Trial Outcomes & Findings for A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection (NCT NCT00851890)

Last Updated: 2018-07-02

Results Overview

Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. The maximal change during monotherapy was nadir minus the baseline log10 HCV RNA level. Nadir was defined as the lowest log10 HCV RNA level any time after the first dose of study drug on Day 1 through the last log10 HCV RNA level before the first dose of study drug on Day 3. Data are reported as the least squares mean change from nadir ± standard error.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Prior to the first dose on Day 1 to before first dose on Day 3

Results posted on

2018-07-02

Participant Flow

Participant milestones

Participant milestones
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Overall Study STARTED	8	8	8	6
Overall Study COMPLETED	8	7	8	5
Overall Study NOT COMPLETED	0	1	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Overall Study Lost to Follow-up	0	1	0	1

Baseline Characteristics

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-333 Alone and in Combination With Pegylated Interferon (pegIFN) and Ribavirin (RBV) in Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Total n=30 Participants Total of all reporting groups
Age, Continuous	45.8 years STANDARD_DEVIATION 9.62 • n=5 Participants	44.6 years STANDARD_DEVIATION 12.96 • n=7 Participants	47.8 years STANDARD_DEVIATION 9.50 • n=5 Participants	48.2 years STANDARD_DEVIATION 7.31 • n=4 Participants	46.5 years STANDARD_DEVIATION 9.80 • n=21 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	1 Participants n=4 Participants	9 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	5 Participants n=4 Participants	21 Participants n=21 Participants

PRIMARY outcome

Timeframe: Prior to the first dose on Day 1 to before first dose on Day 3

Population: Participants received at least 1 dose of study drug and had at least 1 post-baseline measurement of HCV RNA.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Monotherapy Treatment	-1.01 log10 IU/mL Standard Error 0.18	-0.78 log10 IU/mL Standard Error 0.18	-0.68 log10 IU/mL Standard Error 0.18	-0.26 log10 IU/mL Standard Error 0.21

PRIMARY outcome

Timeframe: Prior to the first dose on Day 1 through Day 28

Population: Participants received at least 1 dose of study drug and had at least 1 post-baseline measurement of HCV RNA.

Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. The maximal change during treatment was nadir minus the baseline log10 HCV RNA level. Nadir was defined as the lowest log10 HCV RNA level any time after the first dose of study drug on Day 1 through the last log10 HCV RNA level on Day 28. Data are reported as the least squares mean change from nadir ± standard error.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Mean Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28	-3.65 log10 IU/mL Standard Error 0.51	-3.96 log10 IU/mL Standard Error 0.51	-3.59 log10 IU/mL Standard Error 0.51	-1.37 log10 IU/mL Standard Error 0.59

PRIMARY outcome

Timeframe: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2

Population: Participants received at least 1 dose of study drug and had sufficient concentrations to characterize the pharmacokinetic parameters.

Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Maximum Plasma Concentration (Cmax) of ABT-333	883 ng/mL Standard Deviation 575	1236 ng/mL Standard Deviation 724	1975 ng/mL Standard Deviation 619	—

PRIMARY outcome

Timeframe: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2

Population: Participants received at least 1 dose of study drug and had sufficient concentrations to characterize the pharmacokinetic parameters.

Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Time to Maximum Plasma Concentration (Tmax) of ABT-333	3.80 Hours Standard Deviation 0.71	3.50 Hours Standard Deviation 0.93	3.50 Hours Standard Deviation 0.93	—

PRIMARY outcome

Timeframe: Pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours post-dose on Day 1; and pre-dose on Day 2

Population: Participants received at least 1 dose of study drug and had sufficient concentrations to characterize the pharmacokinetic parameters.

Blood samples were collected pre-dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and pre-dose on Day 2. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) measures the total exposure of a drug in blood plasma. The AUC12 of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC12) of ABT-333	5852 ng*hr/mL Standard Deviation 4159	7548 ng*hr/mL Standard Deviation 4016	12411 ng*hr/mL Standard Deviation 4122	—

PRIMARY outcome

Timeframe: Prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28

Population: Participants received at least 1 dose of study drug and had sufficient concentrations to characterize the pharmacokinetic parameters. When a different number of participants at a specific timepoint was used to analyze the data in the outcome measure, the n (number of participants) for each arm is denoted in the Category Title.

