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Clinical Trial Results:
A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-3682 with Either MK-8742 or MK-8408 in Subjects with Chronic HCV GT1 and GT2 Infection

Summary
EudraCT number	2014-003304-73
Trial protocol	SE ES DE DK LT AT PL GB IT
Global end of trial date	12 Dec 2016

Results information
Results version number	v1(current)
This version publication date	14 Dec 2017
First version publication date	14 Dec 2017
Other versions

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

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Trial information

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Sponsor protocol code

3682-011

ISRCTN number

US NCT number

NCT02332707

WHO universal trial number (UTN)

Other trial identifiers

MK-3682-011: Merck Protocol Number

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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

12 Dec 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Dec 2016

Was the trial ended prematurely?

Main objective of the trial

This is a randomized, three-part, open-label trial of grazoprevir (GZR; MK-5172) (100 mg) and uprifosbuvir (UPR; MK-3682) (300 mg or 450 mg), with either elbasvir (EBR; MK-8742) (50 mg) or ruzasvir (RZR; MK-8408) (60 mg), and with or without ribavirin (RBV), in treatment-naïve (TN) cirrhotic (C) or non-cirrhotic (NC) hepatitis C virus (HCV) participants with chronic HCV genotype (GT) 1 or GT2 infection. Part A will consist of 8 arms to evaluate the safety of dose combinations. In Part B, participants will take 2 GZR+UPR+RZR fixed dose combination (FDC) tablets once daily (q.d.) by mouth, with or without twice-daily (b.i.d.) RBV (200 mg capsules; weight-based dosing). Participants who relapse following completion of therapy in Part A will be offered the option of retreatment with 16 weeks of UPR+GZR+RZR with RBV in Part C (data obtained from Part C will not be used in the analysis of outcome measures).

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

22 Jan 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 18

Country: Number of subjects enrolled

Austria: 8

Country: Number of subjects enrolled

Canada: 31

Country: Number of subjects enrolled

Denmark: 26

Country: Number of subjects enrolled

France: 16

Country: Number of subjects enrolled

Germany: 12

Country: Number of subjects enrolled

Israel: 39

Country: Number of subjects enrolled

Italy: 12

Country: Number of subjects enrolled

Lithuania: 16

Country: Number of subjects enrolled

New Zealand: 9

Country: Number of subjects enrolled

Poland: 17

Country: Number of subjects enrolled

Spain: 63

Country: Number of subjects enrolled

Sweden: 15

Country: Number of subjects enrolled

United Kingdom: 8

Country: Number of subjects enrolled

United States: 152

Worldwide total number of subjects

442

EEA total number of subjects

193

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)

373

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This trial was conducted at 95 study sites in Asia, the European Union, and North America.

Screening details

The "Number Started" row reflects the number of randomized participants who received study treatment. A total of 443 participants were randomized but 1 participant withdrew consent prior to receiving any study treatment.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

A1: GT1 NC GZR+UPR+EBR (8 weeks)

Arm description

In Part A, HCV genotype GT1-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir

Investigational medicinal product code

Other name

MK-5172

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One GZR 100 mg tablet taken q.d.by mouth.

Investigational medicinal product name

Uprifosbuvir

Investigational medicinal product code

Other name

MK-3682

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two or 3 UPR 150 mg (300 mg or 450 mg total daily dose) tablets taken q.d. by mouth.

Investigational medicinal product name

Elbasvir

Investigational medicinal product code

Other name

MK-8742

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One EBR 50 mg tablet taken q.d. by mouth.

A2: GT1 NC GZR+UPR+RZR (8 weeks)

Arm description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir

Investigational medicinal product code

Other name

MK-5172

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One GZR 100 mg tablet taken q.d.by mouth.

Investigational medicinal product name

Uprifosbuvir

Investigational medicinal product code

Other name

MK-3682

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two or 3 UPR 150 mg (300 mg or 450 mg total daily dose) tablets taken q.d. by mouth.

Investigational medicinal product name

Ruzasvir

Investigational medicinal product code

Other name

MK-8408

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Six RZR 10 mg (60 mg total daily dose) capsules taken q.d. by mouth.

A3: GT2 NC GZR+UPR+EBR (8 weeks)

Arm description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir

Investigational medicinal product code

Other name

MK-5172

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One GZR 100 mg tablet taken q.d.by mouth.

Investigational medicinal product name

Uprifosbuvir

Investigational medicinal product code

Other name

MK-3682

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two or 3 UPR 150 mg (300 mg or 450 mg total daily dose) tablets taken q.d. by mouth.

Investigational medicinal product name

Elbasvir

Investigational medicinal product code

Other name

MK-8742

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One EBR 50 mg tablet taken q.d. by mouth.

A4: GT2 NC GZR+UPR+RZR (8 weeks)

Arm description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir

Investigational medicinal product code

Other name

MK-5172

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One GZR 100 mg tablet taken q.d.by mouth.

Investigational medicinal product name

Uprifosbuvir

Investigational medicinal product code

Other name

MK-3682

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two or 3 UPR 150 mg (300 mg or 450 mg total daily dose) tablets taken q.d. by mouth.

Investigational medicinal product name

Ruzasvir

Investigational medicinal product code

Other name

MK-8408

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Six RZR 10 mg (60 mg total daily dose) capsules taken q.d. by mouth.

A5: GT1 NC GZR+UPR+EBR (8 weeks)

Arm description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir

Investigational medicinal product code

Other name

MK-5172

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One GZR 100 mg tablet taken q.d.by mouth.

Investigational medicinal product name

Uprifosbuvir

Investigational medicinal product code

Other name

MK-3682

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two or 3 UPR 150 mg (300 mg or 450 mg total daily dose) tablets taken q.d. by mouth.

Investigational medicinal product name

Elbasvir

Investigational medicinal product code

Other name

MK-8742

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One EBR 50 mg tablet taken q.d. by mouth.

A6: GT1 NC GZR+UPR+RZR (8 weeks)

Arm description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir

Investigational medicinal product code

Other name

MK-5172

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One GZR 100 mg tablet taken q.d.by mouth.

Investigational medicinal product name

Uprifosbuvir

Investigational medicinal product code

Other name

MK-3682

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two or 3 UPR 150 mg (300 mg or 450 mg total daily dose) tablets taken q.d. by mouth.

Investigational medicinal product name

Ruzasvir

Investigational medicinal product code

Other name

MK-8408

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Six RZR 10 mg (60 mg total daily dose) capsules taken q.d. by mouth.

