ATOMIC: Sofosbuvir With Pegylated Interferon and Ribavirin Hepatitis C Virus (HCV) Genotypes 1,4,5,6

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01329978
• Collaborator: (none)
• Enrollment: 332
• Locations: 46
• Arms: 3
• Duration (Months): 17.1
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety, tolerability, and efficacy of sofosbuvir (GS-7977; PSI-7977) administered in combination with pegylated interferon and ribavirin (PEG/RBV) in treatment-naive patients with HCV genotypes 1,4,5,6, or indeterminate genotype.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: Sofosbuvir; Drug: RBV; Drug: PEG	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 332 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The ATOMIC Study: A Multicenter, Open-label, Randomized, Duration Finding Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Pegylated Interferon and Ribavirin in Treatment-Naive Patients With Chronic HCV Infection Genotype 1,4, 5, or 6
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SOF+PEG+RBV 12 weeks Participants were randomized to receive sofosbuvir+PEG+RBV for 12 weeks.	Drug: Sofosbuvir; Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily; Other Names: Sovaldi® GS-7977 PSI-7977 ; Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Other Names: Copegus® ; Drug: PEG; Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Other Names: Pegasys®
Experimental: SOF+PEG+RBV 24 weeks Participants were randomized to receive sofosbuvir+PEG+RBV for 24 weeks.	Drug: Sofosbuvir; Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily; Other Names: Sovaldi® GS-7977 PSI-7977 ; Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Other Names: Copegus® ; Drug: PEG; Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Other Names: Pegasys®
Experimental: SOF+PEG+RBV 12 week/Rerandomization Group Participants were randomized to receive sofosbuvir+PEG+RBV for 12 weeks, then were rerandomized to receive sofosbuvir only or sofosbuvir+RBV for 12 additional weeks.	Drug: Sofosbuvir; Sofosbuvir (SOF) administered as a 400 mg tablet orally once daily; Other Names: Sovaldi® GS-7977 PSI-7977 ; Drug: RBV; Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg); Other Names: Copegus® ; Drug: PEG; Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection; Other Names: Pegasys®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24) [Post-treatment Week 24]

   SVR24 was defined as HCV RNA < the limit of detection (LOD; < 15 IU/mL) 24 weeks after the last dose of study drug.

2. Percentage of Participants Who Experienced Adverse Events [Baseline (Day 1) to post-treatment Day 30]

   Adverse events (AEs) occurring from baseline (Day 1 for all groups) to 30 days following the last dose of study drug were summarized across the participant population. A participant was counted once if they had a qualifying event.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12) [Post-treatment Week 12]

   SVR12 was defined as HCV RNA < LOD 12 weeks after the last dose of study drug.

2. Change in HCV RNA at Week 2 [Baseline (Day 1) to Week 2]

3. Change in HCV RNA at Week 4 [Baseline (Day 1) to Week 4]

4. Change in HCV RNA at Week 8 [Baseline (Day 1) to Week 8]

5. Change in HCV RNA at Week 12 [Baseline (Day 1) to Week 12]

6. Percentage of Participants With HCV RNA < LOD at Week 2 [Week 2]

7. Percentage of Participants With HCV RNA Below < LOD at Week 4 [Week 4]

8. Percentage of Participants With HCV RNA Below < LOD at Week 8 [Week 8]

9. Percentage of Participants With HCV RNA Below < LOD at Week 12 [Week 12]

10. Percentage of Participants With HCV RNA Below < LOD at Week 24 [Week 24]

11. Percentage of Participants With ALT Normalization at Week 12 [Baseline (Day 1) to Week 12]

    ALT normalization was defined as ALT > ULN at baseline and ALT ≤ ULN at Week 12.

12. Percentage of Participants With ALT Normalization at Week 24 [Baseline (Day 1) to Week 24]

    ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Week 24.

13. Percentage of Participants With ALT Normalization at Post-treatment Week 4 [Baseline (Day 1) to Post-treatment Week 4]

    ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Post-treatment Week 4.

14. Percentage of Participants With Virologic Failure During Treatment [Baseline (Day 1) to Week 24]

    Virologic failure was defined as either HCV RNA ≥ 15 IU/mL after having previously had HCV RNA < 15 IU/mL while on treatment, confirmed with 2 consecutive values or last available measurement (ie, breakthrough); > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values or last available measurement (ie, rebound);or HCV RNA persistently ≥ 15 IU/mL through 8 weeks of treatment (ie, nonresponse) Baseline was Day 1 for all groups.

