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Clinical Trial Results:
A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-Administration of ABT-493 and ABT-530 With and Without RBV in Subjects With Chronic Hepatitis C Virus (HCV) Genotypes 2, 3, 4, 5 or 6 Infection (SURVEYOR-II)

Summary
EudraCT number	2014-002927-90
Trial protocol	GB
Global end of trial date	23 Feb 2017

Results information
Results version number	v1(current)
This version publication date	19 Jan 2018
First version publication date	19 Jan 2018
Other versions

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

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Trial information

Top of page

Sponsor protocol code

M14-868

ISRCTN number

US NCT number

NCT02243293

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie Deutschland GmbH & Co.KG

Sponsor organisation address

AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB

Public contact

Global Medical Services, AbbVie, 001 800-633-9110,

Scientific contact

Stanley Wang, AbbVie, stanley.wang@abbvie.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

23 Feb 2017

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

23 Feb 2017

Was the trial ended prematurely?

Main objective of the trial

The purpose of this phase 2/3, open-label, multipart, multicenter study was to evaluate the efficacy, and safety of coadministration of ABT-493 and ABT-530 with and without ribavirin (RBV) in chronic HCV genotype 2 (GT2-), genotype 3 (GT3-), genotype 4 (GT4), genotype 5 (GT5-), or genotype 6 (GT6-) infected participants with or without cirrhosis.

Protection of trial subjects

Subject and/or legal guardian read and understood the information provided about the study and gave written permission.

Background therapy

Evidence for comparator

Actual start date of recruitment

19 Sep 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 65

Country: Number of subjects enrolled

Canada: 54

Country: Number of subjects enrolled

France: 3

Country: Number of subjects enrolled

Korea, Republic of: 5

Country: Number of subjects enrolled

New Zealand: 62

Country: Number of subjects enrolled

Taiwan: 3

Country: Number of subjects enrolled

United Kingdom: 9

Country: Number of subjects enrolled

United States: 493

Worldwide total number of subjects

694

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

618

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Enrollment into arms H, I, K, M and N was not opened by AbbVie.

Screening details

Intent-to-treat population: all participants who received at least 1 dose of study drug.

Period 1 title

Overall Study (As Treated) (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Arm A

Arm description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 2 (GT2) -infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

300 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Arm B

Arm description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Arm C

Arm description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and weight-based ribavirin (RBV) divided twice daily (BID) for 12 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Investigational medicinal product name

ribavirin (RBV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Weight-based ribavirin (RBV) divided twice daily (BID).

Arm D

Arm description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 3 (GT3) -infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

300 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Arm E

Arm description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Arm F

Arm description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and weight-based ribavirin (RBV) divided BID for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Investigational medicinal product name

ribavirin (RBV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Weight-based ribavirin (RBV) divided twice daily (BID).

Arm G

Arm description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (40 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (40 mg) once daily (QD)

Arm J

Arm description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

300 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Arm L

Arm description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT3 -infected treatment naïve and for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

300 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Arm O

Arm description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve participants with compensated cirrhosis and for 16 weeks in HCV GT3 -infected treatment-experienced participants with compensated cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

300 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Arm P

Arm description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD and RBV (800 mg) QD for 12 weeks in HCV GT3-infected treatment naïve and treatment-experienced participants with compensated cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493

Investigational medicinal product code

Other name

glecaprevir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

300 mg once daily (QD)

Investigational medicinal product name

ABT-530

Investigational medicinal product code

Other name

pibrentasvir

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-530 (120 mg) once daily (QD)

Investigational medicinal product name

ribavirin (RBV)

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ribavirin (RBV) 800 mg once daily (QD).

Arm Q1

Arm description

ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment naïve participants with cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493/ABT-530

Investigational medicinal product code

Other name

ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVIRET

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-493 (300 mg) co-formulated ABT-530 (120 mg) once daily (QD)

Arm Q2

Arm description

ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493/ABT-530

Investigational medicinal product code

Other name

ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVIRET

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-493 (300 mg) co-formulated ABT-530 (120 mg) once daily (QD)

Arm R1

Arm description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493/ABT-530

Investigational medicinal product code

Other name

ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVIRET

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-493 (300 mg) co-formulated ABT-530 (120 mg) once daily (QD)

Arm R2

Arm description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants with cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493/ABT-530

Investigational medicinal product code

Other name

ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVIRET

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-493 (300 mg) co-formulated ABT-530 (120 mg) once daily (QD)

Arm S1

Arm description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT2 infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493/ABT-530

Investigational medicinal product code

Other name

ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVIRET

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-493 (300 mg) co-formulated ABT-530 (120 mg) once daily (QD)

Arm S2

Arm description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT4-6 infected treatment naïve and treatment experienced participants without cirrhosis.

Arm type

Experimental

Investigational medicinal product name

ABT-493/ABT-530

Investigational medicinal product code

Other name

ABT-493 also known as glecaprevir, ABT-530 also known as pibrentasvir, MAVIRET

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ABT-493 (300 mg) co-formulated ABT-530 (120 mg) once daily (QD)

Number of subjects in period 1 ^[1]	Arm A	Arm B	Arm C	Arm D	Arm E	Arm F	Arm G	Arm J	Arm L	Arm O	Arm P	Arm Q1	Arm Q2	Arm R1	Arm R2	Arm S1	Arm S2
Started	25	24	25	30	30	31	30	54	53	28	27	40	22	22	47	145	58
Completed	23	23	24	29	30	31	27	53	50	27	26	37	21	22	47	143	55
Not completed	2	1	1	1	0	0	3	1	3	1	1	3	1	0	0	2	3
Consent withdrawn by subject	1	-	-	-	-	-	-	1	1	-	-	-	-	-	-	-	1
Enrolled into a Re-treatment Study	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-
Adverse event	1	-	-	-	-	-	-	-	-	-	1	-	-	-	-	1	-
Lost to follow-up	-	1	1	1	-	-	3	-	2	-	-	3	1	-	-	1	2

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The subject disposition section refers only to the subjects who have received study drug. Three subjects (1 subject each in arms E, J and R2 respectively) were randomized but didn't receive study drug.

Baseline characteristics

Top of page

Reporting group title

Arm A

Reporting group description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 2 (GT2) -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm B

Reporting group description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm C

Reporting group description

Reporting group title

Arm D

Reporting group description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 3 (GT3) -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm E

Reporting group description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm F

Reporting group description

Reporting group title

Arm G

Reporting group description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (40 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm J

Reporting group description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm L

Reporting group description

Reporting group title

Arm O

Reporting group description

Reporting group title

Arm P

Reporting group description

Reporting group title

Arm Q1

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment naïve participants with cirrhosis.

Reporting group title

Arm Q2

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Reporting group title

Arm R1

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Reporting group title

Arm R2

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants with cirrhosis.