A7: GT2 NC GZR+UPR+EBR (8 weeks)

Arm description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir

Investigational medicinal product code

Other name

MK-5172

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One GZR 100 mg tablet taken q.d.by mouth.

Investigational medicinal product name

Uprifosbuvir

Investigational medicinal product code

Other name

MK-3682

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two or 3 UPR 150 mg (300 mg or 450 mg total daily dose) tablets taken q.d. by mouth.

Investigational medicinal product name

Elbasvir

Investigational medicinal product code

Other name

MK-8742

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One EBR 50 mg tablet taken q.d. by mouth.

A8: GT2 NC GZR+UPR+RZR (8 weeks)

Arm description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir

Investigational medicinal product code

Other name

MK-5172

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

One GZR 100 mg tablet taken q.d.by mouth.

Investigational medicinal product name

Uprifosbuvir

Investigational medicinal product code

Other name

MK-3682

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two or 3 UPR 150 mg (300 mg or 450 mg total daily dose) tablets taken q.d. by mouth.

Investigational medicinal product name

Ruzasvir

Investigational medicinal product code

Other name

MK-8408

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Six RZR 10 mg (60 mg total daily dose) capsules taken q.d. by mouth.

B9: GT1 NC GZR+UPR+RZR (12 weeks)

Arm description

In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV

Arm description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. Participants also took RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight.

Arm type

Experimental

Investigational medicinal product name

Ribavirin

Investigational medicinal product code

Other name

Rebetol®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

RBV 200 mg capsules taken b.i.d. at a total daily dose of 800-1400 mg based on participant body weight.

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

B11: GT2 NC GZR+UPR+RZR (12 weeks)

Arm description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

B12: GT1 C GZR+UPR+RZR (8 weeks)

Arm description

In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

B13: GT1 C GZR+UPR+RZR (12 weeks)

Arm description

In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

B14: GT2 C GZR+UPR+RZR (12 weeks)

Arm description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV

Arm description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. Participants also took RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight.

Arm type

Experimental

Investigational medicinal product name

Ribavirin

Investigational medicinal product code

Other name

Rebetol®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

RBV 200 mg capsules taken b.i.d. at a total daily dose of 800-1400 mg based on participant body weight.

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

B16: GT2 C GZR+UPR+RZR (16 weeks)

Arm description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

B6: GT1 NC GZR+UPR+RZR (8 weeks)

Arm description

In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

B8: GT2 NC GZR+UPR+RZR (8 weeks)

Arm description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Arm type

Experimental

Investigational medicinal product name

Grazoprevir (+) Uprifosbuvir (+) Ruzasvir FDC

Investigational medicinal product code

Other name

MK-3682B

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg, taken q.d. by mouth.

Number of subjects in period 1	A1: GT1 NC GZR+UPR+EBR (8 weeks)	A2: GT1 NC GZR+UPR+RZR (8 weeks)	A3: GT2 NC GZR+UPR+EBR (8 weeks)	A4: GT2 NC GZR+UPR+RZR (8 weeks)	A5: GT1 NC GZR+UPR+EBR (8 weeks)	A6: GT1 NC GZR+UPR+RZR (8 weeks)	A7: GT2 NC GZR+UPR+EBR (8 weeks)	A8: GT2 NC GZR+UPR+RZR (8 weeks)	B9: GT1 NC GZR+UPR+RZR (12 weeks)	B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV	B11: GT2 NC GZR+UPR+RZR (12 weeks)	B12: GT1 C GZR+UPR+RZR (8 weeks)	B13: GT1 C GZR+UPR+RZR (12 weeks)	B14: GT2 C GZR+UPR+RZR (12 weeks)	B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV	B16: GT2 C GZR+UPR+RZR (16 weeks)	B6: GT1 NC GZR+UPR+RZR (8 weeks)	B8: GT2 NC GZR+UPR+RZR (8 weeks)
Started	23	24	16	14	23	23	15	16	48	31	31	35	40	15	16	26	30	16
Completed	23	24	15	13	23	22	15	16	48	28	29	35	35	15	16	26	30	16
Not completed	0	0	1	1	0	1	0	0	0	3	2	0	5	0	0	0	0	0
Consent withdrawn by subject	-	-	1	-	-	-	-	-	-	3	-	-	-	-	-	-	-	-
Physician decision	-	-	-	1	-	-	-	-	-	-	-	-	1	-	-	-	-	-
Adverse event, non-fatal	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-
Lost to follow-up	-	-	-	-	-	1	-	-	-	-	2	-	3	-	-	-	-	-

Baseline characteristics

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Reporting group title

A1: GT1 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV genotype GT1-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A2: GT1 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A3: GT2 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A4: GT2 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A5: GT1 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A6: GT1 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A7: GT2 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A8: GT2 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

B9: GT1 NC GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV

Reporting group description

Reporting group title

B11: GT2 NC GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B12: GT1 C GZR+UPR+RZR (8 weeks)

Reporting group description

In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Reporting group title

B13: GT1 C GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B14: GT2 C GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV

Reporting group description

Reporting group title

B16: GT2 C GZR+UPR+RZR (16 weeks)

Reporting group description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.

Reporting group title

B6: GT1 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Reporting group title

B8: GT2 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Reporting group values	A1: GT1 NC GZR+UPR+EBR (8 weeks)	A2: GT1 NC GZR+UPR+RZR (8 weeks)	A3: GT2 NC GZR+UPR+EBR (8 weeks)	A4: GT2 NC GZR+UPR+RZR (8 weeks)	A5: GT1 NC GZR+UPR+EBR (8 weeks)	A6: GT1 NC GZR+UPR+RZR (8 weeks)	A7: GT2 NC GZR+UPR+EBR (8 weeks)	A8: GT2 NC GZR+UPR+RZR (8 weeks)	B9: GT1 NC GZR+UPR+RZR (12 weeks)	B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV	B11: GT2 NC GZR+UPR+RZR (12 weeks)	B12: GT1 C GZR+UPR+RZR (8 weeks)	B13: GT1 C GZR+UPR+RZR (12 weeks)	B14: GT2 C GZR+UPR+RZR (12 weeks)	B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV	B16: GT2 C GZR+UPR+RZR (16 weeks)	B6: GT1 NC GZR+UPR+RZR (8 weeks)	B8: GT2 NC GZR+UPR+RZR (8 weeks)	Total
Number of subjects	23	24	16	14	23	23	15	16	48	31	31	35	40	15	16	26	30	16	442
Age categorical
Units: Subjects
Age Continuous
Units: Years
arithmetic mean (standard deviation)	50.2 ( 13.5 )	45.0 ( 14.5 )	49.4 ( 15.8 )	52.6 ( 11.6 )	49.0 ( 11.2 )	46.7 ( 13.9 )	52.9 ( 12.1 )	48.3 ( 8.8 )	48.8 ( 13.9 )	49.8 ( 13.0 )	55.6 ( 14.4 )	58.8 ( 9.6 )	56.9 ( 11.1 )	61.8 ( 6.8 )	59.8 ( 8.0 )	64.0 ( 9.3 )	47.4 ( 11.7 )	51.4 ( 10.8 )	-
Gender, Male/Female
Units: Subjects
Female	10	13	7	5	14	9	9	8	21	16	16	14	11	3	4	9	14	9	192
Male	13	11	9	9	9	14	6	8	27	15	15	21	29	12	12	17	16	7	250