15. Percentage of Participants With Virologic Failure Following Treatment (Viral Relapse). [End of treatment to Post-treatment Week 24]

    Viral relapse was defined as HCV RNA < 15 IU/mL at end of treatment, confirmed with 2 consecutive values or last available measurement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males and females with Chronic Hepatitis C (HCV) Genotype 1,4,5,6, or indeterminate

• Naive to previous HCV treatment

Exclusion Criteria:

• Positive for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab

• History of any other clinically significant chronic liver disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Liver and Digestive Specialist	Montgomery	Alabama	United States	36116
2	Clopton Clinic	Jonesboro	Arkansas	United States	72401
3	Advanced Clinical Research Institute	Anaheim	California	United States	92801
4	Providence Clinical Research	Burbank	California	United States	91505
5	Southern California Liver Centers	Coronado	California	United States	92118
6	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
7	eStudy Site	Oceanside	California	United States	92056
8	Desta Digestive Disease Medical Center	San Diego	California	United States	92114
9	Medical Associates Reseach Group	San Diego	California	United States	92123
10	Kaiser Permanente Hepatology Research	San Diego	California	United States	92154
11	University of Colorado Denver Transplant Center and Hepatology Clinic	Aurora	Colorado	United States	80045
12	South Denver Gastreoenterology	Englewood	Colorado	United States	80110
13	Pointe West Infectious Disease	Bradenton	Florida	United States	34209
14	Avail Clinical Research	Deland	Florida	United States	32720
15	University of Florida College of Medicine	Gainesville	Florida	United States	32610
16	Orlando Immunology Center	Orlando	Florida	United States	32803
17	Internal Medicine Specialists	Orlando	Florida	United States	32806
18	Advanced Research Institute	Trinity	Florida	United States	34655
19	South Florida Center of Gastroenterology	Wellington	Florida	United States	33414
20	Atlanta Gastroenterology Associates	Atlanta	Georgia	United States	30308
21	Gastrointestinal Specialists of Georgia	Marietta	Georgia	United States	30060
22	University of Chicago Medical Center	Chicago	Illinois	United States	60637
23	Investigative Clinical Research	Annapolis	Maryland	United States	21401
24	Clinical Associates Research	Reisterstown	Maryland	United States	21136
25	Beth Israel Deconess Medical Center	Boston	Massachusetts	United States	02215
26	U Mass Memorial Medical Center	Worcester	Massachusetts	United States	01655
27	Henry Ford Health System	Novi	Michigan	United States	48377
28	St. Louis University Gastroenterology and Hepatology Clinical Research	St. Louis	Missouri	United States	63104
29	University of New Mexico Health Science Center	Albuquerque	New Mexico	United States	87131
30	North Shore University Hospital	Manhasset	New York	United States	11303
31	Concorde Medical Group	New York	New York	United States	10016
32	New York Presbyterian Hospital	New York	New York	United States	10021
33	Mt. Sinai Medical Center	New York	New York	United States	10029
34	Asheville Gastroenterology Associates	Asheville	North Carolina	United States	28801
35	Duke University Medical Center	Durham	North Carolina	United States
36	University of Cincinnati	Cincinnati	Ohio	United States	45267
37	Columbia Gastroenterology Associates	Columbia	South Carolina	United States	29204
38	North Texas Research Institute	Arlington	Texas	United States	76012
39	Central Texas Cinical Research	Austin	Texas	United States	78705
40	Baylor University	Dallas	Texas	United States	75246
41	Baylor/ St. Luke's Advanced Liver Therapy	Houston	Texas	United States	77030
42	Alamo Medical Research	San Antonio	Texas	United States	78215
43	Digestive and Liver Disease Specialist	Norfolk	Virginia	United States	23502
44	Virginia Mason Medical Center	Seattle	Washington	United States	98101
45	University Of Puerto Rico	San Juan		Puerto Rico	00935
46	Fundacion de Investigacion de Diego	San Juan		Puerto Rico