Reporting group title

Arm S1

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT2 infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm S2

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT4-6 infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group values	Arm A	Arm B	Arm C	Arm D	Arm E	Arm F	Arm G	Arm J	Arm L	Arm O	Arm P	Arm Q1	Arm Q2	Arm R1	Arm R2	Arm S1	Arm S2	Total
Number of subjects	25	24	25	30	30	31	30	54	53	28	27	40	22	22	47	145	58	691
Age categorical
All participants who received atleast 1 dose of study drug (ITT population) are analyzed.
Units: Subjects
< 65 years	21	21	22	28	29	30	28	44	52	26	24	38	18	19	39	128	49	616
>= 65 years	4	3	3	2	1	1	2	10	1	2	3	2	4	3	8	17	9	75
Gender categorical
All participants who received atleast 1 dose of study drug (ITT population) are analyzed.
Units: Subjects
Female	9	11	7	11	16	12	15	21	21	13	9	16	8	8	11	84	21	293
Male	16	13	18	19	14	19	15	33	32	15	18	24	14	14	36	61	37	398

End points

Top of page

Reporting group title

Arm A

Reporting group description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 2 (GT2) -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm B

Reporting group description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm C

Reporting group description

Reporting group title

Arm D

Reporting group description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV genotype 3 (GT3) -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm E

Reporting group description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm F

Reporting group description

Reporting group title

Arm G

Reporting group description

ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (40 mg) QD for 12 weeks in HCV GT3 -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm J

Reporting group description

ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in HCV GT2 -infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm L

Reporting group description

Reporting group title

Arm O

Reporting group description

Reporting group title

Arm P

Reporting group description

Reporting group title

Arm Q1

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment naïve participants with cirrhosis.

Reporting group title

Arm Q2

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120mg ) once daily (QD) for 12 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Reporting group title

Arm R1

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants without cirrhosis.

Reporting group title

Arm R2

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 16 weeks in HCV GT3 -infected treatment experienced participants with cirrhosis.

Reporting group title

Arm S1

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT2 infected treatment naïve and treatment experienced participants without cirrhosis.

Reporting group title

Arm S2

Reporting group description

ABT-493/ ABT-530 (300 mg/ 120 mg) QD for 8 weeks in HCV GT4-6 infected treatment naïve and treatment experienced participants without cirrhosis.

Primary: Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)

Top of page

End point title

Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) ^[1]

End point description

SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug.

End point type

Primary

End point timeframe

12 weeks after the last actual dose of study drug

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive data are summarized for this end point per protocol.

Arm A

Arm B

Arm C

Arm D

Arm E

Arm F

Arm G

Arm J

Arm L

Arm O

Arm P

Arm Q1

Arm Q2

Arm R1

Arm R2

Arm S1

Arm S2

Number of subjects analysed

25 ^[2]

24 ^[3]

25 ^[4]

30 ^[5]

30 ^[6]

31 ^[7]

30 ^[8]

54 ^[9]

53 ^[10]

27 ^[11]

40 ^[12]

22 ^[13]

22 ^[14]

47 ^[15]

145 ^[16]

58 ^[17]

Units: percentage of participants

number (confidence interval 95%)

96.0 (80.5 to 99.3)

100.0 (86.2 to 100.0)

100.0 (86.7 to 100.0)

93.3 (78.7 to 98.2)

93.5 (79.3 to 98.2)

83.3 (66.4 to 92.7)

98.1 (90.2 to 99.7)

94.3 (84.6 to 98.1)

96.4 (82.3 to 99.4)

100.0 (87.5 to 100.0)

97.5 (87.1 to 99.6)

90.9 (72.2 to 97.5)

95.5 (78.2 to 99.2)

95.7 (85.8 to 98.8)

97.9 (94.1 to 99.3)

93.1 (83.6 to 97.3)

Notes
[2] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[3] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[4] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[5] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[6] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[7] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[8] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[9] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[10] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[11] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[12] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[13] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[14] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[15] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[16] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[17] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.

No statistical analyses for this end point

Primary: Percentage of Genotype 2 (GT2) Direct-acting Antiviral Agents (DAA)-Naive Participants (in Part 4, Arm S1) With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) as Compared to Historical Control

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End point title

Percentage of Genotype 2 (GT2) Direct-acting Antiviral Agents (DAA)-Naive Participants (in Part 4, Arm S1) With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) as Compared to Historical Control ^[18] ^[19]

End point description

SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug.

End point type

Primary

End point timeframe

12 weeks after the last actual dose of study drug

Notes
[18] - 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: The percentage of subjects (95% CI, calculated using the normal approximation to the binomial distribution) achieving SVR12 was 98.5% (96.5 to 100.0). The non-inferiority of the rate of SVR12 as compared to historical control (in genotype 2 (GT2) DAA-naive participants in Part 4, arm S1) was analyzed; the lower confidence bound of the 2-sided 95% confidence interval (95% CI) for the percentage of participants with SVR12 must exceed 89% to achieve non-inferiority.
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint was analyzed only in subjects in genotype 2 (GT2) DAA-Naive Participants (in Part 4, Arm S1).

End point values	Arm S1
Number of subjects analysed	137 ^[20]
Units: percentage of participants
number (confidence interval 95%)	98.5 (96.5 to 100.0)

Notes
[20] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.

No statistical analyses for this end point

Secondary: Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4)

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End point title

Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4)

End point description

SVR4 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 4 weeks after the last dose of study drug.

End point type

Secondary

End point timeframe

4 weeks after the last actual dose of study drug

Arm A

Arm B

Arm C

Arm D

Arm E

Arm F

Arm G

Arm J

Arm L

Arm O

Arm P

Arm Q1

Arm Q2

Arm R1

Arm R2

Arm S1

Arm S2

Number of subjects analysed

25 ^[21]

24 ^[22]

25 ^[23]

30 ^[24]

30 ^[25]

31 ^[26]

30 ^[27]

54 ^[28]

53 ^[29]

28 ^[30]

27 ^[31]

40 ^[32]

22 ^[33]

22 ^[34]

47 ^[35]

145 ^[36]

58 ^[37]

Units: percentage of participants

number (confidence interval 95%)

96.0 (80.5 to 99.3)

100.0 (86.2 to 100.0)

100.0 (86.7 to 100.0)

93.3 (78.7 to 98.2)

93.5 (79.3 to 98.2)

93.3 (78.7 to 98.2)

98.1 (90.2 to 99.7)

96.2 (87.2 to 99.0)

96.4 (82.3 to 99.4)

100.0 (87.5 to 100.0)

97.5 (87.1 to 99.6)

95.5 (78.2 to 99.2)

95.7 (85.8 to 98.8)

97.9 (94.1 to 99.3)

98.3 (90.9 to 99.7)

Notes
[21] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[22] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[23] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[24] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[25] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[26] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[27] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[28] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[29] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[30] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[31] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[32] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[33] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[34] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[35] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[36] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.
[37] - All participants who received at least 1 dose of study drug; missing data imputed as nonresponders.

