A Study to Evaluate Chronic Hepatitis C Infection

• Sponsor: AbbVie (prior sponsor, Abbott) (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01716585
• Collaborator: (none)
• Enrollment: 636
• Arms: 2
• Duration (Months): 23

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of ABT-450, ritonavir and ABT-267 (ABT-450/r/ABT-267; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) co-administered with ribavirin (RBV) in hepatitis C virus genotype 1 infected treatment-naïve adults.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Infection	Drug: ABT-450/r/ABT-267, ABT-333; Drug: Ribavirin; Drug: Placebo for ABT-450/r/ABT-267; Drug: Placebo for ABT-333; Drug: Placebo for ribavirin	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 636 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 Co-administered With Ribavirin (RBV) in Treatment-Naïve Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection (SAPPHIRE-I)
• Study Start Date: Nov 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ABT-450/r/ABT-267 and ABT-333, plus RBV Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	Drug: ABT-450/r/ABT-267, ABT-333; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet; Other Names: ABT-267 also known as ombitasvir ABT-450 also known as paritaprevir ABT-333 also known as dasabuvir Viekira PAK ; Drug: Ribavirin; Capsule (double-blind treatment period), tablet (open-label treatment period)
Experimental: Placebo Followed by ABT-450/r/ABT-267 and ABT-333, plus RBV Double-blind placebo for 12 weeks, followed by open-label ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	Drug: ABT-450/r/ABT-267, ABT-333; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet; Other Names: ABT-267 also known as ombitasvir ABT-450 also known as paritaprevir ABT-333 also known as dasabuvir Viekira PAK ; Drug: Ribavirin; Capsule (double-blind treatment period), tablet (open-label treatment period); Drug: Placebo for ABT-450/r/ABT-267; Tablet; Drug: Placebo for ABT-333; Tablet; Drug: Placebo for ribavirin; Capsule

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment [12 weeks after the last actual dose of active study drug]

   The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.

Secondary Outcome Measures

1. Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) at Final Treatment Visit During the Double-Blind Treatment Period [At 12 weeks]

   Normalization is defined as alanine aminotransferase less than or equal to the upper limit of normal (ULN) at final treatment visit for participants with alanine aminotransferase greater than ULN at baseline.

2. Percentage of HCV Genotype 1a-infected Participants With Sustained Virologic Response 12 Weeks After Treatment [12 weeks after the last actual dose of active study drug]

   The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.

3. Percentage of HCV Genotype 1b-infected Participants With Sustained Virologic Response 12 Weeks After Treatment [12 weeks after the last actual dose of active study drug]

   The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.

4. Percentage of Participants With On-treatment Virologic Failure During the Double-blind Treatment Period: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm [12 weeks after the last actual dose of active study drug]

   Virologic failure was defined as rebound (hepatitis C virus ribonucleic acid [HCV RNA] ≥ lower limit of quantification [LLOQ] after HCV RNA < LLOQ or increase in HCV RNA of at least 1 log10 IU/mL) or failure to suppress (all on-treatment values of plasma HCV RNA ≥ LLOQ with at least 36 days of treatment) during treatment.

5. Percentage of Participants With Virologic Relapse After Treatment: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm [Within 12 weeks post-treatment]

   Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma hepatitis C virus ribonucleic acid (HCV RNA) greater than or equal to the lower limit of quantification (≥ LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Females must be post-menopausal for at least 2 years or surgically sterile or practicing specific forms of birth control

• Chronic hepatitis C, genotype 1-infection and HCV RNA level greater than 10,000 IU/mL at screening

• Subject has never received antiviral treatment for hepatitis C infection

• No evidence of liver cirrhosis

Exclusion Criteria:

• Positive screen for drugs or alcohol

• Significant sensitivity to any drug

• Use of contraindicated medications within 2 weeks of dosing

• Certain predefined abnormal laboratory tests

• Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie (prior sponsor, Abbott)

Investigators

• Study Director: Nancy Shulman, MD, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01716585
• Other Study ID Numbers: M11-646; 2012-002019-25
• First Posted: Oct 30, 2012
• Last Update Posted: Jul 12, 2021
• Last Verified: Jul 1, 2021

• Keywords provided by AbbVie (prior sponsor, Abbott): Hepatitis C Virus; Hepatitis C Genotype 1; Hepatitis C; Treatment-Naïve; Interferon-Free; Chronic Hepatitis C; Viekira Pak; ombitasvir; paritaprevir; dasabuvir
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ribavirin