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Robert H. Hyland, DPhil, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01329978
• Other Study ID Numbers: P7977-0724
• First Posted: Apr 6, 2011
• Last Update Posted: May 26, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Gilead Sciences: Hepatitis C; HCV; Chronic Hepatitis C
• Additional relevant MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Sofosbuvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled in a total of 42 study sites in the United States. The first participant was screened on 23 March 2011. The last participant observation was on 27 August 2012.
Pre-assignment Detail	589 participants were screened and 332 were randomized and treated, and comprise the Safety Analysis Set.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group	SOF Rerandomization Group	SOF+RBV Rerandomization Group
Arm/Group Description	Participants were randomized to receive sofosbuvir (SOF) 400 mg+pegylated interferon alfa-2a (PEG) 180 µg+ribavirin (RBV) 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.
Period Title: Sofosbuvir+PEG+RBV Treatment Period
STARTED	52	125	155	0	0
COMPLETED	48	112	150	0	0
NOT COMPLETED	4	13	5	0	0
Period Title: Sofosbuvir+PEG+RBV Treatment Period
STARTED	0	0	0	75	75
COMPLETED	0	0	0	70	71
NOT COMPLETED	0	0	0	5	4

Baseline Characteristics

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group	Total
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.	Total of all reporting groups
Overall Participants	52	125	155	332
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51 (9.8)	50 (11.0)	50 (10.8)	50 (10.7)
Sex: Female, Male (Count of Participants)
Female	17 32.7%	52 41.6%	49 31.6%	118 35.5%
Male	35 67.3%	73 58.4%	106 68.4%	214 64.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 19.2%	26 20.8%	31 20%	67 20.2%
Not Hispanic or Latino	42 80.8%	99 79.2%	124 80%	265 79.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
Black	2 3.8%	17 13.6%	16 10.3%	35 10.5%
Not Black	50 96.2%	108 86.4%	139 89.7%	297 89.5%
Hepatitis C Virus (HCV) genotype (participants) [Number]
Genotype 1a	40 76.9%	85 68%	116 74.8%	241 72.6%
Genotype 1b	12 23.1%	24 19.2%	39 25.2%	75 22.6%
Genotype 4	0 0%	11 8.8%	0 0%	11 3.3%
Genotype 6	0 0%	2 1.6%	0 0%	2 0.6%
Genotype 6e	0 0%	2 1.6%	0 0%	2 0.6%
Genotype 6o	0 0%	1 0.8%	0 0%	1 0.3%
HCV RNA (log10 copies/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 copies/mL]	6.5 (0.66)	6.3 (0.73)	6.4 (0.79)	6.4 (0.75)
HCV RNA Category (participants) [Number]
< 800,000 IU/mL	7 13.5%	33 26.4%	28 18.1%	68 20.5%
> 800,000 IU/mL	45 86.5%	92 73.6%	127 81.9%	264 79.5%
Liver Biopsy Fibrosis Score (participants) [Number]
Missing	0 0%	1 0.8%	13 8.4%	14 4.2%
Bridging Fibrosis	7 13.5%	17 13.6%	23 14.8%	47 14.2%
None or Minimal Fibrosis	9 17.3%	14 11.2%	20 12.9%	43 13%
Portal Fibrosis	36 69.2%	93 74.4%	99 63.9%	228 68.7%
Alanine Aminotransferase (ALT) (U/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [U/L]	80.5 (71.61)	83.7 (77.18)	76.4 (55.91)	79.8 (66.98)
ALT Category (participants) [Number]
≤ 1.5 × the upper limit of the normal range (ULN)	37 71.2%	87 69.6%	115 74.2%	239 72%
> 1.5 × ULN	15 28.8%	38 30.4%	40 25.8%	93 28%
IL28b Genotype (participants) [Number]
CC	13 25%	36 28.8%	39 25.2%	88 26.5%
CT	33 63.5%	63 50.4%	88 56.8%	184 55.4%
TT	6 11.5%	26 20.8%	28 18.1%	60 18.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24)
Description	SVR24 was defined as HCV RNA < the limit of detection (LOD; < 15 IU/mL) 24 weeks after the last dose of study drug.
Time Frame	Post-treatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set (participants who were randomized and received at least 1 dose of study drug) with genotype 1 and who had available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group	SOF Rerandomization Group	SOF+RBV Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.
Measure Participants	52	109	155	75	75
Number (95% Confidence Interval) [percentage of participants]	90.4 173.8%	92.7 74.2%	91.0 58.7%	93.3 28.1%	94.7 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SOF+PEG+RBV 12 Weeks, SOF+PEG+RBV 24 Weeks
	Comments	The analyses was stratified by IL28B (CC versus any T allele) and plasma HCV RNA (< 800,000 IU/mL versus ≥ 800,000 IU/mL). Only participants with genotype 1 were included in the comparison due to the fact that participants with genotype 4 and 6 were only enrolled in the SOF+PEG+RBV 24 weeks group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments	The p-value is based on the Cochran-Mantel-Haenszel (CMH) test stratified by randomization stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-1.4
	Confidence Interval	(2-Sided) 95%; -12.2 to 9.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	The difference in proportions and its 95% confidence interval (CI) were calculated based on stratum-adjusted Mantel-Haenszel (MH) proportions.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	SOF+PEG+RBV 12 Weeks, SOF+PEG+RBV 12 Week/Rerandomization Group
	Comments	The analyses was stratified by IL28B (CC versus any T allele) and plasma HCV RNA (< 800,000 IU/mL versus ≥ 800,000 IU/mL).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments	The p-value is based on the CMH test stratified by randomization stratification factors.
	Method	Cochran-Mantel-Haenszel
	Comments	The difference in proportions and its 95% CI were calculated based on stratum-adjusted MH proportions.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -10.8 to 9.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants Who Experienced Adverse Events
Description	Adverse events (AEs) occurring from baseline (Day 1 for all groups) to 30 days following the last dose of study drug were summarized across the participant population. A participant was counted once if they had a qualifying event.
Time Frame	Baseline (Day 1) to post-treatment Day 30

