Dose-Ranging Study of Sofosbuvir in Combination With Pegy... | NCT01054729

Label	Type	Description	Intervention Names
Sofosbuvir 100 mg+PEG+RBV	Experimental	Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)	Drug: Sofosbuvir Drug: PEG Drug: RBV
Sofosbuvir 200 mg+PEG+RBV	Experimental	Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)	Drug: Sofosbuvir Drug: PEG Drug: RBV
Sofosbuvir 400 mg+PEG+RBV	Experimental	Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)	Drug: Sofosbuvir Drug: PEG Drug: RBV
Placebo+PEG+RBV	Active Comparator	Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)	Drug: Placebo Drug: PEG Drug: RBV

Name	Type	Description	Arm Group Labels	Other Names
Sofosbuvir	Drug	Sofosbuvir tablet(s) administered orally once daily	Sofosbuvir 100 mg+PEG+RBV Sofosbuvir 200 mg+PEG+RBV Sofosbuvir 400 mg+PEG+RBV

Measure	Description	Time Frame
Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period	Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.	Baseline to Week 4

Measure	Description	Time Frame
Change in Circulating HCV RNA at Week 4		Baseline to Week 4
Percentage of Participants With Rapid Virologic Response at Week 4	Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD [15 IU/mL]) at Week 4.

Name	Affiliation	Role
Robert H. Hyland, DPhil	Gilead Sciences	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Quest Clinical Research		San Francisco	California	94115	United States
University of Florida

ID	Title	Description
FG000	Sofosbuvir 100 mg+PEG+RBV	Participants received sofosbuvir 100 mg for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)
FG001	Sofosbuvir 200 mg+PEG+RBV	Participants received sofosbuvir 200 mg for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)

ID	Title	Description
BG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
BG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
BG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks
BG003	Placebo+PEG+RBV	Placebo to match sofosbuvir for 28 days plus PEG+RBV for 48 weeks
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00016 BG00118 BG00215 BG00314 BG00463

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period

Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.

Safety Analysis Set: participants were randomized and received at least 1 dose of study drug

Posted

Number

percentage of participants

Baseline to Week 4

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks
OG003	Placebo+PEG+RBV	Placebo to match sofosbuvir for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants	OG00016 OG00118 OG00215 OG003

Title

Denominators

Categories

Any AE

Title	Measurements
	OG00087.5 OG00183.3 OG00286.7 OG003

Secondary

Change in Circulating HCV RNA at Week 4

Safety Analysis Set

Posted

Mean

Standard Deviation

log10 IU/mL

Baseline to Week 4

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks
OG003	Placebo+PEG+RBV	Placebo to match sofosbuvir for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Percentage of Participants With Rapid Virologic Response at Week 4

Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD [15 IU/mL]) at Week 4.

Safety Analysis Set

Posted

Number

percentage of participants

Week 4

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks
OG003	Placebo+PEG+RBV	Placebo to match sofosbuvir for 28 days plus PEG+RBV for 48 weeks

Units	Counts

Secondary

Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment

SVR at 12 weeks (SVR12) and 24 weeks (SVR24) was defined as HCV RNA < LOD 12 and 24 weeks after last dose of PEG+RBV, respectively, following completion of 48 weeks of treatment (4 weeks of sofosbuvir or matching placebo and PEG+RBV, followed by an additional 44 weeks of PEG+RBV).

Safety Analysis Set

Posted

Number

percentage of participants

Post-treatment Weeks 12 and 24

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks
OG003	Placebo+PEG+RBV	Placebo to match sofosbuvir for 28 days plus PEG+RBV for 48 weeks

Secondary

Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0

The Cmax of sofosbuvir was measured at Day 0 following a single dose of sofosbuvir.

Cmax is defined as the maximum concentration of drug.

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27

The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0

The AUCinf of sofosbuvir was analyzed at Day 0 (following a single dose of sofosbuvir).

AUCinf is defined as the concentration of drug (area under the plasma concentration versus time curve) extrapolated to infinite time.

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

h*ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27

The AUCtau of sofosbuvir was analyzed at Day 27 (following continuous dosing of sofosbuvir).

AUCtau is defined as the concentration of drug (area under the plasma concentration versus time curve) over the dosing interval.

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

h*ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of GS-331007: Cmax at Day 0

The Cmax of GS-331007 was measured at Day 0 following a single dose of sofosbuvir. GS-331007 is the predominant circulating metabolite of sofosbuvir.

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of GS-331007: Cmax at Day 27

The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0

The AUCinf of GS-331007 was analyzed at Day 0 (following a single dose of sofosbuvir).

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

h*ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27

The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

h*ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of GS-566500: Cmax at Day 0

The Cmax of GS-566500 was measured at Day 0 following a single dose of sofosbuvir. GS-566500 is one of the major metabolites of sofosbuvir.

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of GS-566500: Cmax at Day 27

The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0

The AUCinf of GS-566500 was analyzed at Day 0 (following a single dose of sofosbuvir).

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

h*ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27

The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).

Participants in the Safety Analysis Set with available data and who received a regimen containing sofosbuvir were analyzed.

