end point

Secondary: Cmax of Odalasvir

Top of page

End point title

Cmax of Odalasvir

End point description

Cmin is the maximum observed plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	634.27 ( 257.29 )	363.36 ( 184.48 )	322.46 ( 167.29 )	232.85 ( 187.53 )	298.67 ( 133.99 )

No statistical analyses for this end point

Secondary: Ctrough of Odalasvir

Top of page

End point title

Ctrough of Odalasvir

End point description

Ctrough is the trough plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	335.18 ( 146.14 )	100.98 ( 61.90 )	112.44 ( 51.53 )	119.82 ( 58.87 )	141.56 ( 64.81 )

No statistical analyses for this end point

Secondary: Tmax of Odalasvir

Top of page

End point title

Tmax of Odalasvir

End point description

Tmax is the time to reach the maximum plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: Hours
median (full range (min-max))	6.000 (4.00 to 12.00)	6.000 (4.00 to 12.00)	6.000 (3.00 to 9.00)	4.500 (0.00 to 9.00)	6.000 (3.98 to 9.00)

No statistical analyses for this end point

Secondary: AUC (0-last) of Odalasvir

Top of page

End point title

AUC (0-last) of Odalasvir

End point description

AUC(0-last) is the area under the plasma concentration-time curve from time 0 to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng*h/ml
arithmetic mean (standard deviation)	11805.5 ( 4902.6 )	8635.5 ( 4656.7 )	8648.1 ( 4161.1 )	7050.0 ( 4001.4 )	8422.2 ( 3617.8 )

No statistical analyses for this end point

Secondary: AUC (0-24) for Odalasvir

Top of page

End point title

AUC (0-24) for Odalasvir

End point description

AUC(0-24) is the area under the plasma concentration-time curve from time zero to time 24 hours for odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng*h/mL
arithmetic mean (standard deviation)	11805.5 ( 4902.6 )	5530.0 ( 2930.3 )	5393.8 ( 2695.4 )	4048.3 ( 2727.8 )	4924.1 ( 2122.9 )

No statistical analyses for this end point

Secondary: Clast of Odalasvir

Top of page

End point title

Clast of Odalasvir

End point description

Clast is the last measurable plasma concentration (Clast) of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	384.09 ( 172.29 )	162.65 ( 87.39 )	163.54 ( 78.10 )	131.92 ( 74.01 )	152.47 ( 66.50 )

No statistical analyses for this end point

Secondary: Tlast of Odalasvir

Top of page

End point title

Tlast of Odalasvir

End point description

Tlast is the time corresponding to last measurable plasma concentration of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: Hours
median (full range (min-max))	24.00 (24.0 to 24.1)	47.60 (47.5 to 47.7)	47.50 (47.4 to 47.9)	47.80 (47.4 to 48.0)	47.50 (47.5 to 47.9)

No statistical analyses for this end point

Secondary: Average Plasma Concentration at Steady State (Css,avg) of Odalasvir

Top of page

End point title

Average Plasma Concentration at Steady State (Css,avg) of Odalasvir

End point description

Css,avg is average plasma concentration at steady state of odalasvir. For PK analyses, cohorts were grouped by treatment dosage (not duration of treatment) for subjects without cirrhosis (Cohort 1; Cohort 1b+4; Cohort 2+3+5) and for subjects with cirrhosis (Cohort 6; Cohort 7+8+9+11). PK set: all safety set subjects except those who violated inclusion/exclusion criteria, deviated from protocol, or if data were unavailable/incomplete which influenced PK analysis.

End point type

Secondary

End point timeframe

Predose, 0.5, 1, 2, 3, 4, 6, 9, and 24 hours postdose (Week 2), 2-4 hours postdose (Weeks 3 and 6), 6-8 hours postdose (Weeks 4 and 8)

End point values	Cohort 1	Cohort 1b + Cohort 4	Cohort 2 + Cohort 3 + Cohort 5	Cohort 6	Cohort 7 + Cohort 8 + Cohort 9 + Cohort 11
Number of subjects analysed	11	11	16	6	27
Units: ng/ml
arithmetic mean (standard deviation)	491.55 ( 203.85 )	181.60 ( 97.99 )	181.58 ( 87.25 )	147.40 ( 83.86 )	176.86 ( 75.91 )

No statistical analyses for this end point

Secondary: Percentage of Subjects with Virologic Relapse During the Follow-up Period

Top of page

End point title

Percentage of Subjects with Virologic Relapse During the Follow-up Period

End point description

Viral relapse is defined as subjects SVR12, with HCV RNA <LLOQ at the actual end of study drug treatment and confirmed HCV RNA greater than or equal to (>=) LLOQ during follow up. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Secondary