No statistical analyses for this end point

Secondary: Percentage of Participants With On-treatment Virologic Failure

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End point title

Percentage of Participants With On-treatment Virologic Failure

End point description

On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.

End point type

Secondary

End point timeframe

Up to end of treatment (treatment week 8, 12 or 16 depending on arm) or premature discontinuation from treatment

Arm A

Arm B

Arm C

Arm D

Arm E

Arm F

Arm G

Arm J

Arm L

Arm O

Arm P

Arm Q1

Arm Q2

Arm R1

Arm R2

Arm S1

Arm S2

Number of subjects analysed

25 ^[38]

24 ^[39]

25 ^[40]

30 ^[41]

30 ^[42]

31 ^[43]

30 ^[44]

54 ^[45]

53 ^[46]

28 ^[47]

27 ^[48]

40 ^[49]

22 ^[50]

22 ^[51]

47 ^[52]

145 ^[53]

58 ^[54]

Units: percentage of participants

number (confidence interval 95%)

0 (0.0 to 13.3)

0 (0.0 to 13.8)

0 (0.0 to 13.3)

0 (0.0 to 11.4)

3.2 (0.6 to 16.2)

3.3 (0.6 to 16.7)

0 (0.0 to 6.6)

1.9 (0.3 to 9.9)

0 (0.0 to 12.1)

0 (0.0 to 12.5)

0 (0.0 to 8.8)

0 (0.0 to 14.9)

2.1 (0.4 to 11.1)

0 (0.0 to 2.6)

0 (0.0 to 6.2)

Notes
[38] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[39] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[40] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[41] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[42] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[43] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[44] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[45] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[46] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[47] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[48] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[49] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[50] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[51] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[52] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[53] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.
[54] - All participants who received at least 1 dose of study drug (ITT population) with evaluable data.

No statistical analyses for this end point

Secondary: Percentage of Participants With Post-treatment Relapse

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End point title

Percentage of Participants With Post-treatment Relapse

End point description

Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment, excluding reinfection.

End point type

Secondary

End point timeframe

From the end of treatment through 12 weeks after the last dose of study drug

Arm A

Arm B

Arm C

Arm D

Arm E

Arm F

Arm G

Arm J

Arm L

Arm O

Arm P

Arm Q1

Arm Q2

Arm R1

Arm R2

Arm S1

Arm S2

Number of subjects analysed

24 ^[55]

24 ^[56]

25 ^[57]

29 ^[58]

30 ^[59]

28 ^[60]

28 ^[61]

53 ^[62]

51 ^[63]

28 ^[64]

27 ^[65]

39 ^[66]

22 ^[67]

22 ^[68]

46 ^[69]

144 ^[70]

57 ^[71]

Units: percentage of participants

number (confidence interval 95%)

0 (0.0 to 13.8)

0 (0.0 to 13.3)

3.4 (0.6 to 17.2)

6.7 (1.8 to 21.3)

0 (0.0 to 12.1)

7.1 (2.0 to 22.6)

0 (0.0 to 6.8)

2.0 (0.3 to 10.3)

3.6 (0.6 to 17.7)

0 (0.0 to 12.5)

0 (0.0 to 9.0)

9.1 (2.5 to 27.8)

4.5 (0.8 to 21.8)

2.2 (0.4 to 11.3)

1.4 (0.4 to 4.9)

0 (0.0 to 6.3)

Notes
[55] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[56] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[57] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[58] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[59] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[60] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[61] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[62] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[63] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[64] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[65] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[66] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[67] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[68] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[69] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[70] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.
[71] - ITT subjects with evaluable data, completed treatment, and had HCV RNA <LLOQ at the final treatment.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 20 weeks).

Adverse event reporting additional description

TEAEs and TESAEs are defined as any adverse event (AE) or serious adverse event (SAE) with an onset date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Arm A

Reporting group description

Reporting group title

Arm B

Reporting group description

Reporting group title

Arm C

Reporting group description

Reporting group title

Arm D

Reporting group description

Reporting group title

Arm E

Reporting group description

Reporting group title

Arm F

Reporting group description

Reporting group title

Arm G

Reporting group description

Reporting group title

Arm J

Reporting group description

Reporting group title

Arm L

Reporting group description

Reporting group title

Arm O

Reporting group description

Reporting group title

Arm P

Reporting group description

Reporting group title

Arm Q1

Reporting group description

Reporting group title

Arm Q2

Reporting group description

Reporting group title

Arm R1

Reporting group description

Reporting group title

Arm R2

Reporting group description

Reporting group title

Arm S1

Reporting group description

Reporting group title

Arm S2

Reporting group description

Arm A

Arm B

Arm C

Arm D

Arm E

Arm F

Arm G

Arm J

Arm L

Arm O

Arm P

Arm Q1

Arm Q2

Arm R1

Arm R2

Arm S1

Arm S2

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 25 (4.00%)

0 / 30 (0.00%)

2 / 31 (6.45%)

0 / 30 (0.00%)

1 / 54 (1.85%)

1 / 53 (1.89%)

2 / 28 (7.14%)

2 / 27 (7.41%)

1 / 40 (2.50%)

1 / 22 (4.55%)

3 / 47 (6.38%)

2 / 145 (1.38%)

1 / 58 (1.72%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

B-CELL LYMPHOMA

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

1 / 31 (3.23%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

COLON CANCER

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

1 / 40 (2.50%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

HEPATIC NEOPLASM

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

1 / 28 (3.57%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SQUAMOUS CELL CARCINOMA OF SKIN

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

1 / 47 (2.13%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

TIBIA FRACTURE

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

1 / 28 (3.57%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

ANGINA PECTORIS

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

1 / 47 (2.13%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

ATRIAL FIBRILLATION

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

1 / 25 (4.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

ANAEMIA

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

1 / 27 (3.70%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

UMBILICAL HERNIA

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

1 / 47 (2.13%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

CHOLECYSTITIS

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

1 / 145 (0.69%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

PLEURAL EFFUSION

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

DELUSIONAL DISORDER, UNSPECIFIED TYPE

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

1 / 27 (3.70%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

SCHIZOPHRENIA

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

1 / 22 (4.55%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

APPENDICITIS

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

1 / 53 (1.89%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

CELLULITIS

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

1 / 54 (1.85%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (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 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

1 / 31 (3.23%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

0 / 58 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

UROSEPSIS

subjects affected / exposed

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 25 (0.00%)

0 / 30 (0.00%)

0 / 31 (0.00%)

0 / 30 (0.00%)

