TOPAZ-II: A Study to Evaluate Long-term Outcomes Following Treatment With ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02167945
• Collaborator: (none)
• Enrollment: 615
• Locations: 48
• Arm: 1
• Actual Duration (Months): 83
• Patients Per Site: 12.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the effect of treatment with ABT-450 co-formulated with ritonavir and ABT-267 (ABT-450/r/ABT-267) and ABT-333; 3-DAA regimen, with or without ribavirin (RBV) in adults with chronic hepatitis C virus genotype 1 (HCV GT1) infection.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Virus (HCV) Infection Genotype 1	Drug: ABT-450/r/ABT-267; Drug: ABT-333; Drug: Ribavirin (RBV)	Phase 3

Detailed Description

This study (TOPAZ-II; M14-222), was a Phase 3b, open-label, multicenter study conducted in the United States which, together with its companion study TOPAZ-I (M14-423; NCT02219490) conducted outside of the United States, was designed with the primary objective of assessing the effect of treatment response on long-term clinical outcomes in adults with chronic HCV GT1 infection with or without compensated cirrhosis, who were either treatment-naïve or interferon/ribavirin (IFN/RBV) treatment- experienced. In both studies, participants were treated with the 3-DAA regimen with or without RBV. This study consisted of a screening period of up to 42 days, a treatment period of either 12 weeks for HCV GT1a-infected subjects without cirrhosis and for HCV GT1b-infected subjects without cirrhosis or with compensated cirrhosis or 24 weeks for GT1a-infected participants with compensated cirrhosis, and a 260-week post-treatment period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 615 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study to Evaluate Long-term Outcomes With ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection (TOPAZ-II)
• Actual Study Start Date: Jun 12, 2014
• Actual Primary Completion Date: May 13, 2021
• Actual Study Completion Date: May 13, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV) Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks.

Drug: ABT-450/r/ABT-267; Tablet for oral use; Other Names: ABT-450 also known as paritaprevir ABT-267 also known as ombitasvir Paritaprevir/ritonavir/ombitasvir also known as Viekirax ; Drug: ABT-333; Tablet for oral use; Other Names: ABT-333 also known as dasabuvir ABT-333 also known as Exviera ; Drug: Ribavirin (RBV); Ribavirin was provided as 200 mg tablets, and dosed based on weight, 1000 to 1200 mg divided twice daily per local label. For example, for participants weighing < 75 kg, RBV may have been taken orally as 2 tablets in the morning and 3 tablets in the evening which corresponds to a 1000 mg total daily dose. For participants weighing ≥ 75 kg, RBV may have been taken orally as 3 tablets in the morning and 3 tablets in the evening which corresponds to a 1200 mg total daily dose.

Outcome Measures

Primary Outcome Measures

1. All-Cause Death: Time to Event [At Post-Treatment Weeks 52, 104, 156, 208, and 260]

   Time to all-cause death was defined as the number of days from the first day of study drug dosing for the participant to the date of death. All deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not die, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of all-cause death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

2. Liver-Related Death: Time to Event [At Post-Treatment Weeks 52, 104, 156, 208, and 260]

   Time to liver-related death was defined as number of days from the 1st day of study drug dosing for the participant to date of liver-related death. All liver-related deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver-related death. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver-related death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

3. Liver Decompensation: Time to Event [At Post-Treatment Weeks 52, 104, 156, 208, and 260]

   Time to liver decompensation was defined as number of days from the 1st day of study drug dosing for the participant to the date of liver decompensation. All liver decompensation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver decompensation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver decompensation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

4. Liver Transplantation: Time to Event [At Post-Treatment Weeks 52, 104, 156, 208, and 260]

   Time to liver transplantation was defined as number of days from the 1st day of study drug dosing for the participant to date of liver transplantation. All liver transplantation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver transplantation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver transplantation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

5. Hepatocellular Carcinoma: Time to Event [At Post-Treatment Weeks 52, 104, 156, 208, and 260]

   Time to hepatocellular carcinoma was defined as number of days from the 1st day of study drug dosing for the participant to date of hepatocellular carcinoma. All hepatocellular carcinoma was to be included, whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For those with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for hepatocellular carcinoma. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of hepatocellular carcinoma included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).