End point timeframe

Follow up period (Up to Week 12 after end of treatment)

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subjects
number (not applicable)	0	16.0	0	0	0	100.0	14.3	3.3	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects with On-treatment Failure

Top of page

End point title

Percentage of Subjects with On-treatment Failure

End point description

On-treatment failure was defined by subjects who did not achieve SVR12 and with confirmed HCV RNA >= LLOQ at the actual end of study drug treatment. Safety set included all subjects enrolled into the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Secondary

End point timeframe

Up to 12 weeks

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subjects
number (not applicable)	0	0	0	0	12.5	0	7.1	0	0	0

No statistical analyses for this end point

Secondary: Percentage of Subjects who Acheived HCV RNA less then (<) LLOQ Undetectable

Top of page

End point title

Percentage of Subjects who Acheived HCV RNA less then (<) LLOQ Undetectable

End point description

Percentage of subjects who acheived HCV RNA less then (<) LLOQ undetectable was reported. Safety set included all subjects enrolled into the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not. Here '99999' indicates that the data was not evaluated as subjects ended the treatment at the specified timepoint.

End point type

Secondary

End point timeframe

Day 2, 3, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and End of treatment (Cohort 3: 6 weeks; Cohort 1, Cohort 1b+ Cohort 4, Cohort 2, Cohort 5a, and Cohort 6, 7, 8: 8 weeks; Cohort 4, Cohort 5b, Cohort 9 and Cohort 11: 12 weeks)

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subjects
number (not applicable)
Day 2	0	0	0	0	0	0	0	0	0	0
Day 3	0	0	0	5.0	0	0	0	0	6.7	0
Week 1	5.0	20.0	0	30.0	12.5	20.0	35.7	16.7	13.3	25.0
Week 2	35.0	44.0	45.0	70.0	25.0	40.0	64.3	50.0	66.7	75.0
Week 3	70.0	76.0	75.0	80.0	62.5	60.0	85.7	73.3	86.7	100
Week 4	80.0	92.0	90.0	85.0	87.5	60.0	92.9	80.0	86.7	100
Week 5	100	96.0	100	90.0	100	80.0	92.9	90.0	100	100
Week 6	90.0	100	85.0	90.0	100	100	92.9	96.7	100	100
Week 7	90.0	96.0	95.0	99999	100	80.0	85.7	100	100	100
Week 8	95.0	100	100	99999	87.5	100	85.7	100	93.3	100
Week 9	99999	99999	99999	99999	87.5	99999	92.9	99999	93.3	100
Week 10	99999	99999	99999	99999	87.5	99999	92.9	99999	93.3	100
Week 11	99999	99999	99999	99999	87.5	99999	92.9	99999	86.7	100
Week 12	99999	99999	99999	99999	100	99999	85.7	99999	93.3	100
End of treatment	95.0	100	100	90.0	87.5	100	85.7	100	93.3	100

No statistical analyses for this end point

Secondary: Percentage of Subjects who Achieved HCV RNA <LLOQ

Top of page

End point title

Percentage of Subjects who Achieved HCV RNA <LLOQ

End point description

Percentage of subjects who achieved HCV RNA <LLOQ was reported. Safety set included all subjects enrolled into the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not. Here '99999' indicates that the data was not evaluated as subjects ended the treatment at the specified timepoint.

End point type

Secondary

End point timeframe

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	20	25	20	20	8	5	14	30	15	4
Units: Percentage of subjects
number (not applicable)
Day 2	0	0	0	0	0	0	0	0	0	0
Day 3	0	0	0	0	0	0	0	0	0	0
Week 1	0	8.0	0	10.0	0	0	14.3	16.7	13.3	25.0
Week 2	20.0	20.0	15.0	40.0	0	20.0	42.9	50.0	66.7	75.0
Week 3	40.0	40.0	45.0	65.0	37.5	60.0	50.0	73.3	86.7	100
Week 4	55.0	52.0	60.0	80.0	62.5	40.0	78.6	80.0	86.7	100
Week 5	75.0	96.0	85.0	85.0	75.0	80.0	85.7	90.0	100	100
Week 6	80.0	88.0	85.0	80.0	87.5	80.0	92.9	96.7	100	100
Week 7	80.0	92.0	95.0	99999	87.5	80.0	85.7	100	100	100
Week 8	85.0	96.0	100	99999	87.5	100	85.7	100	93.3	100
Week 9	99999	99999	99999	99999	87.5	99999	92.9	99999	93.3	100
Week 10	99999	99999	99999	99999	87.5	99999	92.9	99999	93.3	100
Week 11	99999	99999	99999	99999	87.5	99999	92.9	99999	86.7	100
Week 12	99999	99999	99999	99999	87.5	99999	78.6	99999	93.3	100
End of treatment	85.0	96.0	100	80.0	87.5	100	78.6	100	93.3	100