0 / 54 (0.00%)

0 / 53 (0.00%)

0 / 28 (0.00%)

0 / 27 (0.00%)

0 / 40 (0.00%)

0 / 22 (0.00%)

0 / 47 (0.00%)

0 / 145 (0.00%)

1 / 58 (1.72%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Arm A	Arm B	Arm C	Arm D	Arm E	Arm F	Arm G	Arm J	Arm L	Arm O	Arm P	Arm Q1	Arm Q2	Arm R1	Arm R2	Arm S1	Arm S2
Total subjects affected by non serious adverse events
subjects affected / exposed	12 / 25 (48.00%)	11 / 24 (45.83%)	22 / 25 (88.00%)	19 / 30 (63.33%)	20 / 30 (66.67%)	23 / 31 (74.19%)	18 / 30 (60.00%)	26 / 54 (48.15%)	40 / 53 (75.47%)	20 / 28 (71.43%)	21 / 27 (77.78%)	30 / 40 (75.00%)	12 / 22 (54.55%)	13 / 22 (59.09%)	31 / 47 (65.96%)	78 / 145 (53.79%)	32 / 58 (55.17%)
Vascular disorders
HYPERTENSION
subjects affected / exposed	0 / 25 (0.00%)	1 / 24 (4.17%)	3 / 25 (12.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	1 / 54 (1.85%)	2 / 53 (3.77%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	2 / 145 (1.38%)	0 / 58 (0.00%)
occurrences all number	0	1	3	0	0	0	0	1	2	0	0	0	0	0	0	2	0
General disorders and administration site conditions
ENERGY INCREASED
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	0 / 30 (0.00%)	2 / 54 (3.70%)	0 / 53 (0.00%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	2	0	2	0	0	0	0	1	0	0	0	0
FATIGUE
subjects affected / exposed	2 / 25 (8.00%)	3 / 24 (12.50%)	10 / 25 (40.00%)	6 / 30 (20.00%)	5 / 30 (16.67%)	12 / 31 (38.71%)	2 / 30 (6.67%)	7 / 54 (12.96%)	15 / 53 (28.30%)	3 / 28 (10.71%)	8 / 27 (29.63%)	5 / 40 (12.50%)	4 / 22 (18.18%)	4 / 22 (18.18%)	16 / 47 (34.04%)	24 / 145 (16.55%)	13 / 58 (22.41%)
occurrences all number	3	3	10	6	5	13	3	7	15	3	8	6	4	4	17	25	13
FEELING HOT
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 47 (2.13%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	1	0	0
PYREXIA
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 30 (0.00%)	1 / 31 (3.23%)	2 / 30 (6.67%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	1 / 27 (3.70%)	0 / 40 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	0 / 47 (0.00%)	0 / 145 (0.00%)	1 / 58 (1.72%)
occurrences all number	0	0	0	1	0	1	2	0	0	0	1	0	0	1	0	0	1
Respiratory, thoracic and mediastinal disorders
COUGH
subjects affected / exposed	0 / 25 (0.00%)	1 / 24 (4.17%)	1 / 25 (4.00%)	1 / 30 (3.33%)	2 / 30 (6.67%)	4 / 31 (12.90%)	0 / 30 (0.00%)	1 / 54 (1.85%)	2 / 53 (3.77%)	0 / 28 (0.00%)	3 / 27 (11.11%)	1 / 40 (2.50%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	3 / 145 (2.07%)	5 / 58 (8.62%)
occurrences all number	0	1	1	1	2	5	0	1	2	0	3	1	0	0	0	3	5
DYSPNOEA
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	2 / 30 (6.67%)	0 / 30 (0.00%)	3 / 31 (9.68%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	1 / 27 (3.70%)	0 / 40 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	1	2	0	3	0	0	0	0	1	0	1	0	0	0	0
DYSPNOEA EXERTIONAL
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	3 / 25 (12.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	1 / 30 (3.33%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	3	0	0	2	1	0	1	0	0	0	0	0	0	0	0
NASAL CONGESTION
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	1 / 30 (3.33%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	1 / 47 (2.13%)	1 / 145 (0.69%)	0 / 58 (0.00%)
occurrences all number	0	0	2	0	1	0	0	0	1	0	0	0	1	0	1	1	0
OROPHARYNGEAL PAIN
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 30 (3.33%)	2 / 30 (6.67%)	0 / 31 (0.00%)	1 / 30 (3.33%)	0 / 54 (0.00%)	4 / 53 (7.55%)	1 / 28 (3.57%)	0 / 27 (0.00%)	0 / 40 (0.00%)	2 / 22 (9.09%)	1 / 22 (4.55%)	0 / 47 (0.00%)	2 / 145 (1.38%)	1 / 58 (1.72%)
occurrences all number	0	0	1	1	2	0	1	0	4	1	0	0	2	1	0	2	1
RESPIRATORY TRACT CONGESTION
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	1	0	0	0	0	0	0	0	0
RHINORRHOEA
subjects affected / exposed	0 / 25 (0.00%)	1 / 24 (4.17%)	2 / 25 (8.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	1 / 31 (3.23%)	1 / 30 (3.33%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	1 / 58 (1.72%)
occurrences all number	0	1	2	0	0	1	1	0	1	0	0	0	1	0	0	0	1
Psychiatric disorders
ANXIETY
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	1 / 30 (3.33%)	2 / 30 (6.67%)	0 / 31 (0.00%)	1 / 30 (3.33%)	4 / 54 (7.41%)	1 / 53 (1.89%)	0 / 28 (0.00%)	1 / 27 (3.70%)	0 / 40 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	3 / 47 (6.38%)	6 / 145 (4.14%)	2 / 58 (3.45%)
occurrences all number	0	0	2	1	2	0	1	4	1	0	1	0	1	0	3	6	2
DEPRESSION
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	2 / 30 (6.67%)	0 / 31 (0.00%)	2 / 30 (6.67%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	2 / 27 (7.41%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 47 (2.13%)	4 / 145 (2.76%)	1 / 58 (1.72%)
occurrences all number	0	0	0	0	3	0	2	0	0	0	2	0	0	0	1	4	1
EMOTIONAL DISORDER
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	2 / 27 (7.41%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
INSOMNIA
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	1 / 30 (3.33%)	2 / 30 (6.67%)	3 / 31 (9.68%)	1 / 30 (3.33%)	3 / 54 (5.56%)	5 / 53 (9.43%)	0 / 28 (0.00%)	5 / 27 (18.52%)	1 / 40 (2.50%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 47 (6.38%)	1 / 145 (0.69%)	2 / 58 (3.45%)
occurrences all number	0	0	2	1	2	3	1	3	5	0	5	1	0	0	3	1	2
IRRITABILITY
subjects affected / exposed	0 / 25 (0.00%)	1 / 24 (4.17%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	4 / 31 (12.90%)	0 / 30 (0.00%)	2 / 54 (3.70%)	0 / 53 (0.00%)	0 / 28 (0.00%)	4 / 27 (14.81%)	1 / 40 (2.50%)	0 / 22 (0.00%)	1 / 22 (4.55%)	1 / 47 (2.13%)	2 / 145 (1.38%)	0 / 58 (0.00%)
occurrences all number	0	1	1	0	0	4	0	2	0	0	4	1	0	1	1	2	0
MOOD SWINGS
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	1 / 30 (3.33%)	0 / 54 (0.00%)	3 / 53 (5.66%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	1 / 58 (1.72%)
occurrences all number	0	0	1	0	0	0	1	0	3	0	0	0	0	0	0	0	1
Investigations
BLOOD BILIRUBIN INCREASED
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 28 (3.57%)	1 / 27 (3.70%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 47 (2.13%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	1	0	0	2	0	0	0	1	1	0	0	0	1	0	0
BLOOD BILIRUBIN UNCONJUGATED INCREASED
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0
HAEMATOCRIT DECREASED
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	1 / 30 (3.33%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	2	1	0	0	0	0	0	0	0	0	0	0	0	0	0
HAEMOGLOBIN DECREASED