6. All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event [At Post-Treatment Weeks 52, 104, 156, 208, and 260]

   Time to the composite of clinical outcomes is the time to the first occurrence of all-cause death, liver-related death, liver decompensation, liver transplantation, or hepatocellular carcinoma. All first occurrences were to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not experience any of these events, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. Pre-specified analysis included pooled data from this study and from TOPAZ-I; NCT02219490.

Secondary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [12 weeks after the last actual dose of study drug]

   SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.

2. Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Physical Component Summary (PCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24 [From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24]

   The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of 4 weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health. Positive numbers indicate improvement from baseline.

3. Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Mental Component Summary (MCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24 [From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24]

   The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of 4 weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health. Positive numbers indicate improvement from baseline.

4. Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Post-Treatment Week 12 and Post-Treatment Week 24 [From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24]

   The FACIT-F is a symptom specific instrument with a focus on measuring fatigue in a variety of chronic diseases or health conditions. It was originally developed from interviews with oncology patients and clinical experts to assess anemia-associated fatigue. Its 13-item-version assesses peripheral, central, or mixed fatigue with a recall period of 7 days and yields a summed total score ranging between 0 and 52. Higher FACIT-F scores indicate a lesser degree of fatigue. Positive numbers indicate improvement from baseline.

5. Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets [Up to Treatment Week 24]

   Treatment compliance was calculated as the percentage of tablets taken (presumed as [tablets dispensed-tablets returned]) relative to the total tablets, respectively, expected to be taken. Study drug interruptions due to an adverse event or other planned interruptions recorded on the electronic case report form (eCRF) were to be subtracted from the duration. For compliance to ribavirin (RBV), RBV dose modifications due to adverse events, toxicity management, or weight changes as recorded on the RBV Dose Modifications eCRF were to be used to modify the total number of tablets that should have been taken. A participant is considered to be compliant if the percentage is between 80% and 120%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Females must be post-menopausal for more than 2 years or surgically sterile or practicing specific forms of birth control

2. Chronic hepatitis C, genotype 1-infection (HCV RNA level greater than 1,000 IU/mL at screening)

3. HCV genotype 1 infection per screening laboratory result

Exclusion Criteria:

1. Use of contraindicated medications within 2 weeks of dosing

2. Abnormal laboratory tests

3. Positive hepatitis B surface antigen and anti-Human Immunodeficiency Virus Antibody

4. History of solid organ transplant, clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation

5. Presence of hepatocellular carcinoma at screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Josephs Hospital and Med Center /ID# 127800	Phoenix	Arizona	United States	85013
2	Franco Felizarta, Md /Id# 126569	Bakersfield	California	United States	93301
3	Ruane Clinical Research Group /ID# 126577	Los Angeles	California	United States	90036
4	California Pacific Medical Center /ID# 128681	San Francisco	California	United States	94115
5	Univ of Colorado Cancer Center /ID# 126568	Aurora	Colorado	United States	80045
6	Medstar Health Research Institute /ID# 128683	Washington	District of Columbia	United States	20010
7	Bach and Godofsky Infec Dis /ID# 128685	Bradenton	Florida	United States	34209
8	University of Florida - Archer /ID# 127787	Gainesville	Florida	United States	32610
9	Encore Borland-Groover Clinical Research /Id# 127781	Jacksonville	Florida	United States	32256
10	University of Miami /ID# 127622	Miami	Florida	United States	33136
11	South Florida Ctr Gastro, P.A. /ID# 126567	Wellington	Florida	United States	33414
12	Atlanta Gastro Assoc /ID# 126571	Atlanta	Georgia	United States	30342
13	Northwestern University Feinberg School of Medicine /ID# 128684	Chicago	Illinois	United States	60611-2927
14	The University of Chicago Medical Center /ID# 126576	Chicago	Illinois	United States	60637-1443
15	Duplicate_Indiana University Health /ID# 126573	Indianapolis	Indiana	United States	46202
16	Tulane University /ID# 127779	New Orleans	Louisiana	United States	70112-2699
17	Louisana Research Center, LLC /ID# 126561	Shreveport	Louisiana	United States	71105-6800
18	Johns Hopkins University /ID# 127791	Baltimore	Maryland	United States	21287
19	Digestive Disease Associates - Catonsville /ID# 127624	Catonsville	Maryland	United States	21228
20	Beth Israel Deaconess Medical Center /ID# 126560	Boston	Massachusetts	United States	02215-5400
21	Henry Ford Health System /ID# 127783	Detroit	Michigan	United States	48202
22	Minnesota Gastroenterology PA /ID# 126579	Plymouth	Minnesota	United States	55446
23	St. Louis University /ID# 126564	Saint Louis	Missouri	United States	63104
24	AGA Clinical Research Associates, LLC /ID# 126578	Egg Harbor Township	New Jersey	United States	08234
25	Rutgers New Jersey School of Medicine /ID# 128686	Newark	New Jersey	United States	07103
26	University of New Mexico /ID# 128859	Albuquerque	New Mexico	United States	87102-4517
27	Southwest Care Center /ID# 127784	Santa Fe	New Mexico	United States	87505
28	North Shore University Hospital /ID# 126565	New Hyde Park	New York	United States	11040
29	The Mount Sinai Hospital /ID# 128682	New York	New York	United States	10029
30	Columbia Univ Medical Center /ID# 126566	New York	New York	United States	10032-3725
31	Columbia Univ Medical Center /ID# 127621	New York	New York	United States	10032-3725
32	Premier Medical Group - GI Division /ID# 127793	Poughkeepsie	New York	United States	12601
33	Univ Rochester Med Ctr /ID# 127655	Rochester	New York	United States	14642
34	Atrium Health Carolinas Medical Center /ID# 127632	Charlotte	North Carolina	United States	28203
35	Carolinas Center For Liver Dis /ID# 127788	Statesville	North Carolina	United States	28677
36	University of Cincinnati Physicians Company, LLC /ID# 127790	Cincinnati	Ohio	United States	45267-2827
37	Options Health Research, LLC /ID# 127630	Tulsa	Oklahoma	United States	74104
38	University Gastroenterology /ID# 127789	Providence	Rhode Island	United States	02905
39	Gastro One /ID# 127792	Germantown	Tennessee	United States	38138
40	Inquest Clinical Research /ID# 126574	Baytown	Texas	United States	77521-2415
41	Cure C Consortium /ID# 126570	Houston	Texas	United States	77004
42	Liver Associates of Texas, P.A /ID# 126563	Houston	Texas	United States	77030-2783
43	Austin Institute for Clinical Research /ID# 126562	Pflugerville	Texas	United States	78660
44	TX Liver Inst, Americ Res Corp /ID# 127623	San Antonio	Texas	United States	78215
45	Clinical Research Ctrs America /ID# 127780	Murray	Utah	United States	84123
46	Virginia Mason - Seattle Orthapedics /ID# 130288	Seattle	Washington	United States	98101
47	University of Washington /ID# 127785	Seattle	Washington	United States	98109
48	Dean Clinic /ID# 126575	Madison	Wisconsin	United States	53715

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: ABBVIE INC., AbbVie

Study Documents (Full-Text)

• Study Protocol - Dec 19, 2014
• Statistical Analysis Plan - Jul 7, 2015

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02167945
• Other Study ID Numbers: M14-222
• First Posted: Jun 19, 2014
• Last Update Posted: Jul 19, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by AbbVie: Hepatitis C Genotype 1; Compensated Cirrhosis; Cirrhosis; Naïve; Hepatitis C; Hepatitis C Virus; Treatment-Experienced; Relapser; Null responder; Non responder
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin

Study Results

Participant Flow

Pre-assignment Detail	Safety population: All participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug

Arm/Group Title	ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV)
Arm/Group Description	Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks.
Period Title: Overall Study
STARTED	615
COMPLETED	366
NOT COMPLETED	249

Baseline Characteristics

Arm/Group Title	ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV)
Arm/Group Description	Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks.
Overall Participants	615
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.5 (10.84)
Sex: Female, Male (Count of Participants)
Female	243 39.5%
Male	372 60.5%
Race/Ethnicity, Customized (Count of Participants)
White	520 84.6%
Black or African American	84 13.7%
Asian	4 0.7%
American Indian or Alaska Native	4 0.7%
Native Hawaiian or Other Pacific Islander	0 0%
Multiple	3 0.5%
HCV Genotype 1 Subtype (Count of Participants)
GT1b without cirrhosis	141 22.9%
GT1b with compensated cirrhosis	22 3.6%
GT1 Non-b without cirrhosis	359 58.4%
GT1 Non-b with compensated cirrhosis	93 15.1%
Prior HCV Treatment History (Count of Participants)
Treatment Naïve	437 71.1%
Treatment Experienced	178 28.9%