No statistical analyses for this end point

Secondary: Time to Achieve Undetectable HCV RNA or < LLOQ HCV RNA

Top of page

End point title

Time to Achieve Undetectable HCV RNA or < LLOQ HCV RNA

End point description

Time to achieve undetectable HCV RNA or < LLOQ HCV RNA was reported. Safety set included all subjects enrolled into the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

End point type

Secondary

End point timeframe

Up to Week 24 (follow up visit)

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	0 ^[11]	0 ^[12]	0 ^[13]	0 ^[14]	0 ^[15]	0 ^[16]	0 ^[17]	0 ^[18]	0 ^[19]	0 ^[20]
Units: Hours
median (full range (min-max))	( to )	( to )	( to )	( to )	( to )	( to )	( to )	( to )	( to )	( to )

Notes
[11] - The endpoint was not analyzed as per the change in planned analysis
[12] - The endpoint was not analyzed as per the change in planned analysis
[13] - The endpoint was not analyzed as per the change in planned analysis
[14] - The endpoint was not analyzed as per the change in planned analysis
[15] - The endpoint was not analyzed as per the change in planned analysis
[16] - The endpoint was not analyzed as per the change in planned analysis
[17] - The endpoint was not analyzed as per the change in planned analysis
[18] - The endpoint was not analyzed as per the change in planned analysis
[19] - The endpoint was not analyzed as per the change in planned analysis
[20] - The endpoint was not analyzed as per the change in planned analysis

No statistical analyses for this end point

Secondary: Number of Subjects With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Subjects with Virologic Failure

Top of page

End point title

Number of Subjects With HCV Nonstructural Protein NS5A, NS5B, and NS3/4A Sequence in Subjects with Virologic Failure

End point description

Sequencing of the HCV nonstructural protein 3/4A (NS3/4A), nonstructural protein 5A (NS5A) and nonstructural protein 5B (NS5B) genes was done to identify pre-existing sequence polymorphisms and characterize emerging HCV viral variants in subjects with virologic failure. Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not. Subjects who had virologic failure were included in this outcome measure.

End point type

Secondary

End point timeframe

Up to Week 24 (Follow up visit)

End point values	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Number of subjects analysed	0 ^[21]	4	0 ^[22]	0 ^[23]	1	5	3	1	0 ^[24]	0 ^[25]
Units: Subjects
number (not applicable)		4			1	0	2	1

Notes
[21] - No subject had virologic failure.
[22] - No subject had virologic failure.
[23] - No subject had virologic failure.
[24] - No subject had virologic failure.
[25] - No subject had virologic failure.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to 43 weeks

Adverse event reporting additional description

Safety set included all subjects enrolled in the study who had received at least 1 dose of any study drug, whether prematurely withdrawn from the study or not.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

19.1

Reporting group title

Cohort 1 (8 Weeks Genotype [GT1])

Reporting group description

Cohort 1 (Subjects without Cirrhosis) received single dose of AL-335 400 milligrams (mg) tablets once daily (QD), odalasvir (ODV) 50 mg tablet and simeprevir 100 mg tablet QD for 8 weeks.

Reporting group title

Cohort 1b + Cohort 4 (8 Weeks GT1)

Reporting group description

Reporting group title

Cohort 2 (8 Weeks GT1)

Reporting group description

Cohort 2 (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 8 weeks.

Reporting group title

Cohort 3 (Subjects with Cirrhosis)

Reporting group description

Cohort 3 (Subjects with Cirrhosis) received single dose of AL-335 800 mg QD, ODV 50 mg QOD and SMV 75 mg QD for 8 weeks.

Reporting group title

Cohort 4 (12 Weeks GT1)

Reporting group description

Cohort 4 (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD and ODV 50 mg tablets QOD for 12 weeks.

Reporting group title

Cohort 5a (8 Weeks GT3)

Reporting group description

Cohort 5a (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 8 weeks.

Reporting group title

Cohort 5b (12 Weeks GT3)

Reporting group description

Cohort 5b (Subjects without Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 50 mg tablets QOD and SMV 75 mg tablets QD for 12 weeks.