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	4 / 25 (16.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	4 / 31 (12.90%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	2 / 27 (7.41%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	5	0	0	5	0	0	0	0	2	0	0	0	0	0	0
WEIGHT DECREASED
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Nervous system disorders
DIZZINESS
subjects affected / exposed	2 / 25 (8.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	1 / 30 (3.33%)	5 / 31 (16.13%)	0 / 30 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	2 / 28 (7.14%)	4 / 27 (14.81%)	4 / 40 (10.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	1 / 47 (2.13%)	7 / 145 (4.83%)	2 / 58 (3.45%)
occurrences all number	2	0	0	1	1	5	0	0	1	2	4	4	1	0	1	8	2
DYSGEUSIA
subjects affected / exposed	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	0 / 30 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 28 (0.00%)	1 / 27 (3.70%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	3 / 145 (2.07%)	0 / 58 (0.00%)
occurrences all number	1	0	0	0	0	2	0	0	1	0	1	0	0	0	0	3	0
HEADACHE
subjects affected / exposed	1 / 25 (4.00%)	3 / 24 (12.50%)	6 / 25 (24.00%)	4 / 30 (13.33%)	3 / 30 (10.00%)	6 / 31 (19.35%)	5 / 30 (16.67%)	6 / 54 (11.11%)	17 / 53 (32.08%)	5 / 28 (17.86%)	9 / 27 (33.33%)	10 / 40 (25.00%)	5 / 22 (22.73%)	4 / 22 (18.18%)	6 / 47 (12.77%)	17 / 145 (11.72%)	11 / 58 (18.97%)
occurrences all number	1	3	6	4	3	8	5	7	20	5	11	11	5	4	6	19	14
HYPOAESTHESIA
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	1 / 27 (3.70%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 47 (2.13%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	1	0	0	0	1	0	0
MIGRAINE
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	2 / 54 (3.70%)	0 / 53 (0.00%)	1 / 28 (3.57%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	1 / 145 (0.69%)	0 / 58 (0.00%)
occurrences all number	0	0	3	0	0	0	0	2	0	1	0	0	0	0	0	1	0
Blood and lymphatic system disorders
ANAEMIA
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	0 / 47 (0.00%)	0 / 145 (0.00%)	1 / 58 (1.72%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	2	0	0	1
Ear and labyrinth disorders
EAR PAIN
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	0 / 27 (0.00%)	2 / 40 (5.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Gastrointestinal disorders
ABDOMINAL DISCOMFORT
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	4 / 53 (7.55%)	0 / 28 (0.00%)	2 / 27 (7.41%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	5	0	2	0	0	0	0	0	0
ABDOMINAL DISTENSION
subjects affected / exposed	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	2 / 54 (3.70%)	3 / 53 (5.66%)	2 / 28 (7.14%)	1 / 27 (3.70%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	1 / 145 (0.69%)	0 / 58 (0.00%)
occurrences all number	0	1	0	0	0	0	0	2	3	2	1	0	0	0	0	1	0
ABDOMINAL PAIN
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	0 / 30 (0.00%)	2 / 54 (3.70%)	3 / 53 (5.66%)	0 / 28 (0.00%)	2 / 27 (7.41%)	2 / 40 (5.00%)	2 / 22 (9.09%)	1 / 22 (4.55%)	2 / 47 (4.26%)	3 / 145 (2.07%)	2 / 58 (3.45%)
occurrences all number	0	0	0	0	0	2	0	2	4	0	2	2	2	1	3	3	2
ABDOMINAL PAIN LOWER
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	0 / 27 (0.00%)	2 / 40 (5.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	1 / 145 (0.69%)	1 / 58 (1.72%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	1
ABDOMINAL PAIN UPPER
subjects affected / exposed	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 30 (0.00%)	1 / 31 (3.23%)	0 / 30 (0.00%)	1 / 54 (1.85%)	1 / 53 (1.89%)	1 / 28 (3.57%)	0 / 27 (0.00%)	2 / 40 (5.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	1 / 47 (2.13%)	0 / 145 (0.00%)	1 / 58 (1.72%)
occurrences all number	1	0	0	1	0	1	0	1	1	1	0	2	0	1	1	0	1
CONSTIPATION
subjects affected / exposed	1 / 25 (4.00%)	1 / 24 (4.17%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	1 / 30 (3.33%)	3 / 54 (5.56%)	3 / 53 (5.66%)	0 / 28 (0.00%)	0 / 27 (0.00%)	1 / 40 (2.50%)	2 / 22 (9.09%)	0 / 22 (0.00%)	1 / 47 (2.13%)	4 / 145 (2.76%)	0 / 58 (0.00%)
occurrences all number	1	1	1	0	0	3	1	3	3	0	0	1	2	0	1	4	0
DIARRHOEA
subjects affected / exposed	4 / 25 (16.00%)	1 / 24 (4.17%)	6 / 25 (24.00%)	2 / 30 (6.67%)	1 / 30 (3.33%)	2 / 31 (6.45%)	2 / 30 (6.67%)	4 / 54 (7.41%)	8 / 53 (15.09%)	6 / 28 (21.43%)	1 / 27 (3.70%)	4 / 40 (10.00%)	1 / 22 (4.55%)	2 / 22 (9.09%)	1 / 47 (2.13%)	4 / 145 (2.76%)	2 / 58 (3.45%)
occurrences all number	4	1	7	3	1	3	2	4	9	6	1	4	1	2	1	4	2
DYSPEPSIA
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	3 / 25 (12.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	0 / 30 (0.00%)	0 / 54 (0.00%)	2 / 53 (3.77%)	1 / 28 (3.57%)	1 / 27 (3.70%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 47 (6.38%)	4 / 145 (2.76%)	2 / 58 (3.45%)
occurrences all number	0	0	3	0	0	3	0	0	2	2	1	0	0	0	4	4	2
GASTROOESOPHAGEAL REFLUX DISEASE
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	1 / 31 (3.23%)	0 / 30 (0.00%)	1 / 54 (1.85%)	1 / 53 (1.89%)	1 / 28 (3.57%)	0 / 27 (0.00%)	0 / 40 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	1 / 47 (2.13%)	2 / 145 (1.38%)	0 / 58 (0.00%)
occurrences all number	0	0	2	0	0	1	0	1	1	1	0	0	1	0	1	2	0
NAUSEA
subjects affected / exposed	3 / 25 (12.00%)	1 / 24 (4.17%)	8 / 25 (32.00%)	2 / 30 (6.67%)	6 / 30 (20.00%)	11 / 31 (35.48%)	0 / 30 (0.00%)	5 / 54 (9.26%)	4 / 53 (7.55%)	3 / 28 (10.71%)	7 / 27 (25.93%)	4 / 40 (10.00%)	2 / 22 (9.09%)	2 / 22 (9.09%)	5 / 47 (10.64%)	18 / 145 (12.41%)	5 / 58 (8.62%)
occurrences all number	3	1	9	2	6	11	0	6	5	3	7	4	2	2	5	20	7
TOOTHACHE
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	1 / 31 (3.23%)	0 / 30 (0.00%)	0 / 54 (0.00%)	4 / 53 (7.55%)	0 / 28 (0.00%)	1 / 27 (3.70%)	1 / 40 (2.50%)	0 / 22 (0.00%)	2 / 22 (9.09%)	0 / 47 (0.00%)	1 / 145 (0.69%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	4	0	1	1	0	2	0	1	0
VOMITING
subjects affected / exposed	0 / 25 (0.00%)	1 / 24 (4.17%)	3 / 25 (12.00%)	0 / 30 (0.00%)	1 / 30 (3.33%)	4 / 31 (12.90%)	2 / 30 (6.67%)	3 / 54 (5.56%)	2 / 53 (3.77%)	2 / 28 (7.14%)	1 / 27 (3.70%)	2 / 40 (5.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	2 / 145 (1.38%)	1 / 58 (1.72%)
occurrences all number	0	1	4	0	1	4	2	3	3	2	1	2	0	0	0	2	1
Skin and subcutaneous tissue disorders
DRY SKIN
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	2 / 27 (7.41%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 47 (2.13%)	0 / 145 (0.00%)	1 / 58 (1.72%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	2	0	0	0	1	0	1
PRURITUS