Outcome Measures

1. Primary Outcome

Title	All-Cause Death: Time to Event
Description	Time to all-cause death was defined as the number of days from the first day of study drug dosing for the participant to the date of death. All deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not die, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of all-cause death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
Time Frame	At Post-Treatment Weeks 52, 104, 156, 208, and 260

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug

Arm/Group Title	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12	Participants in Studies M14-222 and M14-423 Who Achieved SVR12
Arm/Group Description	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Measure Participants	77	2134
Kaplan-Meier estimate at PT Week 52	8.3 1.3%	0.1 NaN
Kaplan-Meier estimate at PT Week 104	8.3 1.3%	0.7 NaN
Kaplan-Meier estimate at PT Week 156	8.3 1.3%	1.2 NaN
Kaplan-Meier estimate at PT Week 208	8.3 1.3%	1.5 NaN
Kaplan-Meier estimate at PT Week 260	8.3 1.3%	2.0 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log-rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard Ratio
	Estimated Value	0.126
	Confidence Interval	(2-Sided) 95%; 0.044 to 0.358
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value represents the hazard ratio for developing the event in the group of participants in studies M14-222 and M14-423 who achieved SVR12 compared to the group of participants in studies M14-222 and M14-423 who didn't achieve SVR12.

2. Primary Outcome

Title	Liver-Related Death: Time to Event
Description	Time to liver-related death was defined as number of days from the 1st day of study drug dosing for the participant to date of liver-related death. All liver-related deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver-related death. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver-related death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
Time Frame	At Post-Treatment Weeks 52, 104, 156, 208, and 260

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug

Arm/Group Title	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12	Participants in Studies M14-222 and M14-423 Who Achieved SVR12
Arm/Group Description	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Measure Participants	77	2134
Kaplan-Meier estimate at PT Week 52	1.4 0.2%	0 NaN
Kaplan-Meier estimate at PT Week 104	1.4 0.2%	0 NaN
Kaplan-Meier estimate at PT Week 156	1.4 0.2%	0.1 NaN
Kaplan-Meier estimate at PT Week 208	1.4 0.2%	0.1 NaN
Kaplan-Meier estimate at PT Week 260	1.4 0.2%	0.1 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log-rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard Ratio
	Estimated Value	0.031
	Confidence Interval	(2-Sided) 95%; 0.003 to 0.380
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value represents the hazard ratio for developing the event in the group of participants in studies M14-222 and M14-423 who achieved SVR12 compared to the group of participants in studies M14-222 and M14-423 who didn't achieve SVR12.

3. Primary Outcome

Title	Liver Decompensation: Time to Event
Description	Time to liver decompensation was defined as number of days from the 1st day of study drug dosing for the participant to the date of liver decompensation. All liver decompensation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver decompensation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver decompensation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
Time Frame	At Post-Treatment Weeks 52, 104, 156, 208, and 260

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug

Arm/Group Title	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12	Participants in Studies M14-222 and M14-423 Who Achieved SVR12
Arm/Group Description	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Measure Participants	77	2134
Kaplan-Meier estimate at PT Week 52	4.5 0.7%	0.2 NaN
Kaplan-Meier estimate at PT Week 104	4.5 0.7%	0.2 NaN
Kaplan-Meier estimate at PT Week 156	4.5 0.7%	0.3 NaN
Kaplan-Meier estimate at PT Week 208	4.5 0.7%	0.3 NaN
Kaplan-Meier estimate at PT Week 260	4.5 0.7%	0.5 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log-rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard Ratio
	Estimated Value	0.038
	Confidence Interval	(2-Sided) 95%; 0.009 to 0.156
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value represents the hazard ratio for developing the event in the group of participants in studies M14-222 and M14-423 who achieved SVR12 compared to the group of participants in studies M14-222 and M14-423 who didn't achieve SVR12.