Reporting group title

Cohort 6,7,8 (8 Weeks GT1 F4)

Reporting group description

Reporting group title

Cohort 9 (12 Weeks GT1 F4)

Reporting group description

Cohort 9 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 25 mg tablets QOD and SMV 75 mg tablets QD for 12 weeks.

Reporting group title

Cohort 11 (12 Weeks GT2 F4)

Reporting group description

Cohort 11 (Subjects with Cirrhosis) received single dose of AL-335 800 mg tablets QD, ODV 25 mg tablets QOD and SMV 75 mg tablets QD for 12 weeks.

Serious adverse events	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 20 (5.00%)	2 / 25 (8.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	2 / 15 (13.33%)	1 / 4 (25.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate Aminotransferase Increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional Cell Carcinoma Urethra
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrioventricular Block
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Cohort 1 (8 Weeks Genotype [GT1])	Cohort 1b + Cohort 4 (8 Weeks GT1)	Cohort 2 (8 Weeks GT1)	Cohort 3 (Subjects with Cirrhosis)	Cohort 4 (12 Weeks GT1)	Cohort 5a (8 Weeks GT3)	Cohort 5b (12 Weeks GT3)	Cohort 6,7,8 (8 Weeks GT1 F4)	Cohort 9 (12 Weeks GT1 F4)	Cohort 11 (12 Weeks GT2 F4)
Total subjects affected by non serious adverse events
subjects affected / exposed	17 / 20 (85.00%)	20 / 25 (80.00%)	14 / 20 (70.00%)	14 / 20 (70.00%)	7 / 8 (87.50%)	4 / 5 (80.00%)	13 / 14 (92.86%)	18 / 30 (60.00%)	10 / 15 (66.67%)	4 / 4 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Vascular disorders
Aortic Aneurysm
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Haematoma
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0
Hot Flush
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0
Hypertension
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0
Phlebitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
General disorders and administration site conditions
Chest Discomfort
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0
Chest Pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	1	0	0	1	0	0	0
Fatigue
subjects affected / exposed	6 / 20 (30.00%)	4 / 25 (16.00%)	2 / 20 (10.00%)	3 / 20 (15.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	6 / 14 (42.86%)	3 / 30 (10.00%)	1 / 15 (6.67%)	2 / 4 (50.00%)
occurrences all number	6	4	2	3	2	0	6	3	1	2
Feeling Abnormal
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Peripheral Swelling
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Swelling
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Vessel Puncture Site Bruise
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	2 / 30 (6.67%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	1	0	0	1	3	0	0
Vessel Puncture Site Haematoma
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Vessel Puncture Site Phlebitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Reproductive system and breast disorders
Vaginal Discharge
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Cough
subjects affected / exposed	1 / 20 (5.00%)	2 / 25 (8.00%)	1 / 20 (5.00%)	2 / 20 (10.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	2 / 30 (6.67%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	2	1	2	1	0	0	2	0	0
Dry Throat
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Dysphonia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Dyspnoea
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Epistaxis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Nasal Congestion
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	1	0
Oropharyngeal Pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	2	1	1	0	0	0
Rhinorrhoea
subjects affected / exposed	2 / 20 (10.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	1	0	0	1	0	0	0	0	0
Sinus Congestion
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0
Sneezing
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Throat Irritation
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Upper-Airway Cough Syndrome
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Psychiatric disorders
Abnormal Dreams
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Anxiety
subjects affected / exposed	2 / 20 (10.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	0	0	0	1	0	0	0
Depressed Mood
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Dysphoria
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Flat Affect
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Insomnia
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	3 / 20 (15.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	3	0	0	0	0	1	0	0
Irritability
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Libido Decreased
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Nightmare
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Panic Attack
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Sleep Disorder
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	2 / 30 (6.67%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0
Investigations
Blood Creatine Phosphokinase Increase
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	2 / 30 (6.67%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	1	0
Blood Pressure Increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1
Ejection Fraction Decreased
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Electrocardiogram Pr Prolongation
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0
Lipase Increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0
Injury, poisoning and procedural complications
Accidental Overdose
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	3 / 20 (15.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	1	3	0	0	0	1	0	0
Chest Injury
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	2 / 20 (10.00%)	2 / 25 (8.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	4 / 30 (13.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	2	1	1	0	0	0	4	0	0
Epicondylitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0
Eye Contusion
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Joint Injury
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Laceration
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	1 / 14 (7.14%)	2 / 30 (6.67%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	2	0	1	1	3	0	0
Ligament Sprain
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	0	0	1	0	0
Limb Injury
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0
Lip Injury
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Muscle Strain
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Scratch
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Skin Abrasion
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	1	0
Sunburn
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Thermal Burn
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	1	1	0	0
Tooth Fracture
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Wound
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Congenital, familial and genetic disorders
Porphyria Non-Acute
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Cardiac disorders
Atrioventricular Block First Degree
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0
Palpitations
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	1	0	0	1	0	0
Supraventricular Tachycardia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Nervous system disorders
Burning Sensation
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Disturbance in Attention
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Dizziness
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	1	1	0	1	1	0	1	0	1	0
Dysgeusia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Headache
subjects affected / exposed	8 / 20 (40.00%)	5 / 25 (20.00%)	2 / 20 (10.00%)	3 / 20 (15.00%)	4 / 8 (50.00%)	2 / 5 (40.00%)	3 / 14 (21.43%)	2 / 30 (6.67%)	2 / 15 (13.33%)	1 / 4 (25.00%)
occurrences all number	9	5	2	3	6	2	3	3	3	1