End points

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Reporting group title

A1: GT1 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV genotype GT1-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A2: GT1 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + ruzasvir (RZR) 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A3: GT2 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A4: GT2 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A5: GT1 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A6: GT1 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A7: GT2 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A8: GT2 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

B9: GT1 NC GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV

Reporting group description

Reporting group title

B11: GT2 NC GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B12: GT1 C GZR+UPR+RZR (8 weeks)

Reporting group description

In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Reporting group title

B13: GT1 C GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B14: GT2 C GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV

Reporting group description

Reporting group title

B16: GT2 C GZR+UPR+RZR (16 weeks)

Reporting group description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.

Reporting group title

B6: GT1 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Reporting group title

B8: GT2 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Primary: Percentage of participants achieving sustained virologic response 12 weeks after completing treatment (SVR12)

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End point title

Percentage of participants achieving sustained virologic response 12 weeks after completing treatment (SVR12) ^[1]

End point description

The percentage of participants with Hepatitis C virus (HCV) ribonucleic acid (RNA) < Lower Limit of Quantification (LLoQ) 12 weeks after completing treatment (i.e., SVR12) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL. The analysis population includes all randomized participants who received at least 1 dose of study drug and had SVR12 results available.

End point type

Primary

End point timeframe

Up to 28 weeks

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: Per protocol, only descriptive statistics are presented.

A1: GT1 NC GZR+UPR+EBR (8 weeks)

A2: GT1 NC GZR+UPR+RZR (8 weeks)

A3: GT2 NC GZR+UPR+EBR (8 weeks)

A4: GT2 NC GZR+UPR+RZR (8 weeks)

A5: GT1 NC GZR+UPR+EBR (8 weeks)

A6: GT1 NC GZR+UPR+RZR (8 weeks)

A7: GT2 NC GZR+UPR+EBR (8 weeks)

A8: GT2 NC GZR+UPR+RZR (8 weeks)

B9: GT1 NC GZR+UPR+RZR (12 weeks)

B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV

B11: GT2 NC GZR+UPR+RZR (12 weeks)

B12: GT1 C GZR+UPR+RZR (8 weeks)

B13: GT1 C GZR+UPR+RZR (12 weeks)

B14: GT2 C GZR+UPR+RZR (12 weeks)

B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV

B16: GT2 C GZR+UPR+RZR (16 weeks)

B6: GT1 NC GZR+UPR+RZR (8 weeks)

B8: GT2 NC GZR+UPR+RZR (8 weeks)

Number of subjects analysed

Units: Percentage of Participants

number (confidence interval 95%)

100.0 (85.2 to 100.0)

100.0 (85.8 to 100.0)

68.8 (41.3 to 89.0)

71.4 (41.9 to 91.6)

100.0 (85.2 to 100.0)

91.3 (72.0 to 98.9)

60.0 (32.3 to 83.7)

93.8 (69.8 to 99.8)

100.0 (92.6 to 100.0)

83.3 (65.3 to 94.4)

100.0 (88.4 to 100.0)

97.1 (85.1 to 99.9)

100.0 (91.0 to 100.0)

100.0 (78.2 to 100.0)

100.0 (79.4 to 100.0)

100.0 (86.3 to 100.0)

100.0 (88.4 to 100.0)

87.5 (61.7 to 98.4)

No statistical analyses for this end point

Primary: Percentage of participants experiencing an adverse event (AE)

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End point title

Percentage of participants experiencing an adverse event (AE) ^[2]

End point description

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. The analysis population includes all randomized participants who received at least 1 dose of study drug.

End point type

Primary

End point timeframe

Up to 18 weeks

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive statistics are presented.

End point values	A1: GT1 NC GZR+UPR+EBR (8 weeks)	A2: GT1 NC GZR+UPR+RZR (8 weeks)	A3: GT2 NC GZR+UPR+EBR (8 weeks)	A4: GT2 NC GZR+UPR+RZR (8 weeks)	A5: GT1 NC GZR+UPR+EBR (8 weeks)	A6: GT1 NC GZR+UPR+RZR (8 weeks)	A7: GT2 NC GZR+UPR+EBR (8 weeks)	A8: GT2 NC GZR+UPR+RZR (8 weeks)	B9: GT1 NC GZR+UPR+RZR (12 weeks)	B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV	B11: GT2 NC GZR+UPR+RZR (12 weeks)	B12: GT1 C GZR+UPR+RZR (8 weeks)	B13: GT1 C GZR+UPR+RZR (12 weeks)	B14: GT2 C GZR+UPR+RZR (12 weeks)	B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV	B16: GT2 C GZR+UPR+RZR (16 weeks)	B6: GT1 NC GZR+UPR+RZR (8 weeks)	B8: GT2 NC GZR+UPR+RZR (8 weeks)
Number of subjects analysed	23	24	16	14	23	23	15	16	48	31	31	35	40	15	16	26	30	16
Units: Percentage of Participants
number (not applicable)	60.9	83.3	56.3	71.4	73.9	60.9	62.3	86.7	68.8	72.9	80.6	71.0	57.1	72.5	53.3	81.3	69.2	75.0

No statistical analyses for this end point

Primary: Percentage of participants discontinuing from study treatment due to an AE

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End point title

Percentage of participants discontinuing from study treatment due to an AE ^[3]

End point description

End point type

Primary

End point timeframe

Up to 16 weeks

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Per protocol, only descriptive statistics are presented.