subjects affected / exposed	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	3 / 31 (9.68%)	1 / 30 (3.33%)	1 / 54 (1.85%)	4 / 53 (7.55%)	1 / 28 (3.57%)	2 / 27 (7.41%)	1 / 40 (2.50%)	2 / 22 (9.09%)	0 / 22 (0.00%)	1 / 47 (2.13%)	3 / 145 (2.07%)	1 / 58 (1.72%)
occurrences all number	1	0	1	0	0	3	1	1	5	1	2	1	2	0	1	4	1
RASH
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	2 / 25 (8.00%)	1 / 30 (3.33%)	1 / 30 (3.33%)	0 / 31 (0.00%)	1 / 30 (3.33%)	0 / 54 (0.00%)	3 / 53 (5.66%)	2 / 28 (7.14%)	0 / 27 (0.00%)	1 / 40 (2.50%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 47 (2.13%)	0 / 145 (0.00%)	1 / 58 (1.72%)
occurrences all number	0	0	3	1	1	0	1	0	3	2	0	1	0	0	1	0	1
Renal and urinary disorders
POLLAKIURIA
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	2 / 28 (7.14%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	2	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
ARTHRALGIA
subjects affected / exposed	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	1 / 31 (3.23%)	2 / 30 (6.67%)	2 / 54 (3.70%)	2 / 53 (3.77%)	0 / 28 (0.00%)	2 / 27 (7.41%)	1 / 40 (2.50%)	0 / 22 (0.00%)	2 / 22 (9.09%)	1 / 47 (2.13%)	2 / 145 (1.38%)	1 / 58 (1.72%)
occurrences all number	1	0	0	0	0	1	2	2	2	0	2	1	0	2	1	2	1
BACK PAIN
subjects affected / exposed	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	1 / 30 (3.33%)	0 / 31 (0.00%)	2 / 30 (6.67%)	3 / 54 (5.56%)	1 / 53 (1.89%)	0 / 28 (0.00%)	3 / 27 (11.11%)	4 / 40 (10.00%)	0 / 22 (0.00%)	4 / 22 (18.18%)	0 / 47 (0.00%)	6 / 145 (4.14%)	2 / 58 (3.45%)
occurrences all number	1	0	0	1	1	0	2	3	1	0	3	4	0	4	0	6	2
MUSCLE SPASMS
subjects affected / exposed	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	1 / 30 (3.33%)	0 / 30 (0.00%)	1 / 31 (3.23%)	0 / 30 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 28 (0.00%)	3 / 27 (11.11%)	1 / 40 (2.50%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	2 / 145 (1.38%)	0 / 58 (0.00%)
occurrences all number	1	0	1	1	0	1	0	0	1	0	3	1	0	0	0	2	0
MUSCULOSKELETAL PAIN
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	1 / 30 (3.33%)	0 / 54 (0.00%)	1 / 53 (1.89%)	2 / 28 (7.14%)	0 / 27 (0.00%)	1 / 40 (2.50%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	1 / 145 (0.69%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	2	0	1	0	0	0	1	0
MYALGIA
subjects affected / exposed	0 / 25 (0.00%)	1 / 24 (4.17%)	1 / 25 (4.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	2 / 31 (6.45%)	1 / 30 (3.33%)	0 / 54 (0.00%)	4 / 53 (7.55%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 47 (2.13%)	3 / 145 (2.07%)	2 / 58 (3.45%)
occurrences all number	0	1	1	0	0	2	1	0	4	0	0	0	0	0	1	3	2
NECK PAIN
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	2 / 30 (6.67%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 28 (0.00%)	0 / 27 (0.00%)	2 / 40 (5.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	1	0	0	2	0	1	0	0	0
Infections and infestations
BRONCHITIS
subjects affected / exposed	2 / 25 (8.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 30 (0.00%)	2 / 30 (6.67%)	1 / 31 (3.23%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	1 / 28 (3.57%)	1 / 27 (3.70%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	1 / 145 (0.69%)	0 / 58 (0.00%)
occurrences all number	2	0	1	0	2	1	0	0	0	1	1	0	0	0	0	1	0
GASTROENTERITIS
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	1 / 54 (1.85%)	0 / 53 (0.00%)	1 / 28 (3.57%)	2 / 27 (7.41%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	2	0	0	0	0	0	0
GASTROENTERITIS VIRAL
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	0 / 27 (0.00%)	2 / 40 (5.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	1 / 145 (0.69%)	0 / 58 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	2	0	0	0	1	0
LOWER RESPIRATORY TRACT INFECTION
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	1 / 27 (3.70%)	3 / 40 (7.50%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	3	0	0	0	0	0
NASOPHARYNGITIS
subjects affected / exposed	2 / 25 (8.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 30 (3.33%)	2 / 30 (6.67%)	0 / 31 (0.00%)	2 / 30 (6.67%)	1 / 54 (1.85%)	3 / 53 (5.66%)	0 / 28 (0.00%)	1 / 27 (3.70%)	2 / 40 (5.00%)	1 / 22 (4.55%)	1 / 22 (4.55%)	3 / 47 (6.38%)	6 / 145 (4.14%)	1 / 58 (1.72%)
occurrences all number	3	0	0	1	2	0	2	1	3	0	1	2	1	1	4	6	1
PHARYNGITIS
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 30 (3.33%)	0 / 31 (0.00%)	0 / 30 (0.00%)	0 / 54 (0.00%)	0 / 53 (0.00%)	0 / 28 (0.00%)	2 / 27 (7.41%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	0 / 145 (0.00%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0	0	0
SINUSITIS
subjects affected / exposed	1 / 25 (4.00%)	0 / 24 (0.00%)	4 / 25 (16.00%)	1 / 30 (3.33%)	2 / 30 (6.67%)	1 / 31 (3.23%)	0 / 30 (0.00%)	0 / 54 (0.00%)	1 / 53 (1.89%)	1 / 28 (3.57%)	1 / 27 (3.70%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	3 / 145 (2.07%)	0 / 58 (0.00%)
occurrences all number	1	0	4	1	3	1	0	0	1	1	1	0	0	0	0	3	0
TOOTH ABSCESS
subjects affected / exposed	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	1 / 31 (3.23%)	2 / 30 (6.67%)	0 / 54 (0.00%)	1 / 53 (1.89%)	0 / 28 (0.00%)	0 / 27 (0.00%)	0 / 40 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	0 / 47 (0.00%)	1 / 145 (0.69%)	0 / 58 (0.00%)
occurrences all number	0	0	0	0	0	1	2	0	1	0	0	0	0	0	0	1	0
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 25 (4.00%)	1 / 24 (4.17%)	5 / 25 (20.00%)	4 / 30 (13.33%)	1 / 30 (3.33%)	1 / 31 (3.23%)	1 / 30 (3.33%)	1 / 54 (1.85%)	4 / 53 (7.55%)	5 / 28 (17.86%)	2 / 27 (7.41%)	3 / 40 (7.50%)	1 / 22 (4.55%)	0 / 22 (0.00%)	2 / 47 (4.26%)	10 / 145 (6.90%)	3 / 58 (5.17%)
occurrences all number	1	1	5	4	1	1	1	1	5	5	2	3	1	0	2	10	3
URINARY TRACT INFECTION
subjects affected / exposed	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 25 (0.00%)	0 / 30 (0.00%)	1 / 30 (3.33%)	0 / 31 (0.00%)	1 / 30 (3.33%)	1 / 54 (1.85%)	0 / 53 (0.00%)	1 / 28 (3.57%)	1 / 27 (3.70%)	2 / 40 (5.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	1 / 47 (2.13%)	7 / 145 (4.83%)	0 / 58 (0.00%)
occurrences all number	0	2	0	0	1	0	1	1	0	1	1	2	0	1	1	7	0
Metabolism and nutrition disorders
DECREASED APPETITE
subjects affected / exposed	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	0 / 30 (0.00%)	0 / 30 (0.00%)	1 / 31 (3.23%)	1 / 30 (3.33%)	1 / 54 (1.85%)	0 / 53 (0.00%)	2 / 28 (7.14%)	0 / 27 (0.00%)	1 / 40 (2.50%)	0 / 22 (0.00%)	1 / 22 (4.55%)	2 / 47 (4.26%)	3 / 145 (2.07%)	3 / 58 (5.17%)
occurrences all number	1	0	0	0	0	1	1	1	0	2	0	1	0	1	2	3	3