Hypogeusia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Hyposmia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Lethargy
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	2	0	1	0	0	0
Memory Impairment
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
Migraine
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Paraesthesia
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	1	0	1	0	0	0
Presyncope
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	1	0	0	0	0	0
Sensory Disturbance
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Tension Headache
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Lymphadenopathy
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0
Ear and labyrinth disorders
Ear Discomfort
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0
Ear Pruritus
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Eye disorders
Dry Eye
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Erythema of Eyelid
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Eye Irritation
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0
Eye Pruritus
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0
Vision Blurred
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Visual Impairment
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Abdominal Distension
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Abdominal Pain
subjects affected / exposed	3 / 20 (15.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 30 (3.33%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	3	0	0	0	1	0	1	1	0	1
Abdominal Pain Lower
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Abdominal Pain Upper
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Constipation
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	1	0	0	1	0	0	0	0	0
Dental Caries
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Diarrhoea
subjects affected / exposed	1 / 20 (5.00%)	2 / 25 (8.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 14 (7.14%)	3 / 30 (10.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	1	2	1	0	1	0	1	3	1	0
Dry Mouth
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	1	1	0	0	0	0	0	0	1
Dyspepsia
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	2	0	1	0	0	0
Eructation
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0
Gastrooesophageal Reflux Disease
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Loose Tooth
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Nausea
subjects affected / exposed	2 / 20 (10.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	3 / 30 (10.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	1	0	0	1	0	0	3	0	0
Noninfective Sialoadenitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Salivary Gland Calculus
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Toothache
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	1	1	0	0	1	0	0
Vomiting
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)	1 / 4 (25.00%)
occurrences all number	1	1	0	0	0	0	0	1	1	3
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Dermal Cyst
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Dermatitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Dermatitis Atopic
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Dermatitis Contact
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Eczema
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Erythema
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1
Hand Dermatitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Hyperhidrosis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Mechanical Urticaria
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Night Sweats
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Photosensitivity Reaction
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Pruritus
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	1
Rash
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	1	0	0	1	0	0
Rash Papular
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Rash Pruritic
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Seborrhoeic Dermatitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Skin Fissures
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Renal and urinary disorders
Micturition Urgency
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Polyuria
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0
Renal Colic
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1
Back Pain
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	2 / 20 (10.00%)	1 / 20 (5.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	3 / 14 (21.43%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	2	1	2	0	3	1	0	0
Bursitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Joint Stiffness
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0
Muscle Tightness
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Musculoskeletal Chest Pain
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	1	0	0	1	0	0
Musculoskeletal Pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Musculoskeletal Stiffness
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0
Myalgia
subjects affected / exposed	1 / 20 (5.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	1	1	1	0	1	0	0	1	1	0
Neck Pain
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	1	1	0	1	0
Pain in Extremity
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0
Rotator Cuff Syndrome
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Infections and infestations
Angular Cheilitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0
Bronchitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1
Conjunctivitis
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0
Conjunctivitis Viral
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Folliculitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Furuncle
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	2	0
Gingivitis
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Influenza
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Laryngitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Lower Respiratory Tract Infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	2 / 4 (50.00%)
occurrences all number	0	0	0	1	0	1	1	0	0	2
Pharyngitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Pneumonia
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Rash Pustular
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Respiratory Tract Infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0
Respiratory Tract Infection Viral
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0
Rhinitis
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0
Skin Infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Tonsillitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Tooth Abscess
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0
Tooth Infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0
Upper Respiratory Tract Infection
subjects affected / exposed	6 / 20 (30.00%)	3 / 25 (12.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	3 / 8 (37.50%)	2 / 5 (40.00%)	4 / 14 (28.57%)	3 / 30 (10.00%)	0 / 15 (0.00%)	1 / 4 (25.00%)
occurrences all number	6	4	1	1	3	2	4	3	0	1
Urinary Tract Infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	2 / 30 (6.67%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0
Viral Infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0
Wound Infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0
Metabolism and nutrition disorders
Appetite Disorder
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Decreased Appetite
subjects affected / exposed	0 / 20 (0.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0
Hyperphagia
subjects affected / exposed	1 / 20 (5.00%)	0 / 25 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0
Increased Appetite
subjects affected / exposed	0 / 20 (0.00%)	1 / 25 (4.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	1	0	0	1	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