End point values	A1: GT1 NC GZR+UPR+EBR (8 weeks)	A2: GT1 NC GZR+UPR+RZR (8 weeks)	A3: GT2 NC GZR+UPR+EBR (8 weeks)	A4: GT2 NC GZR+UPR+RZR (8 weeks)	A5: GT1 NC GZR+UPR+EBR (8 weeks)	A6: GT1 NC GZR+UPR+RZR (8 weeks)	A7: GT2 NC GZR+UPR+EBR (8 weeks)	A8: GT2 NC GZR+UPR+RZR (8 weeks)	B9: GT1 NC GZR+UPR+RZR (12 weeks)	B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV	B11: GT2 NC GZR+UPR+RZR (12 weeks)	B12: GT1 C GZR+UPR+RZR (8 weeks)	B13: GT1 C GZR+UPR+RZR (12 weeks)	B14: GT2 C GZR+UPR+RZR (12 weeks)	B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV	B16: GT2 C GZR+UPR+RZR (16 weeks)	B6: GT1 NC GZR+UPR+RZR (8 weeks)	B8: GT2 NC GZR+UPR+RZR (8 weeks)
Number of subjects analysed	23	24	16	14	23	23	15	16	48	31	31	35	40	15	16	26	30	16
Units: Percentage of Participants
number (not applicable)	0	0	0	0	0	0	0	0	0	6.5	0	0	2.5	0	12.5	0	0	0

No statistical analyses for this end point

Secondary: Percentage of participants achieving Sustained Virologic Response 24 weeks after ending study treatment (SVR24)

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End point title

Percentage of participants achieving Sustained Virologic Response 24 weeks after ending study treatment (SVR24)

End point description

The percentage of participants with HCV RNA < LLoQ 24 weeks after completing treatment (i.e., SVR24) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL. The analysis population includes all randomized participants who received at least 1 dose of study drug and had SVR24 results available are included.

End point type

Secondary

End point timeframe

Up to 40 weeks

A1: GT1 NC GZR+UPR+EBR (8 weeks)

A2: GT1 NC GZR+UPR+RZR (8 weeks)

A3: GT2 NC GZR+UPR+EBR (8 weeks)

A4: GT2 NC GZR+UPR+RZR (8 weeks)

A5: GT1 NC GZR+UPR+EBR (8 weeks)

A6: GT1 NC GZR+UPR+RZR (8 weeks)

A7: GT2 NC GZR+UPR+EBR (8 weeks)

A8: GT2 NC GZR+UPR+RZR (8 weeks)

B9: GT1 NC GZR+UPR+RZR (12 weeks)

B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV

B11: GT2 NC GZR+UPR+RZR (12 weeks)

B12: GT1 C GZR+UPR+RZR (8 weeks)

B13: GT1 C GZR+UPR+RZR (12 weeks)

B14: GT2 C GZR+UPR+RZR (12 weeks)

B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV

B16: GT2 C GZR+UPR+RZR (16 weeks)

B6: GT1 NC GZR+UPR+RZR (8 weeks)

B8: GT2 NC GZR+UPR+RZR (8 weeks)

Number of subjects analysed

Units: Percentage of Participants

number (confidence interval 95%)

100.0 (85.2 to 100.0)

100.0 (85.8 to 100.0)

68.8 (41.3 to 89.0)

71.4 (41.9 to 91.6)

100.0 (85.2 to 100.0)

90.9 (70.8 to 98.9)

60.0 (32.3 to 83.7)

93.8 (69.8 to 99.8)

100.0 (92.6 to 100.0)

83.3 (65.3 to 94.4)

100.0 (88.1 to 100.0)

97.1 (85.1 to 99.9)

100.0 (90.1 to 100.0)

100.0 (78.2 to 100.0)

100.0 (79.4 to 100.0)

100.0 (86.3 to 100.0)

100.0 (88.4 to 100.0)

87.5 (61.7 to 98.4)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 18 weeks (14 days after completing all study therapy)

Adverse event reporting additional description

All participants who received at least 1 dose of study treatment are included.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.1

Reporting group title

A2: GT1 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A1: GT1 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A3: GT2 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A4: GT2 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A5: GT1 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

A6: GT1 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT1-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A8: GT2 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks.

Reporting group title

A7: GT2 NC GZR+UPR+EBR (8 weeks)

Reporting group description

In Part A, HCV GT2-infected NC participants took GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks.

Reporting group title

B6: GT1 NC GZR+UPR+RVR (8 weeks)

Reporting group description

In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Reporting group title

B8: GT2 NC GZR+UPR+RZR (8 weeks)

Reporting group description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Reporting group title

B9: GT1 NC GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT1-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV

Reporting group description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight.

Reporting group title

B11: GT2 NC GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT2-infected NC participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B12: GT1 C GZR+UPR+RZR (8 weeks)

Reporting group description

In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.

Reporting group title

B13: GT1 C GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT1-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B14: GT2 C GZR+UPR+RZR (12 weeks)

Reporting group description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks.

Reporting group title

B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV

Reporting group description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight.

Reporting group title

B16: GT2 C GZR+UPR+RZRasvir (16 weeks)

Reporting group description

In Part B, HCV GT2-infected C participants took 2 FDC tablets containing GZR 50 mg + UPR 225 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks.

A2: GT1 NC GZR+UPR+RZR (8 weeks)

A1: GT1 NC GZR+UPR+EBR (8 weeks)

A3: GT2 NC GZR+UPR+EBR (8 weeks)

A4: GT2 NC GZR+UPR+RZR (8 weeks)

A5: GT1 NC GZR+UPR+EBR (8 weeks)

A6: GT1 NC GZR+UPR+RZR (8 weeks)

A8: GT2 NC GZR+UPR+RZR (8 weeks)

A7: GT2 NC GZR+UPR+EBR (8 weeks)

B6: GT1 NC GZR+UPR+RVR (8 weeks)

B8: GT2 NC GZR+UPR+RZR (8 weeks)

B9: GT1 NC GZR+UPR+RZR (12 weeks)

B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV

B11: GT2 NC GZR+UPR+RZR (12 weeks)

B12: GT1 C GZR+UPR+RZR (8 weeks)

B13: GT1 C GZR+UPR+RZR (12 weeks)

B14: GT2 C GZR+UPR+RZR (12 weeks)

B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV

B16: GT2 C GZR+UPR+RZRasvir (16 weeks)