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Were there any global substantial amendments to the protocol? Yes

08 Aug 2014

The purpose of this amendment was as follows: - Added Arm G to evaluate ABT-493 (200 mg) once daily (QD) and ABT-530 (40 mg) QD in treatment-naïve and pegylated interferon/ribavirin experienced HCV GT3-infected subjects. - Extended Screening Period duration limit from 35 to 42 days to minimize the risk of screen failing subjects due to screening window duration.

11 Nov 2014

The purpose of this amendment was as follows: - Removed 60% enrollment cap on treatment-naïve (TN) subjects. - Clarified the assessment of adverse events (AE) relatedness to the AbbVie direct-acting antiviral agent (DAAs) and ribavirin (RBV). - Updated the resistance analyses to include phylogenetic analysis of viral subtypes so that treatment efficacy (sustained virologic response 12 weeks postdosing, SVR12) could be compared across the different subtypes in the study.

20 Feb 2015

The purpose of this amendment was as follows: - Added new genotype (GT) 2 arm (Arm J) to evaluate ABT-493 (300 mg) + ABT-530 (120 mg) to understand if a higher dose of ABT-493 in combination with ABT-530 (120 mg) would result in improved sustained virologic response (SVR) while maintaining safety and tolerability. - Changed doses to be evaluated in GT3 Arms L, O, and P (Part 2) from ABT-493 (200 mg) + ABT-530 (40 mg) to ABT-493 (300 mg) + ABT-530 (120 mg) to understand if a higher dose of ABT-493 in combination with ABT-530 (120 mg) would result in improved SVR for 8-week treatment durations in subjects without cirrhosis or in a harder-to-treat population (subjects with cirrhosis) with a 12-week treatment duration. - Added a potential method (deep sequencing) to sequence hepatitis C virus (HCV) samples.

26 Feb 2015

The purpose of this amendment was as follows: - Clarified efficacy enablement criteria to enable enrollment of Arm I for GT2-infected subjects and Arms K, M, and N for GT3-infected subjects. - Clarified that safety enablement criteria were dependent on the number of subjects with AEs (with reasonable possibility of being related to the DAAs) leading to study drug discontinuation.