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group	SOF Rerandomization Group	SOF+RBV Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.
Measure Participants	52	125	155	75	75
Any AE	98.1 188.7%	96.8 77.4%	98.7 63.7%	98.7 29.7%	100.0 NaN
Drug-related AE	96.2 185%	94.4 75.5%	97.4 62.8%	98.7 29.7%	97.3 NaN
Grade 3 or higher AE	15.4 29.6%	17.6 14.1%	14.2 9.2%	14.7 4.4%	13.3 NaN
AE leading to drug discontinuation	5.8 11.2%	16.0 12.8%	4.5 2.9%	5.3 1.6%	4.0 NaN
Serious AE	3.8 7.3%	4.8 3.8%	2.6 1.7%	2.7 0.8%	2.7 NaN

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12)
Description	SVR12 was defined as HCV RNA < LOD 12 weeks after the last dose of study drug.
Time Frame	Post-treatment Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group	SOF Rerandomization Group	SOF+RBV Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.
Measure Participants	52	125	155	75	75
Number (95% Confidence Interval) [percentage of participants]	90.4 173.8%	92.0 73.6%	91.0 58.7%	93.3 28.1%	94.7 NaN

4. Secondary Outcome

Title	Change in HCV RNA at Week 2
Time Frame	Baseline (Day 1) to Week 2

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Measure Participants	49	124	153
Mean (Standard Deviation) [log10 IU/mL]	-5.12 (0.660)	-5.07 (0.701)	-5.13 (0.768)

5. Secondary Outcome

Title	Change in HCV RNA at Week 4
Time Frame	Baseline (Day 1) to Week 4

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Measure Participants	50	123	152
Mean (Standard Deviation) [log10 IU/mL]	-5.33 (0.649)	-5.19 (0.733)	-5.24 (0.785)

6. Secondary Outcome

Title	Change in HCV RNA at Week 8
Time Frame	Baseline (Day 1) to Week 8

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Measure Participants	48	118	151
Mean (Standard Deviation) [log10 IU/mL]	-5.34 (0.635)	-5.17 (0.740)	-5.25 (0.789)

7. Secondary Outcome

Title	Change in HCV RNA at Week 12
Time Frame	Baseline (Day 1) to Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Measure Participants	47	113	150
Mean (Standard Deviation) [log10 IU/mL]	-5.36 (0.616)	-5.20 (0.719)	-5.25 (0.791)

8. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LOD at Week 2
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with Available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Measure Participants	51	124	153
Number [percentage of participants]	68.6 131.9%	85.5 68.4%	77.1 49.7%

9. Secondary Outcome

Title	Percentage of Participants With HCV RNA Below < LOD at Week 4
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with Available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Measure Participants	50	123	153
Number [percentage of participants]	98.0 188.5%	100.0 80%	98.7 63.7%

10. Secondary Outcome

Title	Percentage of Participants With HCV RNA Below < LOD at Week 8
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with Available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Measure Participants	48	118	152
Number [percentage of participants]	100.0 192.3%	100.0 80%	99.3 64.1%

11. Secondary Outcome

Title	Percentage of Participants With HCV RNA Below < LOD at Week 12
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with Available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Measure Participants	47	113	150
Number [percentage of participants]	100.0 192.3%	100.0 80%	100.0 64.5%

12. Secondary Outcome

Title	Percentage of Participants With HCV RNA Below < LOD at Week 24
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with Available data were analyzed. No participants in the SOF+PEG+RBV 12 weeks group were analyzed because they received only 12 weeks of treatment.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF Rerandomization Group	SOF+RBV Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.
Measure Participants	0	100	68	74
Number [percentage of participants]	100.0 192.3%	100.0 80%	98.6 63.6%

13. Secondary Outcome

Title	Percentage of Participants With ALT Normalization at Week 12
Description	ALT normalization was defined as ALT > ULN at baseline and ALT ≤ ULN at Week 12.
Time Frame	Baseline (Day 1) to Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with ALT > ULN at baseline and with available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
Measure Participants	23	47	71
Number [percentage of participants]	78.3 150.6%	76.6 61.3%	67.6 43.6%

14. Secondary Outcome

Title	Percentage of Participants With ALT Normalization at Week 24
Description	ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Week 24.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with ALT > ULN at baseline and with available data were analyzed. No participants in the SOF+PEG+RBV 12 weeks group were analyzed because they received only 12 weeks of treatment.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF Rerandomization Group	SOF+RBV Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.
Measure Participants	0	38	35	30
Number [percentage of participants]	78.9 151.7%	94.3 75.4%	100.0 64.5%

15. Secondary Outcome

Title	Percentage of Participants With ALT Normalization at Post-treatment Week 4
Description	ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Post-treatment Week 4.
Time Frame	Baseline (Day 1) to Post-treatment Week 4

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with ALT > ULN at baseline and with available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group	SOF Rerandomization Group	SOF+RBV Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.
Measure Participants	19	47	63	36	26
Number [percentage of participants]	89.5 172.1%	87.2 69.8%	95.2 61.4%	91.7 27.6%	100.0 NaN

16. Secondary Outcome

Title	Percentage of Participants With Virologic Failure During Treatment
Description	Virologic failure was defined as either HCV RNA ≥ 15 IU/mL after having previously had HCV RNA < 15 IU/mL while on treatment, confirmed with 2 consecutive values or last available measurement (ie, breakthrough); > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values or last available measurement (ie, rebound);or HCV RNA persistently ≥ 15 IU/mL through 8 weeks of treatment (ie, nonresponse) Baseline was Day 1 for all groups.
Time Frame	Baseline (Day 1) to Week 24

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group	SOF Rerandomization Group	SOF+RBV Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.
Measure Participants	52	125	155	75	75
Viral breakthrough	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 NaN
Viral rebound	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 NaN
Non-response	0.0 0%	0.0 0%	0.0 0%	0.0 0%	0.0 NaN

17. Secondary Outcome

Title	Percentage of Participants With Virologic Failure Following Treatment (Viral Relapse).
Description	Viral relapse was defined as HCV RNA < 15 IU/mL at end of treatment, confirmed with 2 consecutive values or last available measurement.
Time Frame	End of treatment to Post-treatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis Set with available data were analyzed.