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 24 (4.17%)

0 / 23 (0.00%)

1 / 16 (6.25%)

1 / 14 (7.14%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

1 / 16 (6.25%)

0 / 48 (0.00%)

2 / 31 (6.45%)

0 / 31 (0.00%)

1 / 35 (2.86%)

3 / 40 (7.50%)

0 / 15 (0.00%)

0 / 16 (0.00%)

2 / 26 (7.69%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Squamous cell carcinoma

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

1 / 16 (6.25%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Atrial fibrillation

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

1 / 40 (2.50%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tachycardia

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 16 (6.25%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

Retinal artery occlusion

subjects affected / exposed

1 / 24 (4.17%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Duodenal ulcer haemorrhage

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

1 / 26 (3.85%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Oesophagitis

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

1 / 31 (3.23%)

0 / 31 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatitis

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

1 / 40 (2.50%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

1 / 16 (6.25%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Dyspnoea

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

1 / 40 (2.50%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Psychiatric disorders

Depression

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

1 / 31 (3.23%)

0 / 31 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Substance-induced psychotic disorder

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

1 / 14 (7.14%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Arthralgia

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

1 / 40 (2.50%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Infections and infestations

Device related infection

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

1 / 40 (2.50%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pilonidal cyst

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

1 / 35 (2.86%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

0 / 40 (0.00%)

0 / 15 (0.00%)

0 / 16 (0.00%)

1 / 26 (3.85%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Septic shock

subjects affected / exposed

0 / 24 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 14 (0.00%)

0 / 23 (0.00%)

0 / 16 (0.00%)

0 / 15 (0.00%)

0 / 30 (0.00%)

0 / 16 (0.00%)

0 / 48 (0.00%)

0 / 31 (0.00%)

0 / 35 (0.00%)

1 / 40 (2.50%)

0 / 15 (0.00%)

0 / 16 (0.00%)