Study Results

Participant Flow

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	Placebo Followed by ABT-450/r/ABT-267 and ABT-333, Plus RBV
Arm/Group Description	Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	Double-blind placebo for 12 weeks followed by open-label ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
Period Title: Double-blind Treatment
STARTED	477	159
Randomized But Not Treated	4	1
COMPLETED	464	157
NOT COMPLETED	13	2
Period Title: Double-blind Treatment
STARTED	0	157
COMPLETED	0	150
NOT COMPLETED	0	7

Baseline Characteristics

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	Placebo	Total
Arm/Group Description	Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	Double-blind placebo for 12 weeks	Total of all reporting groups
Overall Participants	473	158	631
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.4 (10.98)	51.2 (10.23)	49.9 (10.82)
Sex: Female, Male (Count of Participants)
Female	202 42.7%	85 53.8%	287 45.5%
Male	271 57.3%	73 46.2%	344 54.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment
Description	The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.
Time Frame	12 weeks after the last actual dose of active study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All randomized participants who received at least 1 dose of blinded study drug.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV
Arm/Group Description	Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
Measure Participants	473
Number [percentage of participants]	96.4 20.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus RBV
	Comments	With a sample size of 450 subjects and assuming that 92% of the subjects in Arm A will achieve SVR12, this study has greater than 90% power to demonstrate non-inferiority with a 2-sided 95% lower confidence bound greater than 70% and greater than 90% power to demonstrate superiority with a 2-sided 95% lower confidence bound greater than 80% (based on the normal approximation of a single binomial proportion). 95% CI calculated using the normal approximation to the binomial distribution.
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Based on historical SVR rates for noncirrhotic HCV treatment-naive subjects administered telaprevir plus peginterferon (pegIFN)/RBV, the lower confidence bound (LCB) of the 95% confidence interval (CI) must have exceeded 70% to achieve noninferiority of the ABT-450/r/ABT-267 and ABT-333, plus RBV treatment group as compared with the historical rate for telaprevir plus pegIFN and RBV, and the LCB of the 95% CI must have exceeded 80% to achieve superiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants with SVR12
	Estimated Value	96.4
	Confidence Interval	(2-Sided) 95%; 94.7 to 98.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	In order to control the Type I error rate at 0.05, a fixed-sequence testing procedure was used to proceed through the primary and first 3 secondary efficacy endpoints in the order numbered below.

2. Secondary Outcome

Title	Percentage of Participants With Normalization of Alanine Aminotransferase (ALT) at Final Treatment Visit During the Double-Blind Treatment Period
Description	Normalization is defined as alanine aminotransferase less than or equal to the upper limit of normal (ULN) at final treatment visit for participants with alanine aminotransferase greater than ULN at baseline.
Time Frame	At 12 weeks

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All randomized participants who received at least 1 dose of blinded study drug and had ALT ≥ ULN of the reference range at baseline were included in the analysis.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV	Placebo
Arm/Group Description	Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks	Double-blind placebo for 12 weeks
Measure Participants	363	114
Number [percentage of participants]	97.0 20.5%	15.8 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus RBV, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	In order to control the Type I error rate at 0.05, a fixed-sequence testing procedure will be used to proceed through the primary and first 3 secondary efficacy endpoints in the order numbered below.
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Percentage of HCV Genotype 1a-infected Participants With Sustained Virologic Response 12 Weeks After Treatment
Description	The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.
Time Frame	12 weeks after the last actual dose of active study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All randomized participants in the Double-blind ABT-450/r/ABT-267 and ABT-333, plus RBV treatment arm with HCV genotype 1a who received at least 1 dose of blinded study drug.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV
Arm/Group Description	Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
Measure Participants	322
Number [percentage of participants]	95.7 20.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus RBV
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Based on historical SVR rates for noncirrhotic HCV treatment-naive subjects of the appropriate HCV genotype 1 subtype administered telaprevir plus pegIFN/RBV, the lower confidence bound (LCB) of the 95% confidence interval (CI) must have exceeded 75% to achieve superiority of the ABT-450/r/ABT-267 and ABT-333, plus RBV treatment group as compared with the historical rate for telaprevir plus pegIFN and RBV.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants with SVR12
	Estimated Value	95.7
	Confidence Interval	(2-Sided) 95%; 93.4 to 97.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI calculated using the normal approximation to the binomial distribution.