03 Nov 2015

Name of ACH-3102 was changed to ODV. Subjects with chronic GT3 HCV infection were also included in the study. Added text in the background section to clarify previous clinical experience of SMV. Added dosing regimens in subjects with chronic GT1 HCV infection (Cohort 4) and GT3 HCV infection (Cohort 5). Inclusion Criterion #7 changed to include the additional Cohorts 4 and 5. Added dose regimens for the additional cohorts. Inclusion Criterion #10 changed to clarify collection timeframe from FibroScans (within 6 months from baseline). Explained allocation in Cohorts 2 and 3, and stratification of subjects in Cohorts 2 to 4. Study duration increased from 36 weeks to 37 weeks. Sample size increased from 60 (up to 80) subjects to 100 (up to 120) subjects.

25 Nov 2015

Added text in the background section to include the current clinical experience of AL-335. Updated text in the study design section to clarify actions that might be taken as the study progresses. The amendment also assigned an identifying term to the optional cohort (Cohort 1b). Updated Exclusion Criterion #11 to clarify screening ECG parameter as PR >200 ms and exclusion due to evidence of heart block or bundle branch block. Changed the text in the dose regimen section to clarify that the dose level and frequency of dosing of the study drugs might be modified in the subsequent cohorts, and Cohorts 1b, 2, and 5 might or might not include SMV. Added an additional futility criterion: Any subject with a PR interval >240 ms while on therapy be discontinued from ODV. Updated the text to clarify the management of cardiotoxicity.

22 Jan 2016

Updated the specific elements of the study design (eg, treatment duration, doses, dosing frequency, population, number/size of cohorts) to permit evaluation of varying combinations, which was important to preliminarily determine the optimal dosing regimen(s) for different drug/subject population combinations prior to starting Phase 2b studies. The size of the intensive PK population was increased to reflect the increase in size of the overall study, in case of adding 3 more optional Cohorts 6 to 8. Updated the text in the primary and secondary objectives to reflect that SMV will not be assessed in all cohorts. Added a secondary endpoint: “Effect of various baseline and host disease related characteristics on treatment outcome”. Updated the duration of study period from 37 to 43 weeks, with screening period increased from 35 to 50 days (for maintaining the eligibility of subjects entitled to enroll but delayed due to delay in initiating next cohorts) and planned maximum treatment duration increased from 8 to 12 weeks (to reflect the revised study design elements). Sample size increased from 100 (up to 120) subjects to 120 (up to 180) subjects.

10 May 2016

Changed the eligible subject population to include treatment-experienced subjects. Added a study objective and endpoint to evaluate the effect of prior HCV treatment on efficacy. More cohorts were added to allow the enrollment of additional dosing regimen combinations, which were especially needed if the treatment-experienced subject population was to be explored. The target daily ODV dose was 25 mg/day. In the earlier protocol version, this was achieved by administering 50 mg qod. Updated text to note that when a 25 mg tablet of ODV would be available, this was to be administered daily, to optimize subject compliance and minimize confusion with respect to ODV dosing. Although the effective total daily dose was assumed to be 25 mg qd, lower ODV doses had not been explored; thus, it could not be ruled out that a lower total daily dose of ODV would be equally effective. The lowest available strength for this study was 25 mg; thus, dosing 25 mg qod would allow the Sponsor to explore ODV dosing as low as the equivalent of 12.5 mg qd. The total sample size of the PK population was increased to 250 to reflect the increase in the number of cohorts and to allow for as much of this data to be collected as was possible.

11 May 2016

Modified Inclusion Criterion #12 to avoid unnecessary repetition of FibroScan, as subjects with known cirrhosis based on a historical FibroScan result did not need to undergo a repeat FibroScan evaluation during screening. Added Exclusion Criterion #21 for liver ultrasound (within 6 months) of hepatic mass or lesion concerning for malignancy (subjects with cirrhosis only) to ensure cirrhotic subjects who were at enhanced risk of hepatocellular carcinoma were not inadvertently enrolled. All Schedule of Events tables were updated accordingly. Updated the laboratory evaluation section to collect an optional serum sample after additional subject consent. This sample could be used a backup sample for safety assessments or to measure explore subject characteristics and potential biomarkers.

