Download PDF

Clinical Trial Results:
A safety, tolerability, pharmacokinetics and efficacy study of RO7049389 in: (1) single- (with or without food) and multiple- (with midazolam) ascending doses in healthy volunteers; (2) patients chronically infected with hepatitis B virus (3) patients with chronic hepatitis B

Summary
EudraCT number	2019-001139-30
Trial protocol	BG
Global end of trial date	16 Mar 2022

Results information
Results version number	v1(current)
This version publication date	31 Mar 2023
First version publication date	31 Mar 2023
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

YP39364

ISRCTN number

US NCT number

NCT02952924

WHO universal trial number (UTN)

Sponsor organisation name

Hoffmann-La Roche

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, 4070

Public contact

Medical Communications, Hoffmann-La Roche, +41 61 688 1111, global.rochegenentechtrials@roche.com

Scientific contact

Medical Communications, Hoffmann-La Roche, +41 61 688 1111, global.rochegenentechtrials@roche.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

16 Mar 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 Mar 2022

Was the trial ended prematurely?

Main objective of the trial

This study was a multicenter, three-part study. Parts 1 and 2 were randomized, investigator- and participant-blinded, placebo-control, single-ascending dose (SAD) and multiple-ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RO7049389 following oral administration in healthy volunteers and chronic HBV infected participants. Part 3 was a non-randomized, non-controlled, open-label part to assess the efficacy and safety of RO7049389 when administered in combination with standard-of-care therapies for up to 48 weeks in nucleos(t)ide (NUC)-suppressed and treatment-naive chronic hepatitis B (CHB) participants.

Protection of trial subjects

Participants were required to sign an Informed Consent Form.

Background therapy

Evidence for comparator

Actual start date of recruitment

14 Dec 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 1

Country: Number of subjects enrolled

Bulgaria: 10

Country: Number of subjects enrolled

China: 18

Country: Number of subjects enrolled

Hong Kong: 22

Country: Number of subjects enrolled

New Zealand: 107

Country: Number of subjects enrolled

Singapore: 5

Country: Number of subjects enrolled

Thailand: 15

Country: Number of subjects enrolled

Taiwan: 14

Worldwide total number of subjects

192

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)

192

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

Healthy volunteers (Part 1); participants with chronic hepatitis B virus (Part 2); treatment-naive or treatment-suppressed participants with chronic hepatitis B virus

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Parts 1a and 1b: Single ascending dose (SAD) Placebo

Arm description

Healthy volunteers (HVs) received a single dose of placebo under fasted (Part 1a) or fed (Part 1b) conditions.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Single dose administered orally

Part 1c: Multiple ascending dose (MAD) Placebo

Arm description

HVs received placebo either once-daily (QD) or twice-daily (BID) for 13 days, followed by a single dose on Day 14.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once-daily (QD) or twice-daily (BID) for 13 days, followed by a single dose on Day 14.

Part 2: Proof-of-Mechanism (POM) Placebo

Arm description

Participants with chronic hepatitis B virus (CHB) infection received placebo once daily (QD) or twice daily (BID) for 27 days, followed by a single dose on Day 28.

Arm type

Experimental

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Administered orally once daily (QD) or twice daily (BID) for 27 days, followed by a single dose on Day 28.

Part 1a: SAD Cohort 1

Arm description

HVs received a single dose of 150 mg of RO7049389 under fasted conditions.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Single oral dose of 150 mg of RO7049389 under fasted conditions.

Part 1a and Part 1b: SAD Cohort 2 (food effect)

Arm description

Part 1a: HVs received a single dose of 450 mg of RO7049389 under fasted conditions. Part 1b: HVs received a single dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions. Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.

Part 1a: SAD Cohort 3

Arm description

HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Single oral dose of 1000 mg of RO7049389 under fasted conditions.

Part 1a: SAD Cohort 4

Arm description

HVs received a single dose of 2000 mg of RO7049389 under fasted conditions.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Single oral dose of 2000 mg of RO7049389 under fasted conditions.

Part 1a: SAD Cohort 5

Arm description

HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Single oral dose of 1000 mg of RO7049389 under fasted conditions.

Part 1a: SAD Cohort 6

Arm description

HVs received a single dose of 2500 mg of RO7049389 under fasted conditions.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Single oral dose of 2500 mg of RO7049389 under fasted conditions.

Part 1c: MAD Cohort 1

Arm description

HVs received 200 mg of RO7049389 BID under fasted conditions for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

200 mg of RO7049389 BID administered orally under fasted conditions for 13 days, followed by a single dose on Day 14.

Investigational medicinal product name

Midazolam

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Single dose of 100 micrograms administered orally on Day -1 and Day 14.

Part 1c: MAD Cohort 2

Arm description

HVs received 200 mg of RO7049389 BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

200 mg of RO7049389 administered orally BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14.

Investigational medicinal product name

Midazolam

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Single dose of 100 micrograms administered orally on Day -1 and Day 14.

Part 1c: MAD Cohort 3

Arm description

HVs received 400 mg of RO7049389 BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14.

Arm type

Experimental

Investigational medicinal product name

Midazolam

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Single dose of 100 micrograms administered orally on Day -1 and Day 14.

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

400 mg of RO7049389 administered orally BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14.

Part 1c: MAD Cohort 4

Arm description

HVs received 800 mg of RO7049389 BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

800 mg of RO7049389 administered orally BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14.

Investigational medicinal product name

Midazolam

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Single dose of 100 micrograms administered orally on Day -1 and Day 14.

Part 1c: MAD Cohort 5

Arm description

HVs received 600 mg of RO7049389 BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

600 mg of RO7049389 administered orally BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14.

Investigational medicinal product name

Midazolam

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

Single dose of 100 micrograms administered orally on Day -1 and Day 14.

Part 2: POM Cohort 1

Arm description

Participants with CHB received 200 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

200 mg of RO7049389 administered orally BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Part 2: POM Cohort 2

Arm description

Participants with CHB received 400 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

400 mg of RO7049389 administered orally BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Part 2: POM Cohort 3

Arm description

Participants with CHB received 600 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

600 mg of RO7049389 administered orally QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Part 2: POM Cohort 4

Arm description

Participants with CHB received 1000 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

1000 mg of RO7049389 administered orally QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Part 2: POM Cohort 5

Arm description

Participants with CHB received 200 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

200 mg of RO7049389 administered orally QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Part 3: Cohort A

Arm description

Nucleos(t)ide (NUC)-suppressed CHB participants received 600 mg of RO7049389 QD under fasted conditions in addition to an NUC (administered per local SoC) for 48 weeks. After the study treatment period, participants either continued NUC for another 24 weeks, or discontinued all treatment.

Arm type

Experimental

Investigational medicinal product name

NUC (entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet, Oral solution

Routes of administration

Oral use

Dosage and administration details

Administered per local label for 48 weeks during the study treatment period, with or without an additional 24 weeks.

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

RO7049389 administered orally for 48 weeks.

Part 3: Cohort B

Arm description

Treatment-naïve immune-active CHB participants 600 mg of RO7049389 QD under fasted conditions for 4 weeks, followed by RO7049389 + NUC (administered per local SoC) for an additional 44 weeks. After the study treatment period, participants either continued NUC for another 24 weeks, or discontinued all treatment.

Arm type

Experimental

Investigational medicinal product name

NUC (entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet, Oral solution

Routes of administration

Oral use

Dosage and administration details

Administered per local label for 44 weeks during the study treatment period, with or without an additional 24 weeks.

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

RO7049389 administered orally for 48 weeks.

Part 3: Cohort C

Arm description

Treatment-naïve immune-active CHB participants received 600 mg of RO7049389 QD under fasted conditions + NUC + pegylated interferon (Peg-IFN) for 48 weeks. After the study treatment period, participants either continued NUC for another 24 weeks, or discontinued all treatment.

Arm type

Experimental

Investigational medicinal product name

RO7049389

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

RO7049389 administered orally for 48 weeks.

Investigational medicinal product name

Pegylated interferon

Investigational medicinal product code

Other name

PEG-IFN

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Administered per local label for 48 weeks

Investigational medicinal product name

NUC (entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet, Oral solution

Routes of administration

Oral use

Dosage and administration details

Administered per local label for 48 weeks during the study treatment period, with or without an additional 24 weeks.

Number of subjects in period 1	Parts 1a and 1b: Single ascending dose (SAD) Placebo	Part 1c: Multiple ascending dose (MAD) Placebo	Part 2: Proof-of-Mechanism (POM) Placebo	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Started	11	10	6	3	6	3	6	6	6	6	7	7	6	6	6	6	6	7	6	32	10	30
Completed	11	10	6	3	6	3	6	6	6	6	7	7	6	6	6	6	6	6	6	31	10	28
Not completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	2
Participant unable to adhere to study schedule	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1
Noncompliance with study drug	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1
Participant refused to adhere to study protocol	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-
Protocol deviation	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-

Baseline characteristics

Top of page

Reporting group title

Parts 1a and 1b: Single ascending dose (SAD) Placebo

Reporting group description

Healthy volunteers (HVs) received a single dose of placebo under fasted (Part 1a) or fed (Part 1b) conditions.

Reporting group title

Part 1c: Multiple ascending dose (MAD) Placebo

Reporting group description

HVs received placebo either once-daily (QD) or twice-daily (BID) for 13 days, followed by a single dose on Day 14.

Reporting group title

Part 2: Proof-of-Mechanism (POM) Placebo

Reporting group description

Participants with chronic hepatitis B virus (CHB) infection received placebo once daily (QD) or twice daily (BID) for 27 days, followed by a single dose on Day 28.

Reporting group title

Part 1a: SAD Cohort 1

Reporting group description

HVs received a single dose of 150 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a and Part 1b: SAD Cohort 2 (food effect)

Reporting group description

Reporting group title

Part 1a: SAD Cohort 3

Reporting group description

HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a: SAD Cohort 4

Reporting group description

HVs received a single dose of 2000 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a: SAD Cohort 5

Reporting group description

HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a: SAD Cohort 6

Reporting group description

HVs received a single dose of 2500 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1c: MAD Cohort 1

Reporting group description

HVs received 200 mg of RO7049389 BID under fasted conditions for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14.