4. Primary Outcome

Title	Liver Transplantation: Time to Event
Description	Time to liver transplantation was defined as number of days from the 1st day of study drug dosing for the participant to date of liver transplantation. All liver transplantation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver transplantation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver transplantation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
Time Frame	At Post-Treatment Weeks 52, 104, 156, 208, and 260

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug

Arm/Group Title	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12	Participants in Studies M14-222 and M14-423 Who Achieved SVR12
Arm/Group Description	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Measure Participants	77	2134
Kaplan-Meier estimate at PT Week 52	0 0%	0 NaN
Kaplan-Meier estimate at PT Week 104	0 0%	0 NaN
Kaplan-Meier estimate at PT Week 156	0 0%	0.1 NaN
Kaplan-Meier estimate at PT Week 208	0 0%	0.1 NaN
Kaplan-Meier estimate at PT Week 260	0 0%	0.2 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.860
	Comments
	Method	Log-rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.997
	Comments	The Hazard Ratio for experiencing the event in the group of participants in studies M14-222 and M14-423 who achieved SVR12 compared to those who did not achieve SVR12 is infinite and the CI is not bounded due to zero events in one of the groups.
	Method	Cox proportional hazards model
	Comments

5. Primary Outcome

Title	Hepatocellular Carcinoma: Time to Event
Description	Time to hepatocellular carcinoma was defined as number of days from the 1st day of study drug dosing for the participant to date of hepatocellular carcinoma. All hepatocellular carcinoma was to be included, whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For those with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for hepatocellular carcinoma. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of hepatocellular carcinoma included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
Time Frame	At Post-Treatment Weeks 52, 104, 156, 208, and 260

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug

Arm/Group Title	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12	Participants in Studies M14-222 and M14-423 Who Achieved SVR12
Arm/Group Description	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Measure Participants	77	2134
Kaplan-Meier estimate at PT Week 52	0 0%	0.2 NaN
Kaplan-Meier estimate at PT Week 104	0 0%	0.4 NaN
Kaplan-Meier estimate at PT Week 156	0 0%	0.5 NaN
Kaplan-Meier estimate at PT Week 208	0 0%	0.6 NaN
Kaplan-Meier estimate at PT Week 260	0 0%	0.9 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.608
	Comments
	Method	Log-rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.992
	Comments	The Hazard Ratio for experiencing the event in the group of participants in studies M14-222 and M14-423 who achieved SVR12 compared to those who did not achieve SVR12 is infinite and the CI is not bounded due to zero events in one of the groups.
	Method	Cox proportional hazards model
	Comments

6. Primary Outcome

Title	All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event
Description	Time to the composite of clinical outcomes is the time to the first occurrence of all-cause death, liver-related death, liver decompensation, liver transplantation, or hepatocellular carcinoma. All first occurrences were to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not experience any of these events, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. Pre-specified analysis included pooled data from this study and from TOPAZ-I; NCT02219490.
Time Frame	At Post-Treatment Weeks 52, 104, 156, 208, and 260

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug

Arm/Group Title	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12	Participants in Studies M14-222 and M14-423 Who Achieved SVR12
Arm/Group Description	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Measure Participants	77	2134
Kaplan-Meier estimate at PT Week 52	11.4 1.9%	0.5 NaN
Kaplan-Meier estimate at PT Week 104	11.4 1.9%	1.2 NaN
Kaplan-Meier estimate at PT Week 156	11.4 1.9%	1.9 NaN
Kaplan-Meier estimate at PT Week 208	11.4 1.9%	2.3 NaN
Kaplan-Meier estimate at PT Week 260	11.4 1.9%	3.2 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log-rank test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cox proportional hazards model
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard Ratio
	Estimated Value	0.133
	Confidence Interval	(2-Sided) 95%; 0.057 to 0.313
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value represents the hazard ratio for developing the event in the group of participants in studies M14-222 and M14-423 who achieved SVR12 compared to the group of participants in studies M14-222 and M14-423 who didn't achieve SVR12.

7. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
Description	SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Time Frame	12 weeks after the last actual dose of study drug

Outcome Measure Data

Analysis Population Description

ITT-II population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug. Flanking imputation, where applicable, was used to impute missing data. After applying flanking imputation, if there was no value in the window but there was an HCV RNA value from a local laboratory present, then it was to be imputed into the SVR window. Otherwise, participants with missing data were counted as failures.