14 Jul 2016

Updated protocol title to include subjects with chronic GT2 HCV infection with or without compensated Child-Pugh A cirrhosis to reflect the population planned to be studied in the study. Updated treatment in the protocol title to reflect that the subjects may or may not receive SMV. All other instances in the protocol were updated accordingly. Updated protocol title page to include the IND number and the EudraCT number. Updated contact information and the SAE reporting section to allow flexibility in the event that the CRO for pharmacovigilance was changed. Removed reference of treatment-experienced subjects throughout the protocol. Updated number of sites and location to reflect the need to have more subjects enrolled. Added a rationale section to justify inclusion of women of childbearing potential.

26 Jul 2016

IND number was removed. As this study is conducted outside the US, the study is non-IND. Updated the synopsis table to provide clarification of the cohorts. Revised the background section to include a treatment-emergent SAE that was likely unrecognized but present at baseline and inadvertently omitted from prior safety discussion.

13 Sep 2016

Updated definition of sustained virologic failure. Additional post-treatment follow-up was added at Week 18. Clarification added for increase in cohort size, if dosing regimen was modified due to insufficient efficacy or safety, to ensure 20 subjects in each cohort. Updated study design to include maximum VL in case of insufficient efficacy due to dosing regimens, to ensure an adequate risk-benefit profile. Updated status of completed, initiated, and planned cohorts. Study design was updated to reflect current study plan. Updated number of sites, as number of subjects to be enrolled was increased. Updated background section with all available PK, efficacy, and safety data. Updated list of prohibited medications to permit conditional use of QTc prolonging medications.

21 Dec 2016

Updated pharmacovigilance contact details. Updated protocol sections to confirm the status of cohort enrollment as well as confirm that cohort regimens would not change unless necessary for safety purposes. Replaced “randomized/randomization” with “enrolled/enrollment” to correctly reflect the study conduct.

24 Feb 2017

Updated pharmacovigilance contact details. Definition of on-treatment failure and viral relapse were updated for clarity. Study-specific safety, efficacy, and PK data updated to reflect available known information. Contraception-related language updated based on new information available. Exclusion criterion for HbA1c updated based on the central laboratory reporting method. Added study treatment stopping criteria for compliance with the US Food and Drug Administration requirements. All sections related to discontinuation updated accordingly. Schedule of Events tables were updated to reflect changes in liver ultrasound time points and to remove PK sample at 12 hours removed to avoid subject stay at a clinic so late in the night. Added information on analysis of hepatitis B infection in case of ALT flares. Added information related to viral sequencing in the efficacy analysis section.

03 May 2017

Updated study design to include treatment-experienced subjects. A case-by-case review of illicit drug use was added due to small target population. Exclusion criterion for platelet counts broadened to allow enrollment of subjects with cirrhosis. Clarified that the subjects could undergo rescreening to enroll subjects who were screen failures due to minor cutoffs. Missed dose window changed from 24 hours to 12 hours due to change in dose regimen of ODV. Window of 3 days for echocardiogram at the screening visit was removed, as echocardiogram was less likely to change during the screening period because the study drug was not administered.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, ACH-3102, and Simeprevir

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Subjects with Treatment-Emergent Adverse Event (TEAE)

Primary: Number of Subjects with Treatment-Emergent Adverse Event (TEAE)

Primary: Body Weight at End of Treatment

Primary: Body Weight at End of Treatment

Primary: Body Mass Index (BMI) at End of Treatment

Primary: Body Mass Index (BMI) at End of Treatment

Primary: Percentage of Subjects with Worst Post-Baseline Values of Vital Signs

Primary: Percentage of Subjects with Worst Post-Baseline Values of Vital Signs

Primary: Percentage of Subjects with Maximum Decrease from Baseline in Mean Ejection Fraction

Primary: Percentage of Subjects with Maximum Decrease from Baseline in Mean Ejection Fraction

Primary: Percentage of Subjects by Treatment-Emergent Toxicity Grade - Hematology Parameters

Primary: Percentage of Subjects by Treatment-Emergent Toxicity Grade - Hematology Parameters

Primary: Percentage of Subjects by Treatment-Emergent Toxicity Grade - Blood Chemistry Parameters