Posted

Mean

Standard Deviation

h*ng/mL

Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose)

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants

Secondary

Percentage of Participants Who Developed Resistance to Sofosbuvir

Participants in the Safety Analysis Set who received a regimen containing sofosbuvir were analyzed.

Posted

Number

percentage of participants

Baseline to Week 4

ID	Title	Description
OG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks
OG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks
OG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks

Units	Counts
Participants	OG000

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0018 affected18 at risk EG0021 affected15 at risk EG0031 affected14 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0013 affected18 at risk EG0020 affected15 at risk EG003
Motion sickness	Ear and labyrinth disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Blepharitis	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Dry eye	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Eye pain	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Presbyopia	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Retinal vasculitis	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Retinitis	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Visual acuity reduced	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0011 affected18 at risk EG0022 affected15 at risk EG003
Visual impairment	Eye disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0022 affected15 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Aphthous stomatitis	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0021 affected15 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0021 affected15 at risk EG003
Glossodynia	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0005 affected16 at risk EG0016 affected18 at risk EG0029 affected15 at risk EG003
Retching	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0023 affected15 at risk EG003
Asthenia	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Chills	General disorders	MedDRA (13.0)	Systematic Assessment	EG0007 affected16 at risk EG0016 affected18 at risk EG0024 affected15 at risk EG003
Fatigue	General disorders	MedDRA (13.0)	Systematic Assessment	EG0007 affected16 at risk EG0018 affected18 at risk EG0029 affected15 at risk EG003
Injection site erythema	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0012 affected18 at risk EG0020 affected15 at risk EG003
Injection site irritation	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Injection site reaction	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0011 affected18 at risk EG0021 affected15 at risk EG003
Irritability	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Pain	General disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0012 affected18 at risk EG0021 affected15 at risk EG003
Pyrexia	General disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected16 at risk EG0011 affected18 at risk EG0021 affected15 at risk EG003
Bronchitis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Cellulitis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Impetigo	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Sinusitis	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Weight increased	Investigations	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (13.0)	Systematic Assessment	EG0003 affected16 at risk EG0011 affected18 at risk EG0023 affected15 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0007 affected16 at risk EG0012 affected18 at risk EG0023 affected15 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0022 affected15 at risk EG003
Muscle fatigue	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0022 affected15 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0004 affected16 at risk EG0011 affected18 at risk EG0022 affected15 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Balance disorder	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Dizziness	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected16 at risk EG0011 affected18 at risk EG0023 affected15 at risk EG003
Headache	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0004 affected16 at risk EG0016 affected18 at risk EG0025 affected15 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Sinus headache	Nervous system disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Affect lability	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0012 affected18 at risk EG0021 affected15 at risk EG003
Anxiety	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0002 affected16 at risk EG0011 affected18 at risk EG0023 affected15 at risk EG003
Daydreaming	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Depression	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0012 affected18 at risk EG0022 affected15 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0005 affected16 at risk EG0013 affected18 at risk EG0023 affected15 at risk EG003
Mood swings	Psychiatric disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0021 affected15 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Sexual dysfunction	Reproductive system and breast disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0022 affected15 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0012 affected18 at risk EG0021 affected15 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0013 affected18 at risk EG0021 affected15 at risk EG003
Pleuritic pain	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0003 affected16 at risk EG0012 affected18 at risk EG0021 affected15 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Hair texture abnormal	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0003 affected16 at risk EG0013 affected18 at risk EG0025 affected15 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0010 affected18 at risk EG0021 affected15 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0012 affected18 at risk EG0020 affected15 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA (13.0)	Systematic Assessment	EG0000 affected16 at risk EG0011 affected18 at risk EG0020 affected15 at risk EG003
Flushing	Vascular disorders	MedDRA (13.0)	Systematic Assessment	EG0001 affected16 at risk EG0010 affected18 at risk EG0020 affected15 at risk EG003

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D006525	Hepatitis, Viral, Human
D014777	Virus Diseases
D018178	Flaviviridae Infections
D012327	RNA Virus Infections
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases

ID	Term
D000069474	Sofosbuvir
C100416	peginterferon alfa-2a
D012254	Ribavirin

ID	Term
D014542	Uridine Monophosphate
D014500	Uracil Nucleotides
D011742	Pyrimidine Nucleotides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D009711	Nucleotides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D012265	Ribonucleotides
D012263	Ribonucleosides
D009705	Nucleosides

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sofosbuvir 100 mg+PEG+RBV	Sofosbuvir 100 mg for 28 days plus PEG+RBV for 48 weeks	1	16	14	16
EG001	Sofosbuvir 200 mg+PEG+RBV	Sofosbuvir 200 mg for 28 days plus PEG+RBV for 48 weeks	0	18	18	18
EG002	Sofosbuvir 400 mg+PEG+RBV	Sofosbuvir 400 mg for 28 days plus PEG+RBV for 48 weeks	3	15	13	15
EG003	Placebo+PEG+RBV	Placebo to match sofosbuvir for 28 days plus PEG+RBV for 48 weeks	1	14	13	14