Arm/Group Title	SOF+PEG+RBV 12 Weeks	SOF+PEG+RBV 24 Weeks	SOF+PEG+RBV 12 Week/Rerandomization Group	SOF Rerandomization Group	SOF+RBV Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg monotherapy for 12 additional weeks.	This group includes participants in the SOF+PEG+RBV 12 week/Rerandomization Group who were rerandomized to receive SOF 400 mg+RBV 1000-1200 for 12 additional weeks.
Measure Participants	51	124	153	75	75
Number [percentage of participants]	5.9 11.3%	1.6 1.3%	3.9 2.5%	2.7 0.8%	2.7 NaN

Adverse Events

Time Frame	Baseline (Day 1) to Week 12 or Week 24 (depending upon treatment arm) plus 30 days. Adverse events are counted if they began on or after the date of the first dose and on or before the last dose of study drug plus 30 days.
Adverse Event Reporting Description	As prespecified in the analysis plan, adverse events are reported according to the group to which participants were initially randomized.
Arm/Group Title	SOF+PEG+RBV 12 Weeks		SOF+PEG+RBV 24 Weeks		SOF+PEG+RBV 12 Week/Rerandomization Group
Arm/Group Description	Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks.		Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 24 weeks.		Participants were randomized to receive SOF 400 mg+PEG 180 µg+RBV 1000-1200 mg for 12 weeks, then were rerandomized to receive SOF monotherapy or SOF+RBV for 12 additional weeks.
All Cause Mortality
	SOF+PEG+RBV 12 Weeks		SOF+PEG+RBV 24 Weeks		SOF+PEG+RBV 12 Week/Rerandomization Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	SOF+PEG+RBV 12 Weeks		SOF+PEG+RBV 24 Weeks		SOF+PEG+RBV 12 Week/Rerandomization Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/52 (3.8%)		6/125 (4.8%)		4/155 (2.6%)
Blood and lymphatic system disorders
Anaemia	0/52 (0%)		0/125 (0%)		1/155 (0.6%)
Pancytopenia	0/52 (0%)		1/125 (0.8%)		0/155 (0%)
Cardiac disorders
Arrhythmia	0/52 (0%)		1/125 (0.8%)		0/155 (0%)
Gastrointestinal disorders
Colitis iscaemic	0/52 (0%)		1/125 (0.8%)		0/155 (0%)
General disorders
Chest pain	0/52 (0%)		1/125 (0.8%)		0/155 (0%)
Hepatobiliary disorders
Autoimmune hepatitis	0/52 (0%)		0/125 (0%)		1/155 (0.6%)
Chelocystitis acute	0/52 (0%)		0/125 (0%)		1/155 (0.6%)
Cholelithiasis	0/52 (0%)		0/125 (0%)		1/155 (0.6%)
Infections and infestations
Pyelonephritis	0/52 (0%)		1/125 (0.8%)		0/155 (0%)
Injury, poisoning and procedural complications
Alcoohol poisoning	1/52 (1.9%)		0/125 (0%)		0/155 (0%)
Road traffic accident	1/52 (1.9%)		0/125 (0%)		0/155 (0%)
Musculoskeletal and connective tissue disorders
Costochondritis	0/52 (0%)		1/125 (0.8%)		0/155 (0%)
Surgical and medical procedures
Hip arthroplasty	0/52 (0%)		0/125 (0%)		1/155 (0.6%)
Other (Not Including Serious) Adverse Events
	SOF+PEG+RBV 12 Weeks		SOF+PEG+RBV 24 Weeks		SOF+PEG+RBV 12 Week/Rerandomization Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/52 (98.1%)		121/125 (96.8%)		153/155 (98.7%)
Blood and lymphatic system disorders
Anaemia	7/52 (13.5%)		31/125 (24.8%)		34/155 (21.9%)
Neutropenia	12/52 (23.1%)		25/125 (20%)		22/155 (14.2%)