4. Secondary Outcome

Title	Percentage of HCV Genotype 1b-infected Participants With Sustained Virologic Response 12 Weeks After Treatment
Description	The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 weeks after the last dose of study drug.
Time Frame	12 weeks after the last actual dose of active study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All randomized participants in the Double-blind ABT-450/r/ABT-267 and ABT-333, plus RBV treatment arm with HCV genotype 1b who received at least 1 dose of blinded study drug.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV
Arm/Group Description	Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
Measure Participants	151
Number [percentage of participants]	98.0 20.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ABT-450/r/ABT-267 and ABT-333, Plus RBV
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence (legacy)
	Comments	Based on historical SVR rates for noncirrhotic HCV treatment-naive subjects of the appropriate HCV genotype 1 subtype administered telaprevir plus pegIFN/RBV, the lower confidence bound (LCB) of the 95% confidence interval (CI) must have exceeded 84% to achieve superiority of the ABT-450/r/ABT-267 and ABT-333, plus RBV treatment group as compared with the historical rate for telaprevir plus pegIFN and RBV.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of Participants with SVR12
	Estimated Value	98.0
	Confidence Interval	(2-Sided) 95%; 95.8 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI calculated using the normal approximation to the binomial distribution.

5. Secondary Outcome

Title	Percentage of Participants With On-treatment Virologic Failure During the Double-blind Treatment Period: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm
Description	Virologic failure was defined as rebound (hepatitis C virus ribonucleic acid [HCV RNA] ≥ lower limit of quantification [LLOQ] after HCV RNA < LLOQ or increase in HCV RNA of at least 1 log10 IU/mL) or failure to suppress (all on-treatment values of plasma HCV RNA ≥ LLOQ with at least 36 days of treatment) during treatment.
Time Frame	12 weeks after the last actual dose of active study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All randomized participants who received at least 1 dose of blinded study drug in the Double-blind ABT-450/r/ABT-267 and ABT-333, plus RBV treatment arm.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV
Arm/Group Description	Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
Measure Participants	473
Number (95% Confidence Interval) [percentage of participants]	0.2 0%

6. Secondary Outcome

Title	Percentage of Participants With Virologic Relapse After Treatment: ABT-450/r/ABT-267 and ABT-333, Plus RBV Arm
Description	Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma hepatitis C virus ribonucleic acid (HCV RNA) greater than or equal to the lower limit of quantification (≥ LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment.
Time Frame	Within 12 weeks post-treatment

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) Population: All randomized participants who received at least 1 dose of blinded study drug with HCV RNA < LLOQ at the final treatment visit who completed treatment in the Double-blind ABT-450/r/ABT-267 and ABT-333, plus RBV treatment arm.

Arm/Group Title	ABT-450/r/ABT-267 and ABT-333, Plus RBV
Arm/Group Description	Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
Measure Participants	463
Number (95% Confidence Interval) [percentage of participants]	1.5 0.3%