Arm/Group Title	ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV)
Arm/Group Description	Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks.
Measure Participants	615
Number (95% Confidence Interval) [percentage of participants]	95.3 15.5%

8. Secondary Outcome

Title	Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Physical Component Summary (PCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24
Description	The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of 4 weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health. Positive numbers indicate improvement from baseline.
Time Frame	From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24

Outcome Measure Data

Analysis Population Description

ITT-II population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug and had both baseline and post-treatment data

Arm/Group Title	Baseline Fibrosis Stage F0-F1	Baseline Fibrosis Stage F2	Baseline Fibrosis Stage F3	Baseline Fibrosis Stage F4
Arm/Group Description	Participants in study M14-222 with a baseline fibrosis stage of F0 or F1	Participants in study M14-222 with a baseline fibrosis stage of F2	Participants in study M14-222 with a baseline fibrosis stage of F3	Participants in study M14-222 with a baseline fibrosis stage of F4
Measure Participants	291	85	104	106
At Post-treatment Week 12	1.2 (6.33)	0.0 (6.32)	1.8 (7.80)	1.4 (7.54)
At Post-treatment Week 24	1.1 (6.86)	0.5 (7.47)	2.3 (8.11)	1.8 (7.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	F0-F1 vs F2 at Post-treatment Week 12 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.75
	Confidence Interval	(2-Sided) 95%; -3.30 to -0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.79
	Estimation Comments	F2 - F0-F1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F3
	Comments	F0-F1 vs F3 at Post-treatment Week 12 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.472
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.53
	Confidence Interval	(2-Sided) 95%; -1.97 to 0.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.74
	Estimation Comments	F3 - F0-F1

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F4
	Comments	F0-F1 vs F4 at Post-treatment Week 12 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.159
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.03
	Confidence Interval	(2-Sided) 95%; -2.47 to 0.40
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.73
	Estimation Comments	F4 - F0-F1

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	F0-F1 vs F2 at Post-treatment Week 24 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.125
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.30
	Confidence Interval	(2-Sided) 95%; -2.95 to 0.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.84
	Estimation Comments	F2 - F0-F1

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F3
	Comments	F0-F1 vs F3 at Post-treatment Week 24 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.756
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -1.78 to 1.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.78
	Estimation Comments	F3 - F0-F1

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F4
	Comments	F0-F1 vs F4 at Post-treatment Week 24 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.315
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.79
	Confidence Interval	(2-Sided) 95%; -2.32 to 0.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.78
	Estimation Comments	F4 - F0-F1

9. Secondary Outcome

Title	Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Mental Component Summary (MCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24
Description	The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of 4 weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health. Positive numbers indicate improvement from baseline.
Time Frame	From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24

Outcome Measure Data

Analysis Population Description

ITT-II population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug and had both baseline and post-treatment data

Arm/Group Title	Baseline Fibrosis Stage F0-F1	Baseline Fibrosis Stage F2	Baseline Fibrosis Stage F3	Baseline Fibrosis Stage F4
Arm/Group Description	Participants in study M14-222 with a baseline fibrosis stage of F0 or F1	Participants in study M14-222 with a baseline fibrosis stage of F2	Participants in study M14-222 with a baseline fibrosis stage of F3	Participants in study M14-222 with a baseline fibrosis stage of F4
Measure Participants	291	85	104	106
At Post-treatment Week 12	2.7 (9.77)	1.0 (9.05)	0.9 (9.64)	0.3 (10.62)
At Post-treatment Week 24	3.2 (9.85)	1.9 (7.28)	1.5 (10.73)	0.4 (10.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	F0-F1 vs F2 at Post-treatment Week 12 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.216
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.28
	Confidence Interval	(2-Sided) 95%; -3.30 to 0.75
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.03
	Estimation Comments	F2 - F0-F1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F3
	Comments	F0-F1 vs F3 at Post-treatment Week 12 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.074
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.70
	Confidence Interval	(2-Sided) 95%; -3.58 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.95
	Estimation Comments	F3 - F0-F1

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F4
	Comments	F0-F1 vs F4 at Post-treatment Week 12 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.056
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.81
	Confidence Interval	(2-Sided) 95%; -3.67 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.95
	Estimation Comments	F4 - F0-F1

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	F0-F1 vs F2 at Post-treatment Week 24 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.411
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.84
	Confidence Interval	(2-Sided) 95%; -2.84 to 1.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.02
	Estimation Comments	F2 - F0-F1

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F3
	Comments	F0-F1 vs F3 at Post-treatment Week 24 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.065
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.72
	Confidence Interval	(2-Sided) 95%; -3.55 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.93
	Estimation Comments	F3 - F0-F1