0 / 26 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

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

Non-serious adverse events	A2: GT1 NC GZR+UPR+RZR (8 weeks)	A1: GT1 NC GZR+UPR+EBR (8 weeks)	A3: GT2 NC GZR+UPR+EBR (8 weeks)	A4: GT2 NC GZR+UPR+RZR (8 weeks)	A5: GT1 NC GZR+UPR+EBR (8 weeks)	A6: GT1 NC GZR+UPR+RZR (8 weeks)	A8: GT2 NC GZR+UPR+RZR (8 weeks)	A7: GT2 NC GZR+UPR+EBR (8 weeks)	B6: GT1 NC GZR+UPR+RVR (8 weeks)	B8: GT2 NC GZR+UPR+RZR (8 weeks)	B9: GT1 NC GZR+UPR+RZR (12 weeks)	B10: GT2 NC GZR+UPR+RZR (8 weeks) + RBV	B11: GT2 NC GZR+UPR+RZR (12 weeks)	B12: GT1 C GZR+UPR+RZR (8 weeks)	B13: GT1 C GZR+UPR+RZR (12 weeks)	B14: GT2 C GZR+UPR+RZR (12 weeks)	B15: GT2 C GZR+UPR+RZR (12 weeks) + RBV	B16: GT2 C GZR+UPR+RZRasvir (16 weeks)
Total subjects affected by non serious adverse events
subjects affected / exposed	19 / 24 (79.17%)	13 / 23 (56.52%)	10 / 16 (62.50%)	10 / 14 (71.43%)	15 / 23 (65.22%)	13 / 23 (56.52%)	12 / 16 (75.00%)	13 / 15 (86.67%)	18 / 30 (60.00%)	11 / 16 (68.75%)	35 / 48 (72.92%)	24 / 31 (77.42%)	19 / 31 (61.29%)	19 / 35 (54.29%)	26 / 40 (65.00%)	8 / 15 (53.33%)	13 / 16 (81.25%)	14 / 26 (53.85%)
Vascular disorders
Essential hypertension
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	1 / 30 (3.33%)	1 / 16 (6.25%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0
Hot flush
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	2 / 23 (8.70%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	2 / 48 (4.17%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	2	0	0	1	2	0	0	0	0	0	2	0	1	0	0	0	0	1
Hypertension
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	2 / 48 (4.17%)	0 / 31 (0.00%)	1 / 31 (3.23%)	3 / 35 (8.57%)	2 / 40 (5.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	2	0	1	3	2	0	0	1
Orthostatic hypotension
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)	3 / 16 (18.75%)	0 / 14 (0.00%)	2 / 23 (8.70%)	0 / 23 (0.00%)	1 / 16 (6.25%)	1 / 15 (6.67%)	0 / 30 (0.00%)	2 / 16 (12.50%)	0 / 48 (0.00%)	3 / 31 (9.68%)	1 / 31 (3.23%)	1 / 35 (2.86%)	0 / 40 (0.00%)	0 / 15 (0.00%)	3 / 16 (18.75%)	1 / 26 (3.85%)
occurrences all number	2	0	3	0	2	0	1	1	0	2	0	3	1	1	0	0	5	2
Chills
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	1 / 30 (3.33%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	2 / 31 (6.45%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	1	0	2	0	0	0	0	0
Crying
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Drug withdrawal syndrome
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Energy increased
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0
Fatigue
subjects affected / exposed	3 / 24 (12.50%)	4 / 23 (17.39%)	2 / 16 (12.50%)	2 / 14 (14.29%)	6 / 23 (26.09%)	4 / 23 (17.39%)	6 / 16 (37.50%)	6 / 15 (40.00%)	4 / 30 (13.33%)	3 / 16 (18.75%)	8 / 48 (16.67%)	4 / 31 (12.90%)	1 / 31 (3.23%)	3 / 35 (8.57%)	3 / 40 (7.50%)	1 / 15 (6.67%)	5 / 16 (31.25%)	3 / 26 (11.54%)
occurrences all number	3	5	2	2	6	4	6	6	4	4	9	4	1	3	3	1	5	4
Feeling cold
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Influenza like illness
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	1 / 16 (6.25%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	2 / 40 (5.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	1	0	0	0	0	0	0	1	0	1	1	0	0	0	2	0	0	1
Oedema peripheral
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Peripheral swelling
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0
Pyrexia
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	1	0	0	0	0	0
Vessel puncture site reaction
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Menstruation delayed
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Ovarian cyst
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	1 / 23 (4.35%)	1 / 23 (4.35%)	0 / 16 (0.00%)	1 / 15 (6.67%)	1 / 30 (3.33%)	0 / 16 (0.00%)	3 / 48 (6.25%)	4 / 31 (12.90%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	2 / 26 (7.69%)
occurrences all number	0	0	1	0	1	1	0	1	1	0	3	5	0	0	0	0	0	2
Dyspnoea
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	1 / 16 (6.25%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	1	0	0	0	1	1
Dyspnoea exertional
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	2 / 15 (13.33%)	1 / 30 (3.33%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	1 / 16 (6.25%)	1 / 26 (3.85%)
occurrences all number	0	0	1	0	0	0	0	3	1	0	0	1	0	0	0	1	1	1
Oropharyngeal pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	2 / 16 (12.50%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	2 / 48 (4.17%)	1 / 31 (3.23%)	1 / 31 (3.23%)	0 / 35 (0.00%)	2 / 40 (5.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	1	0	2	1	0	0	2	1	1	0	2	0	0	0
Respiratory tract congestion
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	2 / 31 (6.45%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	1 / 16 (6.25%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	1	0	1	1	0	0	0	0	0	0	0	0	1	0
Throat irritation
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Psychiatric disorders
Affective disorder
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Anxiety
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	2 / 48 (4.17%)	1 / 31 (3.23%)	2 / 31 (6.45%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	2	1	2	0	0	0	0	1
Depression
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	2 / 16 (12.50%)	2 / 15 (13.33%)	0 / 30 (0.00%)	0 / 16 (0.00%)	2 / 48 (4.17%)	2 / 31 (6.45%)	2 / 31 (6.45%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	1 / 26 (3.85%)
occurrences all number	1	0	0	0	0	0	2	3	0	0	2	3	2	0	0	0	1	1
Flat affect
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Initial insomnia
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Insomnia
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	2 / 14 (14.29%)	1 / 23 (4.35%)	0 / 23 (0.00%)	2 / 16 (12.50%)	2 / 15 (13.33%)	3 / 30 (10.00%)	1 / 16 (6.25%)	4 / 48 (8.33%)	4 / 31 (12.90%)	2 / 31 (6.45%)	0 / 35 (0.00%)	3 / 40 (7.50%)	0 / 15 (0.00%)	2 / 16 (12.50%)	1 / 26 (3.85%)
occurrences all number	1	0	0	2	1	0	2	3	3	1	5	4	2	0	3	0	2	1
Irritability
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	1 / 23 (4.35%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	2 / 16 (12.50%)	1 / 48 (2.08%)	2 / 31 (6.45%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	1	1	0	0	0	0	2	1	2	0	0	0	0	0	0
Libido decreased
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	1 / 30 (3.33%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Mood altered
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Sleep disorder
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	1 / 30 (3.33%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	1	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 24 (4.17%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	1 / 30 (3.33%)	1 / 16 (6.25%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	1	0	0	0	0	3	0	1	1	0	1	0	0	1	0	0	0
Blood potassium increased
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	1 / 30 (3.33%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	2 / 15 (13.33%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	2 / 16 (12.50%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	0	0	0	2	0	0	0	0	0	0	0	0	2	0
Heart rate decreased
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	1 / 16 (6.25%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Lipase increased
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1	0	1	0	0	1
Liver function test increased
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Pulse abnormal
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Weight increased
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	0	0	1	0	0	0	0	1	0	0
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)	1 / 15 (6.67%)	1 / 30 (3.33%)	0 / 16 (0.00%)	2 / 48 (4.17%)	2 / 31 (6.45%)	0 / 31 (0.00%)	1 / 35 (2.86%)	0 / 40 (0.00%)	1 / 15 (6.67%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	1	0	1	0	0	1	1	1	1	0	2	2	0	1	0	1	1	0
Contusion
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Sunburn
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	2 / 26 (7.69%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Palpitations
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 14 (0.00%)	2 / 23 (8.70%)	0 / 23 (0.00%)	1 / 16 (6.25%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	1 / 31 (3.23%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	2 / 16 (12.50%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0	3	0	1	1	0	0	0	1	2	0	0	0	3	0
Sinus bradycardia
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nervous system disorders
Disturbance in attention
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0
Dizziness
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 14 (0.00%)	4 / 23 (17.39%)	0 / 23 (0.00%)	0 / 16 (0.00%)	4 / 15 (26.67%)	1 / 30 (3.33%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	1 / 35 (2.86%)	1 / 40 (2.50%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0	5	0	0	5	1	0	4	0	0	1	1	0	1	0
Dysgeusia
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	2 / 23 (8.70%)	1 / 16 (6.25%)	0 / 15 (0.00%)	1 / 30 (3.33%)	0 / 16 (0.00%)	1 / 48 (2.08%)	2 / 31 (6.45%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	0	2	1	0	1	0	1	2	0	0	0	0	0	0
Headache
subjects affected / exposed	7 / 24 (29.17%)	3 / 23 (13.04%)	3 / 16 (18.75%)	2 / 14 (14.29%)	8 / 23 (34.78%)	3 / 23 (13.04%)	9 / 16 (56.25%)	5 / 15 (33.33%)	2 / 30 (6.67%)	3 / 16 (18.75%)	15 / 48 (31.25%)	8 / 31 (25.81%)	7 / 31 (22.58%)	5 / 35 (14.29%)	5 / 40 (12.50%)	2 / 15 (13.33%)	2 / 16 (12.50%)	4 / 26 (15.38%)
occurrences all number	9	5	4	2	9	4	10	5	2	3	25	8	7	6	11	2	2	10
Hypoaesthesia
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	1
Lethargy
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	2 / 14 (14.29%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	2	0	0	1	1	0	0	0	2	0	0	1	0	0	0
Paraesthesia
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	1 / 31 (3.23%)	0 / 31 (0.00%)	1 / 35 (2.86%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	1	1	0	1	0	0	0	0
Syncope
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0
Lymphadenopathy
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	3 / 30 (10.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	1 / 35 (2.86%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	4	0	1	0	0	1	0	0	0	0
Ear and labyrinth disorders
Excessive cerumen production
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tinnitus
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	1 / 31 (3.23%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	1	0	0	0	0	0
Vertigo
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	2 / 40 (5.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0	0	1	0	1	0	0	1	0	0	0	3	0	0	0
Eye disorders
Blepharospasm
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Vision blurred