Primary: Percentage of Subjects by Treatment-Emergent Toxicity Grade - Blood Chemistry Parameters

Primary: Percentage of Subjects by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)

Primary: Percentage of Subjects by Treatment Emergent Toxicity Grade - Prothrombin International Normalized Ratio (INR)

Primary: Percentage of Subject by Treatment-Emergent Toxicity Grade - Urinalysis Parameter - Protien

Primary: Percentage of Subject by Treatment-Emergent Toxicity Grade - Urinalysis Parameter - Protien

Primary: Percentage of Subjects with Worst Treatment-Emergent Abnormalities of Electrocardiogram (ECG) Parameters

Primary: Percentage of Subjects with Worst Treatment-Emergent Abnormalities of Electrocardiogram (ECG) Parameters

Secondary: Percentage of Subjects with Sustained Virologic Response (SVR) at week 4, 12 and 24 After end of Treatment

Secondary: Percentage of Subjects with Sustained Virologic Response (SVR) at week 4, 12 and 24 After end of Treatment

Secondary: Minimum Observed Plasma Concentration (Cmin) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

Secondary: Minimum Observed Plasma Concentration (Cmin) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

Secondary: Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolite (ALS-022399 and ALS-022227)

Secondary: Maximum Observed Plasma Concentration (Cmax) of AL-335 and its Metabolite (ALS-022399 and ALS-022227)

Secondary: Trough Plasma Concentration (Ctrough) for AL-335 and its metabolites (ALS-022399 and ALS-022227)

Secondary: Trough Plasma Concentration (Ctrough) for AL-335 and its metabolites (ALS-022399 and ALS-022227)

Secondary: Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

Secondary: Time to Reach the Maximum Plasma Concentration (Tmax) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

Secondary: Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

Secondary: Area Under the Plasma Concentration-Time Curve From Time 0 to Last Measurable Plasma Concentration (AUC [0-last]) of AL-335 and its metabolites (ALS-022399 and ALS-022227)

Secondary: Area Under the Plasma Concentration Time-Curve at 24 hours (AUC0-24) for AL-335 and its Metabolites (ALS-022399 and ALS-022227)

Secondary: Area Under the Plasma Concentration Time-Curve at 24 hours (AUC0-24) for AL-335 and its Metabolites (ALS-022399 and ALS-022227)

Secondary: Last Measurable Plasma Concentration (Clast) of AL-335 and its Metabolite (ALS-022399 and ALS-022227)

Secondary: Last Measurable Plasma Concentration (Clast) of AL-335 and its Metabolite (ALS-022399 and ALS-022227)

Secondary: Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and its Metabolites (ALS-022399 and ALS-022227)

Secondary: Time Corresponding to Last Measurable Plasma Concentration (Tlast) for AL-335 and its Metabolites (ALS-022399 and ALS-022227)

Secondary: Average Plasma Concentration at Steady State (Css.avg) of ALS-022227

Secondary: Average Plasma Concentration at Steady State (Css.avg) of ALS-022227

Secondary: Cmin of Simeprevir

Secondary: Cmin of Simeprevir

Secondary: Cmax of Simeprevir

Secondary: Cmax of Simeprevir

Secondary: Ctrough of Simeprevir

Secondary: Ctrough of Simeprevir

Secondary: Tmax of Simeprevir

Secondary: Tmax of Simeprevir

Secondary: AUC (0-last) of Simeprevir

Secondary: AUC (0-last) of Simeprevir

Secondary: AUC (0-24) of Simeprevir

Secondary: AUC (0-24) of Simeprevir

Secondary: Clast of Simeprevir

Secondary: Clast of Simeprevir

Secondary: Tlast of Simeprevir

Secondary: Tlast of Simeprevir

Secondary: Average Plasma Concentration at Steady State (Css,avg) of Simeprevir

Secondary: Average Plasma Concentration at Steady State (Css,avg) of Simeprevir

Secondary: Cmin of Odalasvir

Secondary: Cmin of Odalasvir

Secondary: Cmax of Odalasvir

Secondary: Cmax of Odalasvir

Secondary: Ctrough of Odalasvir

Secondary: Ctrough of Odalasvir

Secondary: Tmax of Odalasvir

Secondary: Tmax of Odalasvir

Secondary: AUC (0-last) of Odalasvir

Secondary: AUC (0-last) of Odalasvir

Secondary: AUC (0-24) for Odalasvir

Secondary: AUC (0-24) for Odalasvir

Clinical Trial Results:
A Study to Evaluate the Safety, Pharmacokinetics and Efficacy of the Combination of AL-335, ACH-3102, and Simeprevir