Blood samples were collected prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28. The samples were analyzed for the concentration of pegIFN (measured in ng/mL) using validated analytical methods and estimated using non-compartmental methods. Data are reported as the mean ± standard deviation.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Serum Concentrations of Pegylated Interferon (pegIFN) 4 hours after morning dose on Day 3 (n=7, 8, 8, 6)	0.70 ng/mL Standard Deviation 0.67	1.36 ng/mL Standard Deviation 1.51	0.09 ng/mL Standard Deviation 0.25	0.58 ng/mL Standard Deviation 0.70
Serum Concentrations of Pegylated Interferon (pegIFN) Prior to morning dose on Day 3	0.00 ng/mL Standard Deviation 0.00	0.00 ng/mL Standard Deviation 0.00	0.00 ng/mL Standard Deviation 0.00	0.00 ng/mL Standard Deviation 0.00
Serum Concentrations of Pegylated Interferon (pegIFN) Day 4 (n=8, 8, 7, 6)	6.96 ng/mL Standard Deviation 4.04	6.51 ng/mL Standard Deviation 5.15	4.95 ng/mL Standard Deviation 4.50	3.42 ng/mL Standard Deviation 2.11
Serum Concentrations of Pegylated Interferon (pegIFN) Day 5	9.06 ng/mL Standard Deviation 5.15	7.91 ng/mL Standard Deviation 4.82	5.57 ng/mL Standard Deviation 4.29	4.85 ng/mL Standard Deviation 3.17
Serum Concentrations of Pegylated Interferon (pegIFN) Day 10	7.91 ng/mL Standard Deviation 2.21	6.47 ng/mL Standard Deviation 3.18	4.72 ng/mL Standard Deviation 3.28	4.48 ng/mL Standard Deviation 2.77
Serum Concentrations of Pegylated Interferon (pegIFN) Day 17 (n=8, 8, 8, 5)	12.3 ng/mL Standard Deviation 3.99	9.26 ng/mL Standard Deviation 4.28	8.73 ng/mL Standard Deviation 5.92	7.05 ng/mL Standard Deviation 5.06
Serum Concentrations of Pegylated Interferon (pegIFN) Day 24 (n=8, 7, 8, 5)	12.8 ng/mL Standard Deviation 3.45	12.1 ng/mL Standard Deviation 4.78	12.1 ng/mL Standard Deviation 7.11	8.58 ng/mL Standard Deviation 6.45
Serum Concentrations of Pegylated Interferon (pegIFN) Day 28 (n=8, 7, 8, 5)	17.4 ng/mL Standard Deviation 4.67	17.3 ng/mL Standard Deviation 3.95	17.0 ng/mL Standard Deviation 10.1	14.3 ng/mL Standard Deviation 10.0

PRIMARY outcome

Timeframe: Prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28

Blood samples were collected prior to the morning dose on Day 3; 4 hours after the morning dose on Day 3; prior to the morning dose on Days 4 and 5; and single samples were collected on Days 10, 17, 24, and 28. The samples were analyzed for the concentration of RBV (measured in ng/mL) using validated analytical methods and estimated using non-compartmental methods. Data are reported as the mean ± standard deviation.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Plasma Concentrations of Ribavirin (RBV) Day 24 (n=8, 7, 8, 5)	1.76 ng/mL Standard Deviation 0.31	1.91 ng/mL Standard Deviation 0.38	1.60 ng/mL Standard Deviation 0.39	1.49 ng/mL Standard Deviation 0.19
Plasma Concentrations of Ribavirin (RBV) Prior to morning dose on Day 3	0.00 ng/mL Standard Deviation 0.00	0.00 ng/mL Standard Deviation 0.00	0.00 ng/mL Standard Deviation 0.00	0.00 ng/mL Standard Deviation 0.00
Plasma Concentrations of Ribavirin (RBV) 4 hours after morning dose on Day 3	0.46 ng/mL Standard Deviation 0.16	0.61 ng/mL Standard Deviation 0.40	0.51 ng/mL Standard Deviation 0.15	0.54 ng/mL Standard Deviation 0.19
Plasma Concentrations of Ribavirin (RBV) Day 4 (n=5, 7, 5, 5)	0.33 ng/mL Standard Deviation 0.07	0.46 ng/mL Standard Deviation 0.11	0.29 ng/mL Standard Deviation 0.17	0.36 ng/mL Standard Deviation 0.05
Plasma Concentrations of Ribavirin (RBV) Day 5 (n=6, 6, 8, 5)	0.61 ng/mL Standard Deviation 0.10	0.69 ng/mL Standard Deviation 0.22	0.48 ng/mL Standard Deviation 0.20	0.55 ng/mL Standard Deviation 0.14
Plasma Concentrations of Ribavirin (RBV) Day 10 (n=7, 8, 8, 6)	1.05 ng/mL Standard Deviation 0.17	1.24 ng/mL Standard Deviation 0.29	1.02 ng/mL Standard Deviation 0.38	1.05 ng/mL Standard Deviation 0.21
Plasma Concentrations of Ribavirin (RBV) Day 17 (n=8, 8, 8, 5)	1.47 ng/mL Standard Deviation 0.29	1.67 ng/mL Standard Deviation 0.40	1.32 ng/mL Standard Deviation 0.36	1.34 ng/mL Standard Deviation 0.52
Plasma Concentrations of Ribavirin (RBV) Day 28 (n=8, 7, 8, 5)	1.76 ng/mL Standard Deviation 0.44	2.07 ng/mL Standard Deviation 0.53	1.56 ng/mL Standard Deviation 0.46	1.68 ng/mL Standard Deviation 0.66

PRIMARY outcome