10 Apr 2015

The purpose of this amendment was as follows: - Modified ABT-530 dose for Arms M and N to be evaluated in combination with 200 mg ABT-493 in GT3-infected cirrhotic cohorts to understand if an 80 mg dose of ABT-530 would maintain high SVR rates while maximizing the safety and tolerability of the regimen. - Provided additional data for the ABT-493 exposure- alanine aminotransferase (ALT) level and ABT-493 exposure-total bilirubin level relationships with respect to Grade 2 ALT and total bilirubin elevations, respectively. - Updated aminotransferase/platelet ratio index (APRI) cutoff value in Inclusion Criterion for defining noncirrhotic in Part 2 to reflect a more accurate APRI cutoff value. - Updated text in Exclusion Criterion and added justification to allow enrollment of subjects on stable opioid replacement therapy of methadone or buprenorphine ± naloxone for at least 6 months prior to screening following availability of preliminary pharmacokinetic, pharmacodynamic, and safety data from Study M13-602. - Provided clarification on the requirements for additional liver diagnostic testing in subjects in Part 2 with a previous diagnosis of cirrhosis by biopsy. - Clarified toxicity management and additional clinical guidance with respect to ribavirin (RBV) dose modification.

03 Sep 2015

The purpose of this amendment was as follows: - Updated preliminary results for Part 1 and enrollment status of Part 2. - Updated the sample size for Arm J in Part 2 to accurately reflect the enrollment numbers. - Increased the sample size for Arm L in Part 2 and extend treatment duration for pegylated interferon/ribavirin (PR)-experienced subjects in Arm L to 12 weeks. - Restricted enrollment of Arms M – P (12 week treatment duration) in Part 2 to treatment-naïve (TN) cirrhotic subjects and extended the treatment duration for treatment-experienced (TE) cirrhotic subjects previously enrolled in Arm O under Protocol Amendment 5 to 16 weeks to determine the optimal dosing regimen in cirrhotic subjects who were TN. - Updated inclusion criteria for TE subjects in Part 2. - Updated AE collection period to reflect the continued collection of serious adverse events (SAEs) from 30 days after drug stopped through the end of the study.

30 Sep 2015

The purpose of this amendment was as follows: - Updated with preliminary results for Part 2 of the study. - Added study design for Part 3 and prespecified criteria to enable Part 3 evaluation. - Expanded the eligibility criteria for enrollment of subjects in Part 3 to facilitate evaluation of subjects' representative of the targeted HCV-infected population and to broaden the definition of treatment experience to include those who previously received sofosbuvir plus ribavirin with or without pegylated interferon therapy. - Updated text describing the use of coformulated ABT-493/ABT-530 tablets in Part 3 (dosing and the requirement to take the tablets with food). - Updated the management of increases in alanine aminotransferase (ALT) for Part 3 to reflect inclusion of HCV-infected patients with ALT levels up to < 10 upper limit of normal (ULN). - Provided clarification regarding management of prohibited therapy and concomitant medications. - Updated Inclusion Criteria and urine pregnancy test requirements for Part 3 of the study to provide time requirements for effective methods of contraception during the study and frequency of urine pregnancy tests in the Post-Treatment Period for subjects in Part 3 who were no longer being administered RBV. Provided a list of the effective methods of birth control for subjects and their partners. - Updated Inclusion Criterion with regards to FibroScan requirements in Part 3 to allow any historical FibroScan for subjects with an existing diagnosis of cirrhosis prior to screening. - Clarified the treatment extension criteria for subjects in Part 2 and provided the treatment extension criteria for subjects in Part 3.

16 Dec 2015

The purpose of this amendment was as follows: - Updated with preliminary results for Part 2 of the study and clarified that Arms M and N in Part 2 would not be opened. - Specified which arms and GT3-infected subpopulations would be evaluated in Part 3, based on the supporting data from Part 2. - Added study design for Part 4 based on data from Study M14-867 and Arm J in Part 2. - Updated Inclusion Criteria, and Exclusion Criteria to clarify that subjects without cirrhosis enrolled in Part 3 had to be TE, to clarify the methods for assessment of liver fibrosis in the setting of an indeterminate Fibrotest score, and to clarify which cohorts and parts the laboratory eligibility criteria were applicable to. - Clarified treatment extension criteria for subjects in Part 3 and provided the treatment extension criteria for subjects in Part 4. - Updated guidance for the investigator in the setting of a subject pregnancy in Parts 3 and 4, in which RBV was not administered. Clarified the time period during the study for which female subjects and male subjects (and their female partners) were to avoid pregnancy. - Clarified that Sanger sequencing would be performed in the setting of a result of "unable to genotype" but not for "unable to subtype."

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

http://www.ncbi.nlm.nih.gov/pubmed/27456384

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Clinical Trial Results:
A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-Administration of ABT-493 and ABT-530 With and Without RBV in Subjects With Chronic Hepatitis C Virus (HCV) Genotypes 2, 3, 4, 5 or 6 Infection (SURVEYOR-II)

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Baseline characteristics

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Primary: Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)

Primary: Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)

Primary: Percentage of Genotype 2 (GT2) Direct-acting Antiviral Agents (DAA)-Naive Participants (in Part 4, Arm S1) With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) as Compared to Historical Control

Primary: Percentage of Genotype 2 (GT2) Direct-acting Antiviral Agents (DAA)-Naive Participants (in Part 4, Arm S1) With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) as Compared to Historical Control

Secondary: Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4)

Secondary: Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4)

Secondary: Percentage of Participants With On-treatment Virologic Failure

Secondary: Percentage of Participants With On-treatment Virologic Failure

Secondary: Percentage of Participants With Post-treatment Relapse

Secondary: Percentage of Participants With Post-treatment Relapse

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Clinical trials

Clinical Trial Results: A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-Administration of ABT-493 and ABT-530 With and Without RBV in Subjects With Chronic Hepatitis C Virus (HCV) Genotypes 2, 3, 4, 5 or 6 Infection (SURVEYOR-II)

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Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)

Primary: Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)

Primary: Percentage of Genotype 2 (GT2) Direct-acting Antiviral Agents (DAA)-Naive Participants (in Part 4, Arm S1) With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) as Compared to Historical Control

Primary: Percentage of Genotype 2 (GT2) Direct-acting Antiviral Agents (DAA)-Naive Participants (in Part 4, Arm S1) With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) as Compared to Historical Control

Secondary: Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4)

Secondary: Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4)

Secondary: Percentage of Participants With On-treatment Virologic Failure

Secondary: Percentage of Participants With On-treatment Virologic Failure

Secondary: Percentage of Participants With Post-treatment Relapse

Secondary: Percentage of Participants With Post-treatment Relapse

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

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Clinical Trial Results:
A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Co-Administration of ABT-493 and ABT-530 With and Without RBV in Subjects With Chronic Hepatitis C Virus (HCV) Genotypes 2, 3, 4, 5 or 6 Infection (SURVEYOR-II)