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F4
	Comments	F0-F1 vs F4 at Post-treatment Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.08
	Confidence Interval	(2-Sided) 95%; -3.91 to -0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.93
	Estimation Comments	F4 - F0-F1

10. Secondary Outcome

Title	Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Post-Treatment Week 12 and Post-Treatment Week 24
Description	The FACIT-F is a symptom specific instrument with a focus on measuring fatigue in a variety of chronic diseases or health conditions. It was originally developed from interviews with oncology patients and clinical experts to assess anemia-associated fatigue. Its 13-item-version assesses peripheral, central, or mixed fatigue with a recall period of 7 days and yields a summed total score ranging between 0 and 52. Higher FACIT-F scores indicate a lesser degree of fatigue. Positive numbers indicate improvement from baseline.
Time Frame	From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24

Outcome Measure Data

Analysis Population Description

ITT-II population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug who had both baseline and post-treatment data.

Arm/Group Title	Baseline Fibrosis Stage F0-F1	Baseline Fibrosis Stage F2	Baseline Fibrosis Stage F3	Baseline Fibrosis Stage F4
Arm/Group Description	Participants in study M14-222 with a baseline fibrosis stage of F0 or F1	Participants in study M14-222 with a baseline fibrosis stage of F2	Participants in study M14-222 with a baseline fibrosis stage of F3	Participants in study M14-222 with a baseline fibrosis stage of F4
Measure Participants	292	86	103	105
At Post-treatment Week 12	3.9 (9.66)	2.0 (9.12)	2.0 (8.63)	3.0 (9.57)
At Post-treatment Week 24	3.9 (10.46)	3.1 (6.85)	2.3 (9.27)	2.6 (10.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	F0-F1 vs F2 at Post-treatment Week 12 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes (PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95%; -3.86 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.95
	Estimation Comments	F2 - F0-F1

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F3
	Comments	F0-F1 vs F3 at Post-treatment Week 12 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.15
	Confidence Interval	(2-Sided) 95%; -3.88 to -0.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.88
	Estimation Comments	F3 - F0-F1

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F4
	Comments	F0-F1 vs F4 at Post-treatment Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.74
	Confidence Interval	(2-Sided) 95%; -3.46 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.88
	Estimation Comments	F4 - F0-F1

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Participants in Studies M14-222 and M14-423 Who Achieved SVR12
	Comments	F0-F1 vs F2 at Post-treatment Week 24 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.466
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.72
	Confidence Interval	(2-Sided) 95%; -2.67 to 1.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.99
	Estimation Comments	F2 - F0-F1

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F3
	Comments	F0-F1 vs F3 at Post-treatment Week 24 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.035
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.91
	Confidence Interval	(2-Sided) 95%; -3.70 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.91
	Estimation Comments	F3 - F0-F1

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12, Baseline Fibrosis Stage F4
	Comments	F0-F1 vs F4 at Post-treatment Week 24 The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.22
	Confidence Interval	(2-Sided) 95%; -4.01 to -0.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.91
	Estimation Comments	F4 - F0-F1

11. Secondary Outcome

Title	Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets
Description	Treatment compliance was calculated as the percentage of tablets taken (presumed as [tablets dispensed-tablets returned]) relative to the total tablets, respectively, expected to be taken. Study drug interruptions due to an adverse event or other planned interruptions recorded on the electronic case report form (eCRF) were to be subtracted from the duration. For compliance to ribavirin (RBV), RBV dose modifications due to adverse events, toxicity management, or weight changes as recorded on the RBV Dose Modifications eCRF were to be used to modify the total number of tablets that should have been taken. A participant is considered to be compliant if the percentage is between 80% and 120%.
Time Frame	Up to Treatment Week 24

Outcome Measure Data

Analysis Population Description

Safety population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug with available data

Arm/Group Title	ABT-450/r/ABT-267 Plus ABT-333	Weight-based Ribavirin (RBV)
Arm/Group Description	Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen for 24 weeks.	Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received weight-based RBV per local label for 24 weeks. Ribavirin was provided as 200 mg tablets, and dosed based on weight, 1000 to 1200 mg divided twice daily per local label. For example, for participants weighing < 75 kg, RBV may have been taken orally as 2 tablets in the morning and 3 tablets in the evening which corresponds to a 1000 mg total daily dose. For participants weighing ≥ 75 kg, RBV may have been taken orally as 3 tablets in the morning and 3 tablets in the evening which corresponds to a 1200 mg total daily dose.
Measure Participants	567	408
Mean (Standard Deviation) [percentage of tablets taken]	100.22 (22.88)	99.86 (12.40)

Adverse Events

Time Frame	All-cause mortality is reported from enrollment to the end of study, up to five years of follow-up. Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after the last study drug administration, up to 213 days. After Post-Treatment Week 4 until the end of the study, only SAE of death was to be collected.
Adverse Event Reporting Description	All-cause mortality and adverse events: all participants in this study (M14-222; TOPAZ-II) who received at least one dose of study drug
Arm/Group Title	ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV)
Arm/Group Description	Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks.
All Cause Mortality
	ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV)
	Affected / at Risk (%)	# Events
Total	19/615 (3.1%)
Serious Adverse Events
	ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV)
	Affected / at Risk (%)	# Events
Total	25/615 (4.1%)
Cardiac disorders
CORONARY ARTERY DISEASE	1/615 (0.2%)	1
PERICARDITIS	1/615 (0.2%)	1
Endocrine disorders
HYPERADRENOCORTICISM	1/615 (0.2%)	1
Gastrointestinal disorders
INGUINAL HERNIA	1/615 (0.2%)	1
SMALL INTESTINAL OBSTRUCTION	1/615 (0.2%)	1
General disorders
CHEST PAIN	1/615 (0.2%)	1
Hepatobiliary disorders
CHOLECYSTITIS	1/615 (0.2%)	1
Immune system disorders
ALLERGIC OEDEMA	1/615 (0.2%)	1
Infections and infestations
BRONCHITIS	1/615 (0.2%)	1
PERITONITIS	1/615 (0.2%)	1
PNEUMONIA	1/615 (0.2%)	1
PNEUMONIA PNEUMOCOCCAL	1/615 (0.2%)	1
Injury, poisoning and procedural complications
ALCOHOL POISONING	1/615 (0.2%)	1
ANKLE FRACTURE	1/615 (0.2%)	1
MULTIPLE FRACTURES	1/615 (0.2%)	1
OVERDOSE	1/615 (0.2%)	1
RIB FRACTURE	1/615 (0.2%)	1
SPINAL FRACTURE	1/615 (0.2%)	1
UPPER LIMB FRACTURE	1/615 (0.2%)	1
Metabolism and nutrition disorders
DIABETES MELLITUS	1/615 (0.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
HEPATOCELLULAR CARCINOMA	1/615 (0.2%)	1
LUNG ADENOCARCINOMA	1/615 (0.2%)	1
PANCREATIC CARCINOMA METASTATIC	2/615 (0.3%)	2
Psychiatric disorders
ALCOHOL WITHDRAWAL SYNDROME	1/615 (0.2%)	1
MENTAL STATUS CHANGES	2/615 (0.3%)	2
SCHIZOAFFECTIVE DISORDER	1/615 (0.2%)	1
SUICIDE ATTEMPT	1/615 (0.2%)	1
Renal and urinary disorders
ACUTE KIDNEY INJURY	1/615 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
BRONCHOSPASM	1/615 (0.2%)	1
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	1/615 (0.2%)	1
PLEURISY	1/615 (0.2%)	1
Vascular disorders
HYPOTENSION	1/615 (0.2%)	1
Other (Not Including Serious) Adverse Events
	ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV)
	Affected / at Risk (%)	# Events
Total	381/615 (62%)
Blood and lymphatic system disorders
ANAEMIA	32/615 (5.2%)	32
Gastrointestinal disorders
DIARRHOEA	54/615 (8.8%)	59
NAUSEA	99/615 (16.1%)	104
VOMITING	31/615 (5%)	32
General disorders
FATIGUE	198/615 (32.2%)	209
Nervous system disorders
DIZZINESS	37/615 (6%)	38
HEADACHE	98/615 (15.9%)	101
Psychiatric disorders
INSOMNIA	78/615 (12.7%)	80
Respiratory, thoracic and mediastinal disorders
COUGH	35/615 (5.7%)	35
Skin and subcutaneous tissue disorders
PRURITUS	87/615 (14.1%)	89
RASH	49/615 (8%)	53

Limitations/Caveats

[Not Specified]

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

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