Thrombocytopenia	5/52 (9.6%)		0/125 (0%)		3/155 (1.9%)
Eye disorders
Vision blurred	6/52 (11.5%)		6/125 (4.8%)		6/155 (3.9%)
Gastrointestinal disorders
Nausea	16/52 (30.8%)		43/125 (34.4%)		51/155 (32.9%)
Diarrhoea	11/52 (21.2%)		23/125 (18.4%)		20/155 (12.9%)
Vomiting	3/52 (5.8%)		17/125 (13.6%)		18/155 (11.6%)
Constipation	3/52 (5.8%)		6/125 (4.8%)		12/155 (7.7%)
Gastrooesophageal reflux disease	3/52 (5.8%)		8/125 (6.4%)		8/155 (5.2%)
Dry mouth	1/52 (1.9%)		8/125 (6.4%)		7/155 (4.5%)
Abdominal pain upper	3/52 (5.8%)		3/125 (2.4%)		7/155 (4.5%)
Abdominal pain	1/52 (1.9%)		7/125 (5.6%)		4/155 (2.6%)
Flatulence	4/52 (7.7%)		2/125 (1.6%)		0/155 (0%)
General disorders
Fatigue	25/52 (48.1%)		63/125 (50.4%)		86/155 (55.5%)
Chills	15/52 (28.8%)		25/125 (20%)		29/155 (18.7%)
Pyrexia	18/52 (34.6%)		15/125 (12%)		26/155 (16.8%)
Pain	9/52 (17.3%)		14/125 (11.2%)		24/155 (15.5%)
Irritability	6/52 (11.5%)		15/125 (12%)		14/155 (9%)
Influenza like illness	3/52 (5.8%)		10/125 (8%)		14/155 (9%)
Injection site erythemia	4/52 (7.7%)		6/125 (4.8%)		10/155 (6.5%)
Injection site reaction	3/52 (5.8%)		5/125 (4%)		9/155 (5.8%)
Asthenia	3/52 (5.8%)		7/125 (5.6%)		4/155 (2.6%)
Injection site rash	0/52 (0%)		4/125 (3.2%)		8/155 (5.2%)
Infections and infestations
Upper respiratory tract infection	1/52 (1.9%)		7/125 (5.6%)		8/155 (5.2%)
Urinary tract infection	0/52 (0%)		6/125 (4.8%)		10/155 (6.5%)
Nasopharyngitis	2/52 (3.8%)		3/125 (2.4%)		9/155 (5.8%)
Sinusitis	1/52 (1.9%)		7/125 (5.6%)		4/155 (2.6%)
Metabolism and nutrition disorders
Decreased appetite	7/52 (13.5%)		17/125 (13.6%)		34/155 (21.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/52 (28.8%)		23/125 (18.4%)		14/155 (9%)
Myalgia	7/52 (13.5%)		17/125 (13.6%)		23/155 (14.8%)
Back pain	3/52 (5.8%)		11/125 (8.8%)		12/155 (7.7%)
Muscle spasms	5/52 (9.6%)		12/125 (9.6%)		5/155 (3.2%)
Pain in extremity	3/52 (5.8%)		6/125 (4.8%)		8/155 (5.2%)
Musculoskeletal pain	5/52 (9.6%)		6/125 (4.8%)		5/155 (3.2%)
Nervous system disorders
Headache	14/52 (26.9%)		38/125 (30.4%)		65/155 (41.9%)
Dizziness	8/52 (15.4%)		19/125 (15.2%)		21/155 (13.5%)
Dysgeusia	3/52 (5.8%)		3/125 (2.4%)		10/155 (6.5%)
Disturbance in attention	1/52 (1.9%)		4/125 (3.2%)		9/155 (5.8%)
Psychiatric disorders
Insomnia	12/52 (23.1%)		28/125 (22.4%)		36/155 (23.2%)
Anxiety	4/52 (7.7%)		17/125 (13.6%)		22/155 (14.2%)
Depression	4/52 (7.7%)		17/125 (13.6%)		19/155 (12.3%)
Affect lability	4/52 (7.7%)		4/125 (3.2%)		8/155 (5.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	8/52 (15.4%)		18/125 (14.4%)		21/155 (13.5%)
Cough	5/52 (9.6%)		11/125 (8.8%)		22/155 (14.2%)
Oropharyngeal pain	3/52 (5.8%)		5/125 (4%)		6/155 (3.9%)
Skin and subcutaneous tissue disorders
Rash	7/52 (13.5%)		26/125 (20.8%)		39/155 (25.2%)
Pruritus	5/52 (9.6%)		18/125 (14.4%)		16/155 (10.3%)
Alopecia	4/52 (7.7%)		15/125 (12%)		10/155 (6.5%)
Hyperhidrosis	3/52 (5.8%)		9/125 (7.2%)		7/155 (4.5%)
Dry skin	3/52 (5.8%)		8/125 (6.4%)		5/155 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years