Reporting group title

Part 1c: MAD Cohort 2

Reporting group description

Reporting group title

Part 1c: MAD Cohort 3

Reporting group description

Reporting group title

Part 1c: MAD Cohort 4

Reporting group description

Reporting group title

Part 1c: MAD Cohort 5

Reporting group description

Reporting group title

Part 2: POM Cohort 1

Reporting group description

Participants with CHB received 200 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 2

Reporting group description

Participants with CHB received 400 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 3

Reporting group description

Participants with CHB received 600 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 4

Reporting group description

Participants with CHB received 1000 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 5

Reporting group description

Participants with CHB received 200 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Reporting group title

Part 3: Cohort A

Reporting group description

Reporting group title

Part 3: Cohort B

Reporting group description

Reporting group title

Part 3: Cohort C

Reporting group description

Reporting group values	Parts 1a and 1b: Single ascending dose (SAD) Placebo	Part 1c: Multiple ascending dose (MAD) Placebo	Part 2: Proof-of-Mechanism (POM) Placebo	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C	Total
Number of subjects	11	10	6	3	6	3	6	6	6	6	7	7	6	6	6	6	6	7	6	32	10	30	192
Age categorical
Units: Subjects
Adults (18-64 years)	11	10	6	3	6	3	6	6	6	6	7	7	6	6	6	6	6	7	6	32	10	30	192
Age Continuous
Units: years
arithmetic mean (standard deviation)	26.1 ( 8.4 )	25.2 ( 4.9 )	43.5 ( 6.4 )	32.7 ( 10.1 )	27.3 ( 7.6 )	28.7 ( 13.6 )	26.7 ( 4.7 )	26.7 ( 13.5 )	30.5 ( 7.0 )	25.5 ( 4.5 )	23.9 ( 2.8 )	26.7 ( 3.8 )	28.8 ( 11.1 )	28.3 ( 5.8 )	40.2 ( 8.3 )	34.7 ( 12.1 )	41.5 ( 11.8 )	47.0 ( 6.1 )	40.7 ( 15.3 )	47.2 ( 8.3 )	43.8 ( 9.8 )	32.8 ( 7.7 )	-
Sex: Female, Male
Units: Participants
Female	1	0	3	0	0	0	0	0	0	0	0	0	0	0	1	3	2	4	1	13	5	7	40
Male	10	10	3	3	6	3	6	6	6	6	7	7	6	6	5	3	4	3	5	19	5	23	152
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	1	1	5	0	1	0	0	3	0	1	0	3	1	1	5	5	5	7	5	25	5	28	102
Native Hawaiian or Other Pacific Islander	0	1	1	2	0	0	0	0	0	1	0	0	1	0	0	1	0	0	0	1	1	1	10
Black or African American	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
White	9	7	0	1	5	3	6	3	6	4	7	4	3	4	1	0	1	0	1	6	4	1	76
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1
Unknown or Not Reported	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	2
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	1	2	0	0	0	1	0	0	2	0	1	1	0	1	0	0	0	0	0	0	0	0	9
Not Hispanic or Latino	10	8	6	3	6	2	6	6	4	6	6	6	6	5	6	6	6	7	6	30	9	30	180
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1	0	3

Subject analysis set title

Part 1

Subject analysis set type

Full analysis

Subject analysis set description

Healthy volunteers (HVs) received a single dose (Part 1a and Part 1b) or multiple doses (Part 1c) of RO7049389 or placebo under fasted or fed conditions. Participants in Part 1c additionally received two doses of midazolam.

Subject analysis set title

Part 2

Subject analysis set type

Full analysis

Subject analysis set description

Participants with chronic hepatitis B virus (CHB) infection received RO7049389 or placebo once daily (QD) or twice daily (BID) for 27 days, followed by a single dose on Day 28.

Subject analysis set title

Part 3

Subject analysis set type

Full analysis

Subject analysis set description

Treatment-naive or treatment-suppressed participants with CHB were given RO7049389 + NUC (Cohorts A and B) or RO7049389 + NUC + PEG-IFN (Cohort C) for 48 weeks. After the study treatment period, participants either continued NUC for another 24 weeks, or discontinued all treatment.

Subject analysis sets values	Part 1	Part 2	Part 3
Number of subjects	83	37	72
Age categorical
Units: Subjects
Adults (18-64 years)	83	37	72
Age Continuous
Units: years
arithmetic mean (standard deviation)	( )	( )	( )
Sex: Female, Male
Units: Participants
Female
Male
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino
Not Hispanic or Latino
Unknown or Not Reported

End points

Top of page

Reporting group title

Parts 1a and 1b: Single ascending dose (SAD) Placebo

Reporting group description

Healthy volunteers (HVs) received a single dose of placebo under fasted (Part 1a) or fed (Part 1b) conditions.

Reporting group title

Part 1c: Multiple ascending dose (MAD) Placebo

Reporting group description

HVs received placebo either once-daily (QD) or twice-daily (BID) for 13 days, followed by a single dose on Day 14.

Reporting group title

Part 2: Proof-of-Mechanism (POM) Placebo

Reporting group description

Participants with chronic hepatitis B virus (CHB) infection received placebo once daily (QD) or twice daily (BID) for 27 days, followed by a single dose on Day 28.

Reporting group title

Part 1a: SAD Cohort 1

Reporting group description

HVs received a single dose of 150 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a and Part 1b: SAD Cohort 2 (food effect)

Reporting group description

Reporting group title

Part 1a: SAD Cohort 3

Reporting group description

HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a: SAD Cohort 4

Reporting group description

HVs received a single dose of 2000 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a: SAD Cohort 5

Reporting group description

HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a: SAD Cohort 6

Reporting group description

HVs received a single dose of 2500 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1c: MAD Cohort 1

Reporting group description

HVs received 200 mg of RO7049389 BID under fasted conditions for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14.

Reporting group title

Part 1c: MAD Cohort 2

Reporting group description

Reporting group title

Part 1c: MAD Cohort 3

Reporting group description

Reporting group title

Part 1c: MAD Cohort 4

Reporting group description

Reporting group title

Part 1c: MAD Cohort 5

Reporting group description

Reporting group title

Part 2: POM Cohort 1

Reporting group description

Participants with CHB received 200 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 2

Reporting group description

Participants with CHB received 400 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 3

Reporting group description

Participants with CHB received 600 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 4

Reporting group description

Participants with CHB received 1000 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 5

Reporting group description

Participants with CHB received 200 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Reporting group title

Part 3: Cohort A

Reporting group description

Reporting group title

Part 3: Cohort B

Reporting group description

Reporting group title

Part 3: Cohort C

Reporting group description

Subject analysis set title

Part 1

Subject analysis set type

Full analysis

Subject analysis set description

Subject analysis set title

Part 2

Subject analysis set type

Full analysis

Subject analysis set description

Participants with chronic hepatitis B virus (CHB) infection received RO7049389 or placebo once daily (QD) or twice daily (BID) for 27 days, followed by a single dose on Day 28.

Subject analysis set title

Part 3

Subject analysis set type

Full analysis

Subject analysis set description

Primary: Part 1: Percentage of Participants With Adverse Events

Top of page

End point title

Part 1: Percentage of Participants With Adverse Events ^[1] ^[2]

End point description

End point type

Primary

End point timeframe

Up to Day 29 (Part 1a), Day 44 (Part 1b), Day 42 (Part 1c)

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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Parts 1a and 1b: Single ascending dose (SAD) Placebo	Part 1c: Multiple ascending dose (MAD) Placebo	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5
Number of subjects analysed	11	10	3	6	3	6	6	6	6	7	7	6	6
Units: Percentage of participants
number (not applicable)	27.3	60.0	33.3	50.0	100	83.3	33.3	50.0	83.3	57.1	28.6	16.7	16.7

No statistical analyses for this end point

Primary: Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389

Top of page

End point title

Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389 ^[3] ^[4]

End point description

9999 = No data collected for fed state because cohort was only in fasted state

End point type

Primary

End point timeframe

Up to 28 days

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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6
Number of subjects analysed	3	6	3	6	6	6
Units: Hours
median (full range (min-max))
Fasted	2.0 (2.0 to 2.0)	1.25 (1.0 to 2.0)	1.5 (1.5 to 3.0)	2.0 (1.5 to 3.0)	1.5 (1.5 to 3.0)	3.0 (1.5 to 4.0)
Fed	9999 (9999 to 9999)	3.0 (1.5 to 4.0)	9999 (9999 to 9999)	9999 (9999 to 9999)	9999 (9999 to 9999)	9999 (9999 to 9999)

No statistical analyses for this end point

Primary: Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389

Top of page

End point title

Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 ^[5] ^[6]

End point description

9999 = No data collected for fed state because cohort was only in fasted state

End point type

Primary

End point timeframe

Up to 28 days

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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6
Number of subjects analysed	3	6	3	6	6	6
Units: ng/mL
geometric mean (geometric coefficient of variation)
Fasted	250 ( 33.4 )	1900 ( 79.7 )	8990 ( 77.4 )	14700 ( 67.6 )	8990 ( 77.4 )	24800 ( 63.9 )
Fed	9999 ( 9999 )	4610 ( 75.6 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Primary: Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389

Top of page

End point title

Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389 ^[7] ^[8]

End point description

9999 = No data collected for fed state because cohort was only in fasted state

End point type

Primary

End point timeframe

Up to 28 days

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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6
Number of subjects analysed	3	6	3	6	6	6
Units: ng/mL
geometric mean (geometric coefficient of variation)
Fasted	879 ( 7.5 )	4690 ( 53.2 )	34400 ( 71.6 )	46300 ( 62.0 )	34400 ( 71.6 )	134000 ( 91.4 )
Fed	9999 ( 9999 )	10900 ( 71.9 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Primary: Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389

Top of page

End point title

Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389 ^[9] ^[10]

End point description

9999 = No data collected for fed state because cohort was only in fasted state

End point type

Primary

End point timeframe

Up to 28 days

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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6
Number of subjects analysed	3	6	3	6	6	6
Units: ng/mL
geometric mean (geometric coefficient of variation)
Fasted	868 ( 6.6 )	4660 ( 53.8 )	34300 ( 71.6 )	46200 ( 62.1 )	34300 ( 71.6 )	134000 ( 91.4 )
Fed	9999 ( 9999 )	10900 ( 72.0 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Primary: Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389

Top of page

End point title

Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389 ^[11] ^[12]

End point description

9999 = No data collected for fed state because cohort was only in fasted state

End point type

Primary

End point timeframe

Up to Day 28

Notes
[11] - 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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6
Number of subjects analysed	3	6	3	6	6	6
Units: Hours
geometric mean (geometric coefficient of variation)
Fasted	3.34 ( 35.3 )	8.80 ( 81.1 )	7.23 ( 39.5 )	12.1 ( 52.1 )	7.23 ( 39.5 )	12.4 ( 44.7 )
Fed	9999 ( 9999 )	4.20 ( 32.0 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Primary: Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389

Top of page

End point title

Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 ^[13] ^[14]

End point description

9999 = No data collected for fed state because cohort was only in fasted state

End point type

Primary

End point timeframe

Up to Day 28

Notes
[13] - 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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6
Number of subjects analysed	3	6	3	6	6	6
Units: ng/mL
geometric mean (geometric coefficient of variation)
Fasted	171 ( 7.3 )	128 ( 67.8 )	64.9 ( 130.3 )	63.3 ( 69.7 )	64.9 ( 130.3 )	69.7 ( 122.3 )
Fed	9999 ( 9999 )	61.5 ( 72.1 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Primary: Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389

Top of page

End point title

Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389 ^[15] ^[16]

End point description

999 = Data unavailable because this parameter was not measured for this cohort. 9999 = No data collected for fed state because cohort was only in fasted state

End point type

Primary

End point timeframe

Up to Day 28

Notes
[15] - 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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6
Number of subjects analysed	3	6	3	6	6	6
Units: ng/mL
geometric mean (geometric coefficient of variation)
Fasted	999 ( 999 )	0.312 ( 69.6 )	1.88 ( 83.9 )	3.56 ( 92.0 )	1.88 ( 83.9 )	6.89 ( 101.8 )
Fed	9999 ( 9999 )	999 ( 999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Primary: Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389

Top of page

End point title

Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389 ^[17] ^[18]

End point description

999 = Data unavailable because this parameter was not measured for this cohort. 9999 = No data collected for fed state because cohort was only in fasted state

End point type

Primary

End point timeframe

Up to Day 28

Notes
[17] - 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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a: SAD Cohort 1	Part 1a and Part 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6
Number of subjects analysed	3	6	3	6	6	6
Units: ng/mL
geometric mean (geometric coefficient of variation)
Fasted	999 ( 999 )	1.60 ( 84.8 )	1.55 ( 42.9 )	1.41 ( 18.7 )	1.55 ( 42.9 )	0.82 ( 22.8 )
Fed	9999 ( 9999 )	999 ( 999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )	9999 ( 9999 )

No statistical analyses for this end point

Primary: Part 2: Percentage of Participants With Adverse Events

Top of page

End point title

Part 2: Percentage of Participants With Adverse Events ^[19] ^[20]

End point description

End point type

Primary

End point timeframe

Up to Day 112

Notes
[19] - 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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 2: Proof-of-Mechanism (POM) Placebo	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Number of subjects analysed	6	6	6	6	7	6
Units: Percentage of participants
number (not applicable)	50.0	66.7	66.7	83.3	57.1	33.3

No statistical analyses for this end point

Primary: Part 2: Quantitative Plasma HBV DNA Level

Top of page

End point title

Part 2: Quantitative Plasma HBV DNA Level ^[21] ^[22]

End point description

End point type

Primary

End point timeframe

Baseline - Day 112

Notes
[21] - 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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 2: Proof-of-Mechanism (POM) Placebo	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Number of subjects analysed	6 ^[23]	6 ^[24]	6 ^[25]	6	7 ^[26]	6
Units: Log10 IU/mL
median (full range (min-max))
Baseline	5.94 (4.8 to 8.2)	4.50 (1.9 to 8.3)	7.80 (4.0 to 8.5)	4.43 (3.3 to 8.4)	5.10 (4.1 to 8.7)	7.14 (3.9 to 8.5)
Day 8	5.25 (4.6 to 7.8)	1.40 (1.3 to 4.8)	5.27 (1.8 to 6.2)	1.75 (1.3 to 5.7)	2.25 (1.3 to 6.5)	5.21 (2.0 to 6.0)
Day 15	5.29 (4.3 to 8.1)	2.00 (1.3 to 5.4)	4.58 (1.4 to 6.0)	1.46 (1.3 to 5.5)	1.30 (1.3 to 6.0)	4.90 (1.3 to 5.6)
Day 22	5.16 (3.8 to 8.0)	1.83 (1.3 to 5.1)	4.11 (1.3 to 5.8)	1.41 (1.3 to 5.2)	1.41 (1.3 to 5.6)	4.65 (1.3 to 5.4)
Day 28	5.29 (3.6 to 8.0)	1.65 (1.3 to 4.9)	3.64 (1.3 to 5.8)	1.30 (1.3 to 4.9)	1.30 (1.3 to 5.5)	4.43 (1.3 to 5.4)
Day 35/Follow-up Day 7	5.29 (2.7 to 8.0)	3.23 (1.3 to 8.0)	5.50 (2.8 to 6.6)	2.61 (1.5 to 6.9)	2.98 (2.4 to 6.7)	6.29 (2.4 to 7.6)
Day 56/Follow-up Day 28	5.21 (2.7 to 8.1)	4.07 (2.4 to 8.3)	6.53 (3.3 to 8.2)	3.43 (2.8 to 9.1)	4.04 (3.1 to 8.3)	7.07 (3.9 to 8.3)
Day 84/Follow-up Day 56	5.15 (2.6 to 8.2)	5.76 (2.4 to 8.0)	5.68 (4.4 to 8.1)	4.29 (3.5 to 8.2)	4.73 (3.7 to 8.5)	6.83 (3.8 to 8.4)
Day 112/Follow-up Day 84	5.09 (3.0 to 8.0)	5.89 (3.2 to 7.9)	6.17 (4.1 to 8.2)	4.45 (3.2 to 8.4)	4.55 (4.0 to 8.4)	7.03 (3.8 to 8.3)

Notes
[23] - Days 8-112 n=5
[24] - Day 8 n=5 Days 84,112 n=4
[25] - Day 84 n=5
[26] - Days 8-22, 56-112 n=6 Days 28, 35 n=5

No statistical analyses for this end point

Primary: Part 3: Proportion of patients achieving functional cure

Top of page

End point title

Part 3: Proportion of patients achieving functional cure ^[27] ^[28]

End point description

Functional cure is defined as HBV DNA < lower limit of quantification (LLOQ, 20 IU/mL) with HBsAg loss (< 0.05 IU/mL) at 24 weeks post-treatment.

End point type

Primary

End point timeframe

Every 2-4 weeks from Baseline through Week 72

Notes
[27] - 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: Statistical summaries for each endpoint are descriptive with no planned formal analyses.
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32	10	30
Units: Percentage
number (confidence interval 95%)
Baseline	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 2	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 4	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 8	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 12	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 16	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 20	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 24	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 28	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 32	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 36	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 40	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 44	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 48	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 50	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 52	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 54	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 56	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 58	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 60	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 64	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 68	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)
Week 72	0 (0 to 0.11)	0 (0 to 0.31)	0 (0 to 0.12)

No statistical analyses for this end point

Secondary: Part 1b: Food effect on Cmax of RO7049389

Top of page

End point title

Part 1b: Food effect on Cmax of RO7049389 ^[29]

End point description

This endpoint presents the geometric mean ratio (fed/fasted).

End point type

Secondary

End point timeframe

Day 16

Notes
[29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a and Part 1b: SAD Cohort 2 (food effect)
Number of subjects analysed	6
Units: ng/mL
geometric mean (confidence interval 90%)	2.42 (1.48 to 3.95)

No statistical analyses for this end point

Secondary: Part 1b: Food effect on AUCinf of RO7049389

Top of page

End point title

Part 1b: Food effect on AUCinf of RO7049389 ^[30]

End point description

This endpoint presents the geometric mean ratio (fed/fasted).

End point type

Secondary

End point timeframe

Day 16

Notes
[30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1a and Part 1b: SAD Cohort 2 (food effect)
Number of subjects analysed	6
Units: h*ng/mL
geometric mean (confidence interval 90%)	2.17 (1.39 to 3.40)

No statistical analyses for this end point

Secondary: Part 1c: Cmax of Midazolam

Top of page

End point title

Part 1c: Cmax of Midazolam ^[31]

End point description

This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389).

End point type

Secondary

End point timeframe

Up to Day 14

Notes
[31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 5
Number of subjects analysed	6	6	6	6
Units: pg/mL
geometric mean (confidence interval 90%)	0.892 (0.663 to 1.20)	1.01 (0.846 to 1.21)	1.12 (0.915 to 1.37)	0.940 (0.734 to 1.21)

No statistical analyses for this end point

Secondary: Part 1c: AUCinf of Midazolam

Top of page

End point title

Part 1c: AUCinf of Midazolam ^[32]

End point description

This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389).

End point type

Secondary

End point timeframe

Up to Day 14

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 5
Number of subjects analysed	6	6	6	6
Units: hr*pg/mL
geometric mean (confidence interval 90%)	1.10 (0.846 to 1.42)	1.18 (1.06 to 1.31)	1.25 (1.04 to 1.50)	1.16 (0.993 to 1.36)

No statistical analyses for this end point

Secondary: Part 1c: Tmax of RO7049389

Top of page

End point title

Part 1c: Tmax of RO7049389 ^[33]

End point description

End point type

Secondary

End point timeframe

Up to Day 14

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5
Number of subjects analysed	6	7 ^[34]	7 ^[35]	6 ^[36]	6
Units: hours
median (full range (min-max))
Day 1	2.0 (1.5 to 3.0)	2.0 (1.5 to 3.0)	3.0 (1.5 to 4.0)	3.0 (3.0 to 4.0)	3.0 (2.0 to 3.0)
Day 14	1.5 (1.0 to 1.5)	2.0 (1.5 to 4.0)	3.0 (1.5 to 4.0)	9999 (9999 to 9999)	3.0 (3.0 to 4.0)

Notes
[34] - Day 14 n = 6
[35] - Day 14 n = 6
[36] - 9999 = No data collected for Day 14

No statistical analyses for this end point

Secondary: Part 1c: Cmax of RO7049389

Top of page

End point title

Part 1c: Cmax of RO7049389 ^[37]

End point description

End point type

Secondary

End point timeframe

Up to Day 14

Notes
[37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5
Number of subjects analysed	6	7 ^[38]	7 ^[39]	6 ^[40]	6
Units: ng/mL
geometric mean (geometric coefficient of variation)
Day 1	483 ( 42.5 )	840 ( 41.7 )	4840 ( 53.7 )	14500 ( 39.5 )	10600 ( 42.2 )
Day 14	735 ( 19.9 )	583 ( 41.3 )	2720 ( 49.0 )	9999 ( 9999 )	9960 ( 32.7 )

Notes
[38] - Day 14 n = 6
[39] - Day 14 n = 6
[40] - 9999 = No data collected for Day 14

No statistical analyses for this end point

Secondary: Part 1c: AUC0-12hr of RO7049389

Top of page

End point title

Part 1c: AUC0-12hr of RO7049389 ^[41]

End point description

End point type

Secondary

End point timeframe

Up to Day 14

Notes
[41] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5
Number of subjects analysed	6	7 ^[42]	7 ^[43]	6 ^[44]	6
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)
Day 1	1304.09 ( 31.9 )	1819.92 ( 46.1 )	9760.31 ( 55.7 )	32459.87 ( 42.6 )	27041.94 ( 33.6 )
Day 14	1806.59 ( 25.6 )	1573.32 ( 27.5 )	6511.21 ( 29.0 )	9999 ( 9999 )	28051.71 ( 32.5 )

Notes
[42] - Day 14 n = 6
[43] - Day 14 n = 6
[44] - 9999 = No data collected for Day 14

No statistical analyses for this end point

Secondary: Part 1c: CLr of RO7049389

Top of page

End point title

Part 1c: CLr of RO7049389 ^[45]

End point description

End point type

Secondary

End point timeframe

Up to Day 14

Notes
[45] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5
Number of subjects analysed	6	7 ^[46]	7 ^[47]	6 ^[48]	6
Units: mL/min
geometric mean (geometric coefficient of variation)
Day 1	1.06 ( 74.2 )	1.08 ( 82.6 )	1.43 ( 27.0 )	2.04 ( 54.7 )	1.19 ( 48.6 )
Day 14	1.96 ( 75.2 )	1.87 ( 51.7 )	3.01 ( 46.9 )	9999 ( 9999 )	2.32 ( 35.0 )

Notes
[46] - Day 14 n = 6
[47] - Day 14 n = 6
[48] - 9999 = No data collected for Day 14

No statistical analyses for this end point

Secondary: Part 1c: Accumulation Ratio of RO7049389

Top of page

End point title

Part 1c: Accumulation Ratio of RO7049389 ^[49]

End point description

This endpoint presents the geometric mean ratio (fed/fasted).

End point type

Secondary

End point timeframe

Day 14

Notes
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 5
Number of subjects analysed	6	7	7	6
Units: None
geometric mean (geometric coefficient of variation)	1.45 ( 24.3 )	1.05 ( 31.1 )	0.880 ( 35.6 )	1.09 ( 37.4 )

No statistical analyses for this end point

Secondary: Part 1c: T1/2 of RO7049389

Top of page

End point title

Part 1c: T1/2 of RO7049389 ^[50]

End point description

End point type

Secondary

End point timeframe

Up to Day 14

Notes
[50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5
Number of subjects analysed	6	7 ^[51]	7 ^[52]	6 ^[53]	6
Units: Hours
geometric mean (geometric coefficient of variation)
Day 1	2.27 ( 24.1 )	2.44 ( 12.6 )	2.09 ( 18.5 )	1.70 ( 30.4 )	1.53 ( 22.5 )
Day 14	5.79 ( 40.7 )	5.17 ( 26.8 )	5.08 ( 10.5 )	9999 ( 9999 )	5.73 ( 28.9 )

Notes
[51] - Day 14 n = 6
[52] - Day 14 n = 6
[53] - 9999 = No data collected for Day 14

No statistical analyses for this end point

Secondary: Part 1c: Ae of RO7049389

Top of page

End point title

Part 1c: Ae of RO7049389 ^[54]

End point description

End point type

Secondary

End point timeframe

Up to Day 14

Notes
[54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5
Number of subjects analysed	6	7 ^[55]	7 ^[56]	6 ^[57]	6
Units: mg
geometric mean (geometric coefficient of variation)
Day 1	0.0926 ( 90.7 )	0.0900 ( 56.0 )	0.859 ( 60.9 )	3.58 ( 63.4 )	1.77 ( 35.9 )
Day 14	0.243 ( 89.5 )	0.189 ( 60.7 )	1.26 ( 53.8 )	9999 ( 9999 )	3.68 ( 26.3 )

Notes
[55] - Day 14 n = 6
[56] - Day 14 n = 6
[57] - 9999 = No data collected for Day 14

No statistical analyses for this end point

Secondary: Part 1c: Ctrough of RO7049389

Top of page

End point title

Part 1c: Ctrough of RO7049389 ^[58]

End point description

End point type

Secondary

End point timeframe

Day 14

Notes
[58] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 5
Number of subjects analysed	6	7 ^[59]	7 ^[60]	6
Units: ng/mL
geometric mean (geometric coefficient of variation)	12.1 ( 45.1 )	15.2 ( 27.8 )	42.1 ( 12.8 )	88.9 ( 27.6 )

Notes
[59] - Day 14 n = 6
[60] - Day 14 n = 6

No statistical analyses for this end point

Secondary: Part 2: HBV DNA < Lower Limit of Quantification (LLOQ)

Top of page

End point title

Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) ^[61]

End point description

End point type

Secondary

End point timeframe

Baseline - Day 112/Follow-up Day 84

Notes
[61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 2: Proof-of-Mechanism (POM) Placebo	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Number of subjects analysed	6 ^[62]	6 ^[63]	6 ^[64]	6	7 ^[65]	6
Units: Percentage of participants
number (not applicable)
Baseline	0	0	0	0	0	0
Day 8	0	0	33.3	0	50.0	28.6
Day 15	16.7	0	50.0	0	50.0	57.1
Day 22	16.7	0	50.0	0	50.0	42.9
Day 28	16.7	0	50.0	16.7	66.7	57.1
Day 35/Follow-up Day 7	0	0	16.7	0	0	0
Day 56/Follow-up Day 28	0	0	0	0	0	0
Day 84/Follow-up Day 56	0	0	0	0	0	0
Day 112/Follow-up Day 84	0	0	0	0	0	0

Notes
[62] - Days 8-112 n=5
[63] - Day 8 n=5 Days 84, 112 n=4
[64] - Day 84 n=5
[65] - Days 8-112 n=6

No statistical analyses for this end point

Secondary: Part 2: Tmax of RO7049389

Top of page

End point title

Part 2: Tmax of RO7049389 ^[66]

End point description

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Number of subjects analysed	6	6	6	6	6
Units: Hours
median (full range (min-max))
Day 1	2.0 (2.0 to 3.0)	3.0 (2.0 to 3.0)	1.97 (0.92 to 3.0)	1.98 (1.92 to 3.03)	1.5 (1.0 to 2.87)
Day 28	2.5 (1.08 to 3.0)	2.5 (2.0 to 4.0)	2.0 (0.97 to 3.0)	2.03 (1.90 to 2.85)	1.5 (0.833 to 3.0)

No statistical analyses for this end point

Secondary: Part 2: Cmax of RO7049389

Top of page

End point title

Part 2: Cmax of RO7049389 ^[67]

End point description

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[67] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Number of subjects analysed	6	6	6	6	6
Units: ng/mL
geometric mean (geometric coefficient of variation)
Day 1	1450 ( 69.1 )	8110 ( 59.7 )	5030 ( 42.7 )	23900 ( 41.8 )	910 ( 89.1 )
Day 28	1500 ( 60.3 )	8580 ( 63.7 )	4890 ( 76.9 )	29800 ( 15.2 )	998 ( 52.8 )

No statistical analyses for this end point

Secondary: Part 2: AUCtau of RO7049389

Top of page

End point title

Part 2: AUCtau of RO7049389 ^[68]

End point description

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Number of subjects analysed	6	6	6	6	6
Units: ng*hr/mL
geometric mean (geometric coefficient of variation)
Day 1	2870 ( 50.2 )	19900 ( 78.6 )	11500 ( 65.5 )	80000 ( 71.2 )	3500 ( 76.7 )
Day 28	3350 ( 47.7 )	22400 ( 70.5 )	14600 ( 78.0 )	133000 ( 50.0 )	3480 ( 56.9 )

No statistical analyses for this end point

Secondary: Part 2: Accumulation Ratio of RO7049389

Top of page

End point title

Part 2: Accumulation Ratio of RO7049389 ^[69]

End point description

This endpoint presents the geometric mean ratio (fed/fasted).

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Number of subjects analysed	6	6	6	6	6
Units: None
geometric mean (geometric coefficient of variation)	1.01 ( 81.3 )	0.971 ( 58.2 )	1.65 ( 109.8 )	0.823 ( 77.0 )	0.917 ( 40.9 )

No statistical analyses for this end point

Secondary: Part 2: T1/2 of RO7049389

Top of page

End point title

Part 2: T1/2 of RO7049389 ^[70]

End point description

End point type

Secondary

End point timeframe

Up to Day 28

Notes
[70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Number of subjects analysed	6	6	6	6	6
Units: Hours
geometric mean (geometric coefficient of variation)
Day 1	1.68 ( 18.0 )	1.15 ( 27.6 )	1.09 ( 22.4 )	1.40 ( 34.5 )	2.33 ( 55.2 )
Day 28	3.38 ( 24.1 )	3.26 ( 28.8 )	3.70 ( 26.1 )	2.33 ( 20.1 )	3.81 ( 24.6 )

No statistical analyses for this end point

Secondary: Part 2: Ctrough of RO7049389

Top of page

End point title

Part 2: Ctrough of RO7049389 ^[71]

End point description

End point type

Secondary

End point timeframe

Day 28

Notes
[71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Number of subjects analysed	6	6	6	6	6
Units: ng/mL
geometric mean (geometric coefficient of variation)	26.7 ( 72.7 )	68.2 ( 89.2 )	7.94 ( 60.6 )	27.0 ( 42.3 )	3.37 ( 88.1 )

No statistical analyses for this end point

Secondary: Part 3: Percentage of Participants with AEs

Top of page

End point title

Part 3: Percentage of Participants with AEs ^[72]

End point description

End point type

Secondary

End point timeframe

72 weeks

Notes
[72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32	10	30
Units: Percentage of participants
number (not applicable)	68.8	90	100

No statistical analyses for this end point

Secondary: Part 3: Hepatitis B Surface Antigen (HBsAg) Level

Top of page

End point title

Part 3: Hepatitis B Surface Antigen (HBsAg) Level ^[73]

End point description

End point type

Secondary

End point timeframe

Baseline - Week 72

Notes
[73] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32 ^[74]	10 ^[75]	30 ^[76]
Units: Log10 IU/mL
median (full range (min-max))
Baseline	3.04 (2.48 to 4.30)	3.51 (2.44 to 4.63)	4.10 (2.50 to 5.49)
Week 2	3.08 (2.42 to 4.36)	3.51 (2.53 to 4.69)	4.14 (2.18 to 5.63)
Week 4	3.08 (2.52 to 4.33)	3.47 (2.36 to 4.46)	3.98 (1.74 to 5.55)
Week 8	3.00 (2.41 to 4.33)	3.49 (2.30 to 4.25)	3.62 (1.34 to 5.06)
Week 12	3.02 (2.42 to 4.31)	3.52 (2.51 to 4.25)	3.55 (1.44 to 4.82)
Week 16	3.03 (2.59 to 4.28)	3.22 (2.64 to 4.25)	3.44 (1.56 to 4.46)
Week 20	3.05 (2.54 to 4.30)	3.48 (2.79 to 4.26)	3.26 (1.47 to 4.37)
Week 24	2.99 (2.58 to 4.25)	3.84 (2.85 to 4.23)	3.15 (0.98 to 4.30)
Week 28	3.04 (2.58 to 4.27)	3.39 (2.81 to 4.29)	3.10 (1.04 to 4.33)
Week 32	2.99 (2.54 to 4.28)	3.52 (3.12 to 4.32)	3.09 (0.82 to 4.27)
Week 36	2.98 (2.47 to 4.32)	3.50 (2.85 to 4.20)	2.93 (0.83 to 4.21)
Week 40	3.03 (2.52 to 4.26)	3.81 (2.80 to 4.21)	2.91 (0.80 to 4.24)
Week 44	3.00 (2.50 to 4.23)	3.81 (2.84 to 4.24)	2.91 (0.38 to 4.20)
Week 48	2.99 (2.50 to 4.23)	3.53 (2.81 to 4.18)	2.90 (0.05 to 4.15)
Week 50	2.96 (2.55 to 4.21)	3.21 (3.18 to 3.24)	0.83 (0.21 to 1.72)
Week 52	2.89 (2.55 to 4.24)	3.21 (3.20 to 3.23)	1.32 (0.37 to 1.78)
Week 54	2.98 (2.53 to 4.29)	3.51 (3.16 to 3.89)	1.41 (0.36 to 2.02)
Week 56	2.97 (2.48 to 4.21)	3.75 (2.82 to 4.20)	2.86 (0.45 to 4.25)
Week 58	2.67 (2.52 to 4.23)	3.15 (3.15 to 3.15)	1.70 (0.48 to 2.19)
Week 60	3.84 (2.52 to 4.22)	3.20 (3.16 to 3.23)	1.79 (0.50 to 2.25)
Week 64	2.98 (2.50 to 4.23)	3.53 (2.85 to 4.00)	2.83 (0.76 to 4.85)
Week 68	2.65 (2.56 to 2.74)	3.12 (3.12 to 3.12)	1.84 (1.00 to 2.46)
Week 72	2.95 (2.49 to 4.17)	3.71 (2.83 to 4.23)	2.75 (0.78 to 4.30)

Notes
[74] - Weeks: 2,4,64,72: n=31 8-48, 56: n=30 50: n=11 52: n=10 54: n=9 58: n=3 60: n=6 68: n=2
[75] - Weeks: 16,24,40,44,56,72: n=9 32,64: n=8 50,52,60: n=2 54: n=4 58,68: n=1
[76] - Weeks: 2,8,16-32: n=29 36-48, 56, 64, 72: n=28 50-54, 58, 60, 68: n=5

No statistical analyses for this end point

Secondary: Part 3: Hepatitis B e-Antigen (HBeAg) Levels

Top of page

End point title

Part 3: Hepatitis B e-Antigen (HBeAg) Levels ^[77]

End point description

The population for this endpoint included participants in Part 3 that were HBeAg+ at baseline. 9999 = No participants analyzed for that timepoint.

End point type

Secondary

End point timeframe

Baseline - Week 72

Notes
[77] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	11 ^[78]	6 ^[79]	19 ^[80]
Units: Log10 IU/mL
median (full range (min-max))
Baseline	0.17 (-0.54 to 1.93)	1.07 (0.00 to 2.44)	2.84 (1.48 to 3.49)
Week 2	0.16 (-0.54 to 2.31)	1.01 (-0.89 to 2.31)	2.79 (1.16 to 3.55)
Week 4	0.17 (-0.54 to 2.01)	0.60 (-0.89 to 1.96)	2.57 (0.65 to 3.36)
Week 8	0.15 (-0.54 to 1.78)	0.33 (-0.89 to 1.19)	2.24 (0.24 to 2.80)
Week 12	0.12 (-0.54 to 1.74)	0.17 (-0.89 to 0.57)	2.02 (0.20 to 2.55)
Week 16	0.12 (-0.54 to 1.71)	-0.04 (-0.89 to 0.39)	1.81 (-0.24 to 2.36)
Week 20	0.06 (-0.54 to 1.55)	-0.12 (-0.89 to 0.37)	1.40 (-0.89 to 2.25)
Week 24	0.10 (-0.54 to 1.38)	-0.24 (-0.89 to 0.38)	1.31 (-0.89 to 2.10)
Week 28	0.12 (-0.54 to 1.39)	-0.32 (-0.89 to 0.28)	1.32 (-0.89 to 2.03)
Week 32	0.14 (-0.54 to 1.14)	-0.40 (-0.89 to 0.38)	1.12 (-0.89 to 1.97)
Week 36	0.15 (-0.54 to 1.21)	-0.43 (-0.89 to 0.29)	0.96 (-0.89 to 1.89)
Week 40	0.13 (-0.54 to 1.16)	-0.49 (-0.89 to 0.21)	0.83 (-0.89 to 1.82)
Week 44	0.16 (-0.54 to 1.14)	-0.50 (-0.89 to 0.34)	0.82 (-0.89 to 1.75)
Week 48	0.15 (-0.54 to 1.16)	-0.52 (-0.89 to 0.20)	0.69 (-0.89 to 1.79)
Week 50	-0.53 (-0.54 to -0.52)	-0.71 (-0.89 to -0.54)	-0.47 (-0.47 to -0.47)
Week 52	-0.54 (-0.54 to -0.54)	-0.71 (-0.89 to -0.54)	-0.54 (-0.54 to -0.54)
Week 54	-0.54 (-0.54 to -0.54)	-0.54 (-0.54 to -0.54)	-0.49 (-0.49 to -0.49)
Week 56	0.09 (-0.54 to 1.22)	-0.54 (-0.89 to 0.22)	0.74 (-0.89 to 2.08)
Week 58	9999 (9999 to 9999)	-0.54 (-0.54 to -0.54)	1.23 (1.23 to 1.23)
Week 60	9999 (9999 to 9999)	-0.54 (-0.54 to -0.54)	1.70 (1.70 to 1.70)
Week 64	0.14 (-0.54 to 1.21)	-0.54 (-0.89 to -0.30)	0.36 (-0.89 to 2.96)
Week 68	9999 (9999 to 9999)	-0.54 (-0.54 to -0.54)	-0.54 (-0.54 to -0.54)
Week 72	0.08 (-0.54 to 1.16)	-0.35 (-0.89 to 0.36)	-0.23 (-0.89 to 1.96)

Notes
[78] - Weeks: 50, 52: n=2 54: n=1 58,60,68: n=0
[79] - Weeks: 40, 72: n=5 50-54: n=2 58, 60, 68: n=1 64: n=4
[80] - Weeks: 16-48, 56, 64, 72: n=18 50-54, 58, 60, 68: n=1

No statistical analyses for this end point

Secondary: Part 3: HBV RNA level

Top of page

End point title

Part 3: HBV RNA level ^[81]

End point description

End point type

Secondary

End point timeframe

Baseline - Week 72

Notes
[81] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32 ^[82]	10 ^[83]	30 ^[84]
Units: Log10 copies/mL
median (full range (min-max))
Baseline	0.99 (0.69 to 4.45)	4.02 (0.69 to 6.24)	5.30 (0.69 to 7.50)
Week 2	0.69 (0.69 to 1.79)	1.04 (0.69 to 3.93)	2.37 (0.69 to 4.53)
Week 4	0.69 (0.69 to 1.35)	0.84 (0.69 to 2.90)	1.93 (0.69 to 4.97)
Week 8	0.69 (0.69 to 2.45)	0.69 (0.69 to 1.68)	1.54 (0.69 to 7.03)
Week 12	0.69 (0.69 to 2.64)	0.69 (0.69 to 0.99)	0.99 (0.69 to 3.37)
Week 16	0.69 (0.69 to 1.65)	0.69 (0.69 to 0.99)	0.99 (0.69 to 3.08)
Week 20	0.69 (0.69 to 0.99)	0.69 (0.69 to 0.99)	0.99 (0.69 to 3.24)
Week 24	0.69 (0.69 to 0.99)	0.69 (0.69 to 0.99)	0.99 (0.69 to 3.09)
Week 28	0.69 (0.69 to 0.99)	0.69 (0.69 to 0.99)	0.99 (0.69 to 3.03)
Week 32	0.69 (0.69 to 0.99)	0.69 (0.69 to 0.99)	0.99 (0.69 to 2.87)
Week 36	0.69 (0.69 to 1.22)	0.69 (0.69 to 0.69)	0.99 (0.69 to 2.92)
Week 40	0.69 (0.69 to 1.89)	0.69 (0.69 to 0.69)	0.99 (0.69 to 2.65)
Week 44	0.69 (0.69 to 0.99)	0.69 (0.69 to 0.99)	0.99 (0.69 to 2.73)
Week 48	0.69 (0.69 to 1.83)	0.69 (0.69 to 0.69)	0.99 (0.69 to 2.70)
Week 50	0.69 (0.69 to 1.48)	1.02 (0.69 to 1.34)	0.99 (0.69 to 0.99)
Week 52	0.69 (0.69 to 1.75)	1.46 (1.04 to 1.88)	0.99 (0.69 to 0.99)
Week 54	0.69 (0.69 to 1.64)	2.08 (0.69 to 2.76)	0.99 (0.69 to 0.99)
Week 56	0.99 (0.69 to 4.07)	1.94 (0.69 to 3.44)	1.54 (0.69 to 6.09)
Week 58	0.69 (0.69 to 1.44)	1.75 (1.75 to 1.75)	0.99 (0.69 to 2.49)
Week 60	0.69 (0.69 to 1.89)	1.25 (0.69 to 1.82)	0.99 (0.69 to 2.65)
Week 64	0.99 (0.69 to 3.85)	1.28 (0.69 to 2.82)	0.99 (0.69 to 5.98)
Week 68	1.28 (0.99 to 1.56)	1.99 (1.99 to 1.99)	0.99 (0.99 to 1.10)
Week 72	0.99 (0.69 to 3.87)	1.77 (0.69 to 4.52)	1.08 (0.69 to 6.04)

Notes
[82] - Week 2,4,72:n=31 8,16,24,28,44,48,56:n=30 12,20,32,36:n=29 50: n=11 52: n=10 54,58,60,68: n<10
[83] - Weeks: 16,24,40,44,56,72: n=9 32,64: n=8 50,52,60: n=2 54: n=4 58,68: n=1
[84] - Weeks: 2,8-24,32: n=29 28, 36-48,56,64,71: n=28 50-54,58,60,68: n=5

No statistical analyses for this end point

Secondary: Part 3: HBV Core-Related Antigen (HBcrAg) Levels

Top of page

End point title

Part 3: HBV Core-Related Antigen (HBcrAg) Levels ^[85]

End point description

End point type

Secondary

End point timeframe

Baseline - Week 72

Notes
[85] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32 ^[86]	10 ^[87]	30 ^[88]
Units: Log10 U/mL
median (full range (min-max))
Baseline	4.10 (1.90 to 6.90)	6.15 (2.90 to 7.80)	7.95 (1.90 to 9.10)
Week 2	4.10 (1.90 to 6.80)	5.95 (1.90 to 7.60)	7.80 (1.90 to 9.00)
Week 4	4.20 (1.90 to 6.80)	5.55 (1.90 to 7.20)	7.00 (1.90 to 8.70)
Week 8	4.30 (1.90 to 6.80)	5.25 (1.90 to 6.50)	6.70 (1.90 to 8.90)
Week 12	4.30 (1.90 to 6.70)	5.15 (1.90 to 6.20)	6.30 (1.90 to 8.80)
Week 16	4.05 (1.90 to 6.60)	5.50 (2.90 to 6.00)	6.20 (2.50 to 8.70)
Week 20	4.10 (2.50 to 6.70)	5.00 (2.90 to 6.00)	5.90 (2.50 to 8.30)
Week 24	4.20 (2.90 to 6.60)	5.10 (2.50 to 5.90)	5.70 (1.90 to 8.00)
Week 28	4.05 (2.50 to 6.40)	5.00 (1.90 to 5.90)	5.60 (2.50 to 7.70)
Week 32	4.20 (2.50 to 6.50)	4.85 (2.90 to 6.10)	5.40 (1.90 to 9.10)
Week 36	4.05 (2.90 to 6.40)	5.10 (2.90 to 6.10)	5.45 (1.90 to 7.80)
Week 40	4.10 (2.90 to 6.50)	4.90 (2.50 to 6.10)	5.45 (2.50 to 7.50)
Week 44	4.35 (2.90 to 6.40)	4.80 (2.50 to 6.10)	5.35 (1.90 to 7.80)
Week 48	4.10 (2.50 to 6.60)	5.10 (2.90 to 6.00)	5.45 (2.50 to 9.10)
Week 50	4.00 (1.90 to 4.80)	5.05 (4.80 to 5.30)	3.10 (2.90 to 4.80)
Week 52	3.60 (1.90 to 4.90)	5.05 (4.90 to 5.20)	3.10 (2.90 to 4.80)
Week 54	3.30 (2.50 to 4.80)	3.90 (2.50 to 5.50)	3.10 (2.90 to 4.90)
Week 56	4.15 (2.50 to 6.50)	5.00 (2.90 to 6.10)	5.50 (1.90 to 9.10)
Week 58	2.50 (2.50 to 4.60)	5.30 (5.30 to 5.30)	3.20 (2.90 to 6.10)
Week 60	4.15 (2.50 to 4.70)	3.60 (2.50 to 4.70)	2.90 (2.50 to 6.50)
Week 64	4.20 (2.50 to 6.50)	4.40 (2.90 to 5.60)	5.15 (1.90 to 9.10)
Week 68	3.80 (2.90 to 4.70)	5.30 (5.30 to 5.40)	3.20 (3.00 to 4.40)
Week 72	4.20 (1.90 to 6.40)	4.80 (2.50 to 6.50)	4.70 (1.90 to 9.10)

Notes
[86] - Weeks: 2,4,72: n=31 8-20,28-48,56: n=30 24: n=29 50: n=11 52: n=10 54,58,60,68: n<10
[87] - Weeks: 16,24,40,44,56,72: n=9 32,64: n=8 50,52,60: n=2 54: n=4 58,68: n=1
[88] - Weeks: 2,8,16-32: n=29 36-48,56,65,72: n=28 50-54,58,60,68: n=5

No statistical analyses for this end point

Secondary: Part 3: Alanine Transaminase (ALT) Normalization in Participants with Baseline ALT Elevation

Top of page

End point title

Part 3: Alanine Transaminase (ALT) Normalization in Participants with Baseline ALT Elevation ^[89]

End point description

This endpoint includes participants from Part 3 with elevated ALT at baseline.

End point type

Secondary

End point timeframe

Week 12 - Week 72

Notes
[89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	0 ^[90]	9	28
Units: Percentage of participants
number (not applicable)
Week 12		66.67	35.71
Week 24		88.89	62.96
Week 36		88.89	77.78
Week 48		88.89	85.19
Week 56		77.78	81.48
Week 64		100	92.59
Week 72		87.5	92.59

Notes
[90] - Participants in Cohort A had normal ALT at baseline.

No statistical analyses for this end point

Secondary: Part 3: Anti-Hepatitis B Core Antigen (HBc) Antibodies

Top of page

End point title

Part 3: Anti-Hepatitis B Core Antigen (HBc) Antibodies ^[91]

End point description

End point type

Secondary

End point timeframe

Up to Week 72

Notes
[91] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32	10	30
Units: Percentage of participants	100	100	100

No statistical analyses for this end point

Secondary: Part 3: HBV DNA level

Top of page

End point title

Part 3: HBV DNA level ^[92]

End point description

End point type

Secondary

End point timeframe

Baseline - Week 72

Notes
[92] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32 ^[93]	10 ^[94]	30 ^[95]
Units: Log10 copies/mL
median (full range (min-max))
Baseline	1.28 (1.28 to 1.28)	6.06 (2.61 to 8.84)	7.37 (3.43 to 9.36)
Week 2	1.28 (1.28 to 1.28)	3.14 (1.28 to 6.47)	3.89 (0.95 to 6.40)
Week 4	1.28 (1.28 to 1.28)	1.99 (1.28 to 5.44)	2.76 (0.95 to 5.78)
Week 8	1.28 (1.28 to 1.28)	1.41 (1.28 to 3.73)	1.54 (0.95 to 6.15)
Week 12	1.28 (1.28 to 1.91)	1.28 (1.28 to 1.97)	1.44 (0.95 to 4.69)
Week 16	1.28 (1.28 to 1.41)	1.28 (1.28 to 2.33)	1.28 (0.95 to 3.99)
Week 20	1.28 (1.28 to 1.28)	1.28 (1.28 to 2.01)	1.28 (0.95 to 3.28)
Week 24	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.45)	1.28 (0.95 to 2.55)
Week 28	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.28)	1.28 (0.95 to 2.55)
Week 32	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.43)	1.28 (0.95 to 4.11)
Week 36	1.28 (1.28 to 1.32)	1.28 (1.28 to 1.41)	1.28 (0.95 to 2.21)
Week 40	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.62)	1.28 (0.95 to 2.08)
Week 44	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.28)	1.28 (0.95 to 2.39)
Week 48	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.28)	1.28 (0.95 to 2.10)
Week 50	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.28)	0.95 (0.95 to 1.28)
Week 52	1.28 (1.28 to 1.59)	1.28 (1.28 to 1.28)	1.28 (0.95 to 2.01)
Week 54	1.28 (1.28 to 1.30)	1.28 (1.28 to 1.28)	1.28 (0.95 to 2.89)
Week 56	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.53)	1.28 (0.95 to 5.02)
Week 58	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.28)	2.09 (0.95 to 4.88)
Week 60	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.28)	2.52 (0.95 to 5.23)
Week 64	1.28 (1.28 to 1.28)	1.28 (1.28 to 2.94)	1.28 (0.95 to 6.65)
Week 68	1.28 (1.28 to 1.28)	1.28 (1.28 to 1.28)	2.67 (0.95 to 4.66)
Week 72	1.28 (1.28 to 1.28)	1.28 (1.28 to 6.33)	1.28 (0.95 to 4.70)

Notes
[93] - Weeks: 2,4,64: n=31 8,16-24,32-48,56,72: n=30 12,28: n=29 50: n=11 52: n=10 54,58,60,68: n<10
[94] - Weeks: 16,24,40,44,56,,72: n=9 32: n=8 50,52,60: n=2 54: n=4 58,68: n=1
[95] - Weeks: 2,8,16-28: n=29 32-44,56,64,72: n=28 48: n=27 50--54,58,60,68: n=5

No statistical analyses for this end point

Secondary: Part 3: HBV DNA < Lower Limit of Quantification (LLOQ)

Top of page

End point title

Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) ^[96]

End point description

End point type

Secondary

End point timeframe

Baseline - Week 72

Notes
[96] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32 ^[97]	10 ^[98]	30 ^[99]
Units: Percentage of participants
number (not applicable)
Baseline	100	0	0
Week 2	100	10	10.3
Week 4	100	30	16.7
Week 8	100	40	41.4
Week 12	96.4	70	43.3
Week 16	96.7	77.8	51.7
Week 20	100	90	55.2
Week 24	100	88.9	51.7
Week 28	100	100	55.2
Week 32	100	87.5	64.3
Week 36	96.7	90	67.9
Week 40	100	77.8	71.4
Week 44	100	100	71.4
Week 48	100	100	81.5
Week 50	100	100	100
Week 52	90	100	80
Week 54	88.9	100	80
Week 56	100	88.9	64.3
Week 58	100	100	40
Week 60	100	100	20
Week 64	100	83.3	67.9
Week 68	100	100	40
Week 72	100	77.8	78.6

Notes
[97] - Weeks: 2,4,64: n=31 8,16-24,32-48,56,72: n=30 12: n=28 28: n=29 50: n=11 52: n=10 54,58,60,68: n<10
[98] - Weeks: 16,24,40,44,56,72: n=9 32: n=8 50,52,60: n=2 54: n=4 58,68: n=1
[99] - Weeks: 2,8,16-28: n=29 32-44,56,64,72: n=28 48: n=27 50-54,58,60,68: n=5

No statistical analyses for this end point

Secondary: Part 3: Tmax of RO7049389

Top of page

End point title

Part 3: Tmax of RO7049389 ^[100]

End point description

9999 = Data for the endpoint was not collected at the timepoint

End point type

Secondary

End point timeframe

Day 1 - Week 48

Notes
[100] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32 ^[101]	10 ^[102]	30 ^[103]
Units: Hours
median (full range (min-max))
Day 1	1.99 (0.98 to 3.03)	2.00 (1.00 to 3.02)	1.96 (0.95 to 3.02)
Week 4	9999 (9999 to 9999)	2.02 (1.00 to 3.02)	9999 (9999 to 9999)
Week 24	1.94 (0.00 to 3.00)	2.00 (1.00 to 3.00)	2.00 (0.92 to 4.15)
Week 48	1.02 (0.00 to 3.13)	2.50 (1.00 to 3.05)	2.00 (0.93 to 3.97)

Notes
[101] - Weeks 24, 28: n=30
[102] - Weeks 4, 24: n=9
[103] - Week 24: n=29 Week 48: n=28

No statistical analyses for this end point

Secondary: Part 3: Cmax of RO7049389

Top of page

End point title

Part 3: Cmax of RO7049389 ^[104]

End point description

9999 = Data for the endpoint was not collected at the timepoint

End point type

Secondary

End point timeframe

Day 1 - Week 48

Notes
[104] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32 ^[105]	10 ^[106]	30
Units: ng/mL
geometric mean (geometric coefficient of variation)
Day 1	7140 ( 107.6 )	5390 ( 94.3 )	5910 ( 116.8 )
Week 4	9999 ( 9999 )	4630 ( 92.8 )	9999 ( 9999 )
Week 24	2500 ( 2040.7 )	3900 ( 126.9 )	4260 ( 89.4 )
Week 48	5410 ( 88.4 )	3510 ( 246.1 )	3570 ( 133.6 )

Notes
[105] - Weeks 24, 28: n=30
[106] - Weeks 4, 24: n=9

No statistical analyses for this end point

Secondary: Part 3: AUCtau of RO7049389

Top of page

End point title

Part 3: AUCtau of RO7049389 ^[107]

End point description

9999 = Data for the endpoint was not collected at the timepoint

End point type

Secondary

End point timeframe

Day 1 - Week 48

Notes
[107] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32 ^[108]	10 ^[109]	30 ^[110]
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
Day 1	18700 ( 105.1 )	16700 ( 79.3 )	20900 ( 107.4 )
Week 4	9999 ( 9999 )	13600 ( 117.2 )	9999 ( 9999 )
Week 24	15400 ( 121.3 )	10500 ( 241.8 )	13200 ( 88.2 )
Week 48	14100 ( 84.8 )	16000 ( 121.3 )	11700 ( 107.6 )

Notes
[108] - Week 24: n=26 Weeks 48: n=28
[109] - Day 1; Weeks 24, 48: n=8 Week 4: n=9
[110] - Day 1: n=25 Week 24: n=23 Week 48: n=27

No statistical analyses for this end point

Secondary: Part 3: T1/2 of RO7049389

Top of page

End point title

Part 3: T1/2 of RO7049389 ^[111]

End point description

9999 = Data for the endpoint was not collected at the timepoint

End point type

Secondary

End point timeframe

Day 1 - Week 48

Notes
[111] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is specific to the reported arms.

End point values	Part 3: Cohort A	Part 3: Cohort B	Part 3: Cohort C
Number of subjects analysed	32 ^[112]	10 ^[113]	30 ^[114]
Units: Hours
median (full range (min-max))
Day 1	1.16 (0.757 to 1.67)	1.13 (0.891 to 1.31)	1.31 (0.899 to 1.98)
Week 4	9999 (9999 to 9999)	1.38 (0.897 to 1.89)	9999 (9999 to 9999)
Week 24	1.30 (0.832 to 2.19)	1.43 (1.17 to 2.38)	1.38 (1.06 to 2.25)
Week 48	4.05 (2.62 to 7.59)	3.40 (2.63 to 5.85)	3.98 (2.54 to 8.33)

Notes
[112] - Week 24: n=26 Week 48: n=27
[113] - Day 1; Weeks 24, 48: n=8
[114] - Day 1: n=25 Week 24: n=23 Week 48: n=27

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Up to Day 29 (Part 1a), Day 44 (Part 1b), Day 42 (Part 1c), Day 112 (Part 2), and 72 weeks (Part 3)

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

Part 3: Cohort B

Reporting group description

Reporting group title

Part 3: Cohort A

Reporting group description

Reporting group title

Parts 1a and 1b: Single ascending dose (SAD) Placebo

Reporting group description

Healthy volunteers (HVs) received a single dose of placebo under fasted (Part 1a) or fed (Part 1b) conditions.

Reporting group title

Part 3: Cohort C

Reporting group description

Reporting group title

Part 1a: SAD Cohort 3

Reporting group description

HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a: SAD Cohort 4

Reporting group description

HVs received a single dose of 2000 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a and 1b: SAD Cohort 2 (food effect)

Reporting group description

Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions. Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.

Reporting group title

Part 1a: SAD Cohort 1

Reporting group description

HVs received a single dose of 150 mg of RO7049389 under fasted conditions.

Reporting group title

Part 2: Proof-of-Mechanism (POM) Placebo

Reporting group description

Participants with chronic hepatitis B virus (CHB) infection received placebo once daily (QD) or twice daily (BID) for 27 days, followed by a single dose on Day 28.

Reporting group title

Part 1c: Multiple ascending dose (MAD) Placebo

Reporting group description

HVs received placebo either once-daily (QD) or twice-daily (BID) for 13 days, followed by a single dose on Day 14.

Reporting group title

Part 1a: SAD Cohort 5

Reporting group description

HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1a: SAD Cohort 6

Reporting group description

HVs received a single dose of 2500 mg of RO7049389 under fasted conditions.

Reporting group title

Part 1c: MAD Cohort 1

Reporting group description

HVs received 200 mg of RO7049389 BID under fasted conditions for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14.

Reporting group title

Part 1c: MAD Cohort 2

Reporting group description

Reporting group title

Part 1c: MAD Cohort 3

Reporting group description

Reporting group title

Part 1c: MAD Cohort 4

Reporting group description

Reporting group title

Part 1c: MAD Cohort 5

Reporting group description

Reporting group title

Part 2: POM Cohort 1

Reporting group description

Participants with CHB received 200 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 2

Reporting group description

Participants with CHB received 400 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 3

Reporting group description

Participants with CHB received 600 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 4

Reporting group description

Participants with CHB received 1000 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Reporting group title

Part 2: POM Cohort 5

Reporting group description

Participants with CHB received 200 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28.

Part 3: Cohort B

Part 3: Cohort A

Parts 1a and 1b: Single ascending dose (SAD) Placebo

Part 3: Cohort C

Part 1a: SAD Cohort 3

Part 1a: SAD Cohort 4

Part 1a and 1b: SAD Cohort 2 (food effect)

Part 1a: SAD Cohort 1

Part 2: Proof-of-Mechanism (POM) Placebo

Part 1c: Multiple ascending dose (MAD) Placebo

Part 1a: SAD Cohort 5

Part 1a: SAD Cohort 6

Part 1c: MAD Cohort 1

Part 1c: MAD Cohort 2

Part 1c: MAD Cohort 3

Part 1c: MAD Cohort 4

Part 1c: MAD Cohort 5

Part 2: POM Cohort 1

Part 2: POM Cohort 2

Part 2: POM Cohort 3

Part 2: POM Cohort 4

Part 2: POM Cohort 5

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 10 (10.00%)

1 / 32 (3.13%)

0 / 11 (0.00%)

2 / 30 (6.67%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

Investigations

Liver function test increased

subjects affected / exposed

0 / 10 (0.00%)

0 / 32 (0.00%)

0 / 11 (0.00%)

0 / 30 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant melanoma

subjects affected / exposed

1 / 10 (10.00%)

0 / 32 (0.00%)

0 / 11 (0.00%)

0 / 30 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

Nervous system disorders

Dizziness

subjects affected / exposed

0 / 10 (0.00%)

0 / 32 (0.00%)

0 / 11 (0.00%)

1 / 30 (3.33%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Lymphadenitis

subjects affected / exposed

1 / 10 (10.00%)

0 / 32 (0.00%)

0 / 11 (0.00%)

0 / 30 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

Hypersensitivity

subjects affected / exposed

0 / 10 (0.00%)

0 / 32 (0.00%)

0 / 11 (0.00%)

1 / 30 (3.33%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Gastrooesophageal reflux disease

subjects affected / exposed

0 / 10 (0.00%)

1 / 32 (3.13%)

0 / 11 (0.00%)

0 / 30 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Cellulitis

subjects affected / exposed

1 / 10 (10.00%)

0 / 32 (0.00%)

0 / 11 (0.00%)

1 / 30 (3.33%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper respiratory tract infection

subjects affected / exposed

0 / 10 (0.00%)

0 / 32 (0.00%)

0 / 11 (0.00%)

1 / 30 (3.33%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part 3: Cohort B	Part 3: Cohort A	Parts 1a and 1b: Single ascending dose (SAD) Placebo	Part 3: Cohort C	Part 1a: SAD Cohort 3	Part 1a: SAD Cohort 4	Part 1a and 1b: SAD Cohort 2 (food effect)	Part 1a: SAD Cohort 1	Part 2: Proof-of-Mechanism (POM) Placebo	Part 1c: Multiple ascending dose (MAD) Placebo	Part 1a: SAD Cohort 5	Part 1a: SAD Cohort 6	Part 1c: MAD Cohort 1	Part 1c: MAD Cohort 2	Part 1c: MAD Cohort 3	Part 1c: MAD Cohort 4	Part 1c: MAD Cohort 5	Part 2: POM Cohort 1	Part 2: POM Cohort 2	Part 2: POM Cohort 3	Part 2: POM Cohort 4	Part 2: POM Cohort 5
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 10 (90.00%)	22 / 32 (68.75%)	3 / 11 (27.27%)	30 / 30 (100.00%)	3 / 3 (100.00%)	5 / 6 (83.33%)	3 / 6 (50.00%)	1 / 3 (33.33%)	3 / 6 (50.00%)	6 / 10 (60.00%)	2 / 6 (33.33%)	3 / 6 (50.00%)	5 / 6 (83.33%)	4 / 7 (57.14%)	2 / 7 (28.57%)	1 / 6 (16.67%)	1 / 6 (16.67%)	4 / 6 (66.67%)	4 / 6 (66.67%)	5 / 6 (83.33%)	4 / 7 (57.14%)	2 / 6 (33.33%)
General disorders and administration site conditions
Catheter site bruise
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Catheter site erythema
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Catheter site pain
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Catheter site swelling
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Chest discomfort
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	4 / 30 (13.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	6	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Fatigue
subjects affected / exposed	1 / 10 (10.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	9 / 30 (30.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	13	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Influenza like illness
subjects affected / exposed	0 / 10 (0.00%)	5 / 32 (15.63%)	0 / 11 (0.00%)	5 / 30 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	7	0	9	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0	0
Injection site erythema
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	4 / 30 (13.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	4 / 30 (13.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	6	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Medical device site dermatitis
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Medical device site rash
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pain
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	18 / 30 (60.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	35	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Swelling face
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Vessel puncture site haematoma
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Reproductive system and breast disorders
Heavy menstrual bleeding
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Menstrual disorder
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Intermenstrual bleeding
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 10 (0.00%)	2 / 32 (6.25%)	0 / 11 (0.00%)	4 / 30 (13.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	4	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Dry throat
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Dysphonia
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	1 / 10 (10.00%)	2 / 32 (6.25%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)
occurrences all number	2	3	0	2	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	2	0
Rhinitis allergic
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Rhinorrhoea
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 10 (10.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	11 / 30 (36.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 7 (14.29%)	2 / 6 (33.33%)
occurrences all number	1	1	0	13	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	2	2
Aspartate aminotransferase increased
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	9 / 30 (30.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 6 (16.67%)
occurrences all number	0	1	0	12	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	2	1
Blood triglycerides increased
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	4 / 30 (13.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	6	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	6 / 30 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	12	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	12 / 30 (40.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	17	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	7 / 30 (23.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	7	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
White blood cell count decreased
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	7 / 30 (23.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	11	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Dental restoration failure
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle strain
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Thermal burn
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Tooth fracture
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac disorders
Palpitations
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	5	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	6 / 30 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)
occurrences all number	0	1	0	10	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	2	0
Hypoaesthesia
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	1	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Headache
subjects affected / exposed	2 / 10 (20.00%)	3 / 32 (9.38%)	2 / 11 (18.18%)	14 / 30 (46.67%)	1 / 3 (33.33%)	4 / 6 (66.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 10 (20.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 7 (28.57%)	0 / 6 (0.00%)
occurrences all number	3	7	3	20	1	4	0	0	1	3	0	2	1	1	1	0	0	2	0	1	3	0
Lethargy
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lumbosacral radiculopathy
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Presyncope
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Iron deficiency anaemia
subjects affected / exposed	1 / 10 (10.00%)	2 / 32 (6.25%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Splenomegaly
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lymphadenitis
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ear and labyrinth disorders
Deafness
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Motion sickness
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eye disorders
Blepharitis
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blepharospasm
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctival haemorrhage
subjects affected / exposed	1 / 10 (10.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivitis allergic
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Orbital oedema
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Visual impairment
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Abdominal distension
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	4 / 30 (13.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Abdominal pain
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	4	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0
Abdominal pain upper
subjects affected / exposed	1 / 10 (10.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Constipation
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dental caries
subjects affected / exposed	0 / 10 (0.00%)	2 / 32 (6.25%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Diarrhoea
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	2	3	0
Dry mouth
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Dyspepsia
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Epigastric discomfort
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Flatulence
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Gastritis
subjects affected / exposed	1 / 10 (10.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	2 / 10 (20.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gingival bleeding
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Mouth ulceration
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 10 (10.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	5 / 30 (16.67%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	0 / 6 (0.00%)
occurrences all number	1	3	0	5	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Toothache
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Vomiting
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hepatobiliary disorders
Hepatic steatosis
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hepatitis
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	5 / 30 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	5	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Blister
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Alopecia
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	11 / 30 (36.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	11	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	1 / 11 (9.09%)	0 / 30 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Dermatitis allergic
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Eczema
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Dry skin
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Night sweats
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Petechiae
subjects affected / exposed	0 / 10 (0.00%)	2 / 32 (6.25%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pruritus
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	8 / 30 (26.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	9	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	7 / 30 (23.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	9	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0
Rash vesicular
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Endocrine disorders
Thyroid disorder
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Thyroid mass
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	3 / 30 (10.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	1	0	6	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	1	0
Back pain
subjects affected / exposed	2 / 10 (20.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	5 / 30 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	1	0	9	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Joint swelling
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Limb discomfort
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
Muscular weakness
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Myalgia
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	7 / 30 (23.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 6 (0.00%)
occurrences all number	0	0	0	11	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Neck pain
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	0 / 10 (0.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	3 / 30 (10.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infections and infestations
COVID-19
subjects affected / exposed	1 / 10 (10.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	1 / 10 (10.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	1 / 30 (3.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Mumps
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Nasopharyngitis
subjects affected / exposed	2 / 10 (20.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Periorbital cellulitis
subjects affected / exposed	1 / 10 (10.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 10 (0.00%)	3 / 32 (9.38%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 10 (0.00%)	5 / 32 (15.63%)	0 / 11 (0.00%)	5 / 30 (16.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 10 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	6	0	5	0	0	1	0	1	0	1	2	1	0	0	0	0	3	1	1	0	0
Urinary tract infection
subjects affected / exposed	1 / 10 (10.00%)	3 / 32 (9.38%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	6	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Viral infection
subjects affected / exposed	1 / 10 (10.00%)	1 / 32 (3.13%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vaginal infection
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Hyperlipidaemia
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	6 / 30 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	10	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Decreased appetite
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	10 / 30 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	12	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	3 / 30 (10.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hypocalcaemia
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	2 / 30 (6.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Increased appetite
subjects affected / exposed	0 / 10 (0.00%)	0 / 32 (0.00%)	0 / 11 (0.00%)	0 / 30 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

16 Aug 2017

Additional visits added to study schedule; clarification of the number of MAD cohorts

02 Jan 2019

Addition of study Part 3; update to study title

21 Jun 2019

Updated for participants in Part 3 to continue post-study NUC therapy; increase in overall sample size

21 May 2020

Updates to eligibility criteria

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Part 1: Percentage of Participants With Adverse Events

Primary: Part 1: Percentage of Participants With Adverse Events

Primary: Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389

Primary: Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389

Primary: Part 2: Percentage of Participants With Adverse Events

Primary: Part 2: Percentage of Participants With Adverse Events

Primary: Part 2: Quantitative Plasma HBV DNA Level

Primary: Part 2: Quantitative Plasma HBV DNA Level

Primary: Part 3: Proportion of patients achieving functional cure

Primary: Part 3: Proportion of patients achieving functional cure

Secondary: Part 1b: Food effect on Cmax of RO7049389

Secondary: Part 1b: Food effect on Cmax of RO7049389

Secondary: Part 1b: Food effect on AUCinf of RO7049389

Secondary: Part 1b: Food effect on AUCinf of RO7049389

Secondary: Part 1c: Cmax of Midazolam

Secondary: Part 1c: Cmax of Midazolam

Secondary: Part 1c: AUCinf of Midazolam

Secondary: Part 1c: AUCinf of Midazolam

Secondary: Part 1c: Tmax of RO7049389

Secondary: Part 1c: Tmax of RO7049389

Secondary: Part 1c: Cmax of RO7049389

Secondary: Part 1c: Cmax of RO7049389

Secondary: Part 1c: AUC0-12hr of RO7049389

Secondary: Part 1c: AUC0-12hr of RO7049389

Secondary: Part 1c: CLr of RO7049389

Secondary: Part 1c: CLr of RO7049389

Secondary: Part 1c: Accumulation Ratio of RO7049389

Secondary: Part 1c: Accumulation Ratio of RO7049389

Secondary: Part 1c: T1/2 of RO7049389

Secondary: Part 1c: T1/2 of RO7049389

Secondary: Part 1c: Ae of RO7049389

Secondary: Part 1c: Ae of RO7049389

Secondary: Part 1c: Ctrough of RO7049389

Secondary: Part 1c: Ctrough of RO7049389

Secondary: Part 2: HBV DNA < Lower Limit of Quantification (LLOQ)

Secondary: Part 2: HBV DNA < Lower Limit of Quantification (LLOQ)

Secondary: Part 2: Tmax of RO7049389

Secondary: Part 2: Tmax of RO7049389

Secondary: Part 2: Cmax of RO7049389

Secondary: Part 2: Cmax of RO7049389

Secondary: Part 2: AUCtau of RO7049389

Secondary: Part 2: AUCtau of RO7049389

Secondary: Part 2: Accumulation Ratio of RO7049389

Secondary: Part 2: Accumulation Ratio of RO7049389

Secondary: Part 2: T1/2 of RO7049389

Secondary: Part 2: T1/2 of RO7049389

Secondary: Part 2: Ctrough of RO7049389

Secondary: Part 2: Ctrough of RO7049389

Secondary: Part 3: Percentage of Participants with AEs

Secondary: Part 3: Percentage of Participants with AEs

Secondary: Part 3: Hepatitis B Surface Antigen (HBsAg) Level

Secondary: Part 3: Hepatitis B Surface Antigen (HBsAg) Level

Secondary: Part 3: Hepatitis B e-Antigen (HBeAg) Levels

Secondary: Part 3: Hepatitis B e-Antigen (HBeAg) Levels

Secondary: Part 3: HBV RNA level

Secondary: Part 3: HBV RNA level

Secondary: Part 3: HBV Core-Related Antigen (HBcrAg) Levels