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	1 / 16 (6.25%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	2 / 24 (8.33%)	2 / 23 (8.70%)	0 / 16 (0.00%)	1 / 14 (7.14%)	1 / 23 (4.35%)	1 / 23 (4.35%)	1 / 16 (6.25%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 31 (3.23%)	1 / 35 (2.86%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	1 / 26 (3.85%)
occurrences all number	2	2	0	1	1	1	1	1	0	0	0	0	1	1	0	0	1	1
Abdominal distension
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	1 / 16 (6.25%)	1 / 48 (2.08%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	1	0	0	0	1	0	0	0	0	1	1	0	1	0	1	0	0	1
Abdominal pain
subjects affected / exposed	1 / 24 (4.17%)	2 / 23 (8.70%)	2 / 16 (12.50%)	0 / 14 (0.00%)	0 / 23 (0.00%)	2 / 23 (8.70%)	1 / 16 (6.25%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	1 / 31 (3.23%)	0 / 31 (0.00%)	1 / 35 (2.86%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	3 / 26 (11.54%)
occurrences all number	1	2	2	0	0	2	1	1	0	0	1	1	0	1	1	0	0	3
Abdominal pain lower
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	1 / 35 (2.86%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	0	0	1	0	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	1 / 31 (3.23%)	2 / 35 (5.71%)	0 / 40 (0.00%)	1 / 15 (6.67%)	1 / 16 (6.25%)	4 / 26 (15.38%)
occurrences all number	0	0	0	1	0	1	1	0	0	0	0	1	1	2	0	1	1	4
Constipation
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	0 / 16 (0.00%)	2 / 15 (13.33%)	2 / 30 (6.67%)	2 / 16 (12.50%)	1 / 48 (2.08%)	2 / 31 (6.45%)	0 / 31 (0.00%)	1 / 35 (2.86%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	1	0	0	2	2	2	1	2	0	1	0	0	0	1
Diarrhoea
subjects affected / exposed	1 / 24 (4.17%)	1 / 23 (4.35%)	1 / 16 (6.25%)	0 / 14 (0.00%)	4 / 23 (17.39%)	1 / 23 (4.35%)	2 / 16 (12.50%)	0 / 15 (0.00%)	3 / 30 (10.00%)	1 / 16 (6.25%)	5 / 48 (10.42%)	4 / 31 (12.90%)	1 / 31 (3.23%)	1 / 35 (2.86%)	1 / 40 (2.50%)	2 / 15 (13.33%)	1 / 16 (6.25%)	1 / 26 (3.85%)
occurrences all number	1	1	1	0	4	1	2	0	3	1	5	4	1	1	1	2	1	1
Dry mouth
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)	0 / 15 (0.00%)	3 / 30 (10.00%)	0 / 16 (0.00%)	2 / 48 (4.17%)	1 / 31 (3.23%)	1 / 31 (3.23%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	2 / 26 (7.69%)
occurrences all number	2	0	0	0	0	1	1	0	3	0	2	1	1	0	1	0	0	2
Dyspepsia
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	3 / 15 (20.00%)	0 / 30 (0.00%)	1 / 16 (6.25%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	2	0	0	1	0	1	0	1	0
Epigastric discomfort
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	1 / 16 (6.25%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	1 / 35 (2.86%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Flatulence
subjects affected / exposed	2 / 24 (8.33%)	1 / 23 (4.35%)	1 / 16 (6.25%)	0 / 14 (0.00%)	2 / 23 (8.70%)	1 / 23 (4.35%)	2 / 16 (12.50%)	3 / 15 (20.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	3 / 48 (6.25%)	0 / 31 (0.00%)	2 / 31 (6.45%)	1 / 35 (2.86%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	2 / 26 (7.69%)
occurrences all number	2	2	1	0	3	1	2	3	0	0	3	0	2	1	1	0	0	3
Gastrointestinal disorder
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 16 (6.25%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	2 / 48 (4.17%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	2 / 40 (5.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	1	1	0	0	0	0	0	0	2	0	0	0	2	0	0	0
Gingival pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	1 / 16 (6.25%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	3 / 24 (12.50%)	2 / 23 (8.70%)	1 / 16 (6.25%)	2 / 14 (14.29%)	3 / 23 (13.04%)	0 / 23 (0.00%)	3 / 16 (18.75%)	6 / 15 (40.00%)	5 / 30 (16.67%)	2 / 16 (12.50%)	7 / 48 (14.58%)	5 / 31 (16.13%)	1 / 31 (3.23%)	1 / 35 (2.86%)	3 / 40 (7.50%)	2 / 15 (13.33%)	3 / 16 (18.75%)	4 / 26 (15.38%)
occurrences all number	3	2	1	3	3	0	3	8	5	3	7	6	1	1	3	2	3	4
Rectal haemorrhage
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Vomiting
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	2 / 30 (6.67%)	0 / 16 (0.00%)	2 / 48 (4.17%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	3 / 16 (18.75%)	2 / 26 (7.69%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	2	1	0	0	1	0	3	3
Hepatobiliary disorders
Hepatic pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	1 / 16 (6.25%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Dry skin
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	2 / 15 (13.33%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	3 / 31 (9.68%)	0 / 31 (0.00%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0	0	1	0	2	0	0	0	3	0	0	1	0	0	0
Erythema
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Hyperhidrosis
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	2 / 48 (4.17%)	0 / 31 (0.00%)	2 / 31 (6.45%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	2	0	2	0	0	0	0	0
Macule
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Pruritus
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	2 / 23 (8.70%)	0 / 16 (0.00%)	3 / 15 (20.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	5 / 31 (16.13%)	1 / 31 (3.23%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	1	0	1	0	0	2	0	3	0	0	1	5	1	0	1	0	1	0
Pruritus generalised
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	1 / 30 (3.33%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	1	0
Rash
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	1 / 23 (4.35%)	0 / 23 (0.00%)	1 / 16 (6.25%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	3 / 31 (9.68%)	0 / 31 (0.00%)	0 / 35 (0.00%)	1 / 40 (2.50%)	1 / 15 (6.67%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	3	0	0	1	2	0	1	1	0	0	1	5	0	0	1	2	0	1
Rash papular
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	1 / 15 (6.67%)	2 / 16 (12.50%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0
Vitiligo
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
Pollakiuria
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Renal pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Endocrine disorders
Androgen deficiency
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Hypothyroidism
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	3 / 23 (13.04%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 15 (0.00%)	2 / 30 (6.67%)	3 / 16 (18.75%)	1 / 48 (2.08%)	3 / 31 (9.68%)	1 / 31 (3.23%)	1 / 35 (2.86%)	3 / 40 (7.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	2 / 26 (7.69%)
occurrences all number	0	0	0	0	4	1	0	0	3	3	2	3	1	1	3	0	0	2
Back pain
subjects affected / exposed	2 / 24 (8.33%)	2 / 23 (8.70%)	3 / 16 (18.75%)	0 / 14 (0.00%)	1 / 23 (4.35%)	0 / 23 (0.00%)	2 / 16 (12.50%)	0 / 15 (0.00%)	1 / 30 (3.33%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	2	2	3	0	1	0	2	0	1	0	1	0	1	0	1	0	0	0
Bursitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	1 / 16 (6.25%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	2 / 40 (5.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	3	0	0	3	0	0	1
Muscular weakness
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	2 / 16 (12.50%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	1	0	0	0
Musculoskeletal stiffness
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Myalgia
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	3 / 15 (20.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	2 / 48 (4.17%)	1 / 31 (3.23%)	2 / 31 (6.45%)	1 / 35 (2.86%)	2 / 40 (5.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0	0	0	0	3	0	0	3	1	3	1	2	0	0	0
Pain in extremity
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	1 / 35 (2.86%)	0 / 40 (0.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	2
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	2 / 40 (5.00%)	1 / 15 (6.67%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1	0	0
Cystitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	2 / 35 (5.71%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	3	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0
Ear infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	2 / 31 (6.45%)	0 / 31 (0.00%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	1	0
Gingivitis
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	1 / 30 (3.33%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0
Influenza
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	3 / 48 (6.25%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	3	0	1	0	1	0	0	0
Nasopharyngitis
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	3 / 16 (18.75%)	3 / 15 (20.00%)	0 / 30 (0.00%)	1 / 16 (6.25%)	1 / 48 (2.08%)	3 / 31 (9.68%)	1 / 31 (3.23%)	1 / 35 (2.86%)	3 / 40 (7.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	2	0	1	0	0	0	3	4	0	1	1	3	1	1	4	0	0	2
Oral herpes
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	1 / 35 (2.86%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	2	0	0	1	0	0	1	0
Pneumonia
subjects affected / exposed	0 / 24 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Sialoadenitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Tooth abscess
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	1 / 30 (3.33%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	1 / 31 (3.23%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	2	0	0	0	1	0	1	0	0	0
Upper respiratory tract infection
subjects affected / exposed	2 / 24 (8.33%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 14 (7.14%)	0 / 23 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	0 / 15 (0.00%)	2 / 30 (6.67%)	2 / 16 (12.50%)	1 / 48 (2.08%)	1 / 31 (3.23%)	3 / 31 (9.68%)	0 / 35 (0.00%)	1 / 40 (2.50%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	2	0	0	1	0	1	0	0	3	2	1	1	3	0	1	0	2	0
Urinary tract infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	1 / 23 (4.35%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	1 / 31 (3.23%)	1 / 35 (2.86%)	1 / 40 (2.50%)	0 / 15 (0.00%)	1 / 16 (6.25%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	1	1	1	1	0	1	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 24 (4.17%)	0 / 23 (0.00%)	1 / 16 (6.25%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	1 / 15 (6.67%)	0 / 30 (0.00%)	0 / 16 (0.00%)	1 / 48 (2.08%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	0 / 26 (0.00%)
occurrences all number	1	0	1	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	0 / 31 (0.00%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	1 / 16 (6.25%)	0 / 26 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Increased appetite
subjects affected / exposed	0 / 24 (0.00%)	0 / 23 (0.00%)	0 / 16 (0.00%)	0 / 14 (0.00%)	0 / 23 (0.00%)	0 / 23 (0.00%)	2 / 16 (12.50%)	0 / 15 (0.00%)	0 / 30 (0.00%)	0 / 16 (0.00%)	0 / 48 (0.00%)	1 / 31 (3.23%)	0 / 31 (0.00%)	0 / 35 (0.00%)	0 / 40 (0.00%)	0 / 15 (0.00%)	0 / 16 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	1	0	0	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