Adverse Events

Time Frame	Adverse events (AEs) were collected from the start of active study drug administration (double-blind [DB]/open-label, OL active) to 30 days after the last dose of active study drug 16 weeks.
Adverse Event Reporting Description	DB Placebo Arm: AEs collected from start of placebo until 30 days following discontinuation of placebo and prior to the OL period (if applicable; total 16 weeks). Serious AES collected from informed consent until the end of participation in the study (12 weeks, DB period; 12 weeks, OL period + 48-week post-treatment period; total up to 72 weeks).
Arm/Group Title	Double Blind ABT-450/r/ABT-267 and ABT-333, Plus RBV		Double Blind Placebo		Open Label ABT-450/r/ABT-267 and ABT-333, Plus RBV
Arm/Group Description	Double-blind ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks		Double-blind placebo for 12 weeks		Open-label ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks
All Cause Mortality
	Double Blind ABT-450/r/ABT-267 and ABT-333, Plus RBV		Double Blind Placebo		Open Label ABT-450/r/ABT-267 and ABT-333, Plus RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Double Blind ABT-450/r/ABT-267 and ABT-333, Plus RBV		Double Blind Placebo		Open Label ABT-450/r/ABT-267 and ABT-333, Plus RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/473 (2.1%)		0/158 (0%)		2/157 (1.3%)
Blood and lymphatic system disorders
ANAEMIA	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
Cardiac disorders
SINUS TACHYCARDIA	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
VENTRICULAR EXTRASYSTOLES	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
Gastrointestinal disorders
ABDOMINAL PAIN	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
DIARRHOEA	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
NAUSEA	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
VOMITING	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
General disorders
CHILLS	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
NON-CARDIAC CHEST PAIN	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
Hepatobiliary disorders
BILIARY COLIC	0/473 (0%)		0/158 (0%)		1/157 (0.6%)
CHOLECYSTITIS	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
Infections and infestations
APPENDICITIS	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
LOBAR PNEUMONIA	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
POSTOPERATIVE WOUND INFECTION	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
SUBCUTANEOUS ABSCESS	0/473 (0%)		0/158 (0%)		1/157 (0.6%)
Injury, poisoning and procedural complications
LUMBAR VERTEBRAL FRACTURE	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
OVERDOSE	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
NON-SMALL CELL LUNG CANCER	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
Nervous system disorders
ENCEPHALOPATHY	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
HYPOXIA	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
MEDIASTINAL MASS	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
Vascular disorders
AORTIC STENOSIS	1/473 (0.2%)		0/158 (0%)		0/157 (0%)
Other (Not Including Serious) Adverse Events
	Double Blind ABT-450/r/ABT-267 and ABT-333, Plus RBV		Double Blind Placebo		Open Label ABT-450/r/ABT-267 and ABT-333, Plus RBV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	391/473 (82.7%)		108/158 (68.4%)		117/157 (74.5%)
Blood and lymphatic system disorders
ANAEMIA	24/473 (5.1%)		0/158 (0%)		14/157 (8.9%)
Gastrointestinal disorders
ABDOMINAL PAIN UPPER	29/473 (6.1%)		5/158 (3.2%)		8/157 (5.1%)
DIARRHOEA	65/473 (13.7%)		11/158 (7%)		19/157 (12.1%)
DRY MOUTH	19/473 (4%)		9/158 (5.7%)		0/157 (0%)
DYSPEPSIA	26/473 (5.5%)		7/158 (4.4%)		6/157 (3.8%)
NAUSEA	112/473 (23.7%)		22/158 (13.9%)		24/157 (15.3%)
VOMITING	23/473 (4.9%)		6/158 (3.8%)		9/157 (5.7%)
General disorders
ASTHENIA	59/473 (12.5%)		6/158 (3.8%)		10/157 (6.4%)
FATIGUE	164/473 (34.7%)		45/158 (28.5%)		35/157 (22.3%)
IRRITABILITY	26/473 (5.5%)		4/158 (2.5%)		6/157 (3.8%)
Infections and infestations
NASOPHARYNGITIS	33/473 (7%)		10/158 (6.3%)		11/157 (7%)
UPPER RESPIRATORY TRACT INFECTION	22/473 (4.7%)		8/158 (5.1%)		10/157 (6.4%)
Metabolism and nutrition disorders
DECREASED APPETITE	37/473 (7.8%)		5/158 (3.2%)		11/157 (7%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	23/473 (4.9%)		9/158 (5.7%)		9/157 (5.7%)
BACK PAIN	22/473 (4.7%)		7/158 (4.4%)		9/157 (5.7%)
MYALGIA	21/473 (4.4%)		8/158 (5.1%)		6/157 (3.8%)
Nervous system disorders
DIZZINESS	38/473 (8%)		6/158 (3.8%)		5/157 (3.2%)
HEADACHE	156/473 (33%)		42/158 (26.6%)		26/157 (16.6%)
Psychiatric disorders
ANXIETY	22/473 (4.7%)		5/158 (3.2%)		8/157 (5.1%)
INSOMNIA	67/473 (14.2%)		12/158 (7.6%)		21/157 (13.4%)
SLEEP DISORDER	24/473 (5.1%)		4/158 (2.5%)		4/157 (2.5%)
Respiratory, thoracic and mediastinal disorders
COUGH	34/473 (7.2%)		8/158 (5.1%)		7/157 (4.5%)
DYSPNOEA	38/473 (8%)		4/158 (2.5%)		12/157 (7.6%)
DYSPNOEA EXERTIONAL	24/473 (5.1%)		3/158 (1.9%)		8/157 (5.1%)
Skin and subcutaneous tissue disorders
DRY SKIN	27/473 (5.7%)		2/158 (1.3%)		7/157 (4.5%)
PRURITUS	80/473 (16.9%)		7/158 (4.4%)		16/157 (10.2%)
RASH	51/473 (10.8%)		9/158 (5.7%)		8/157 (5.1%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.