15 Dec 2014

Amendment 01: The primary purpose of this amendment was to add additional doses and to increase treatment duration.

12 Jun 2015

Amendment 03: The primary purpose of this amendment was to add additional arms in a step-wise approach to limit the number of participants exposed to potentially suboptimal treatment regimens.

02 Nov 2015

Amendment 05: The primary purpose of this amendment was to update Part B based on interim results from Part A, and to also add cirrhotic participants.

09 Jun 2016

Amendment 07: The primary purpose of this amendment was to include enrolled participants with virologic failure on study to a follow-up study (MK-5172-017).

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

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Clinical trials

Clinical Trial Results:
A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-3682 with Either MK-8742 or MK-8408 in Subjects with Chronic HCV GT1 and GT2 Infection

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants achieving sustained virologic response 12 weeks after completing treatment (SVR12)

Primary: Percentage of participants achieving sustained virologic response 12 weeks after completing treatment (SVR12)

Primary: Percentage of participants experiencing an adverse event (AE)

Primary: Percentage of participants experiencing an adverse event (AE)

Primary: Percentage of participants discontinuing from study treatment due to an AE

Primary: Percentage of participants discontinuing from study treatment due to an AE

Secondary: Percentage of participants achieving Sustained Virologic Response 24 weeks after ending study treatment (SVR24)

Secondary: Percentage of participants achieving Sustained Virologic Response 24 weeks after ending study treatment (SVR24)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

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Estonia
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Ireland
Italy
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Clinical trials

Clinical Trial Results: A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-3682 with Either MK-8742 or MK-8408 in Subjects with Chronic HCV GT1 and GT2 Infection

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants achieving sustained virologic response 12 weeks after completing treatment (SVR12)

Primary: Percentage of participants achieving sustained virologic response 12 weeks after completing treatment (SVR12)

Primary: Percentage of participants experiencing an adverse event (AE)

Primary: Percentage of participants experiencing an adverse event (AE)

Primary: Percentage of participants discontinuing from study treatment due to an AE

Primary: Percentage of participants discontinuing from study treatment due to an AE

Secondary: Percentage of participants achieving Sustained Virologic Response 24 weeks after ending study treatment (SVR24)

Secondary: Percentage of participants achieving Sustained Virologic Response 24 weeks after ending study treatment (SVR24)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-3682 with Either MK-8742 or MK-8408 in Subjects with Chronic HCV GT1 and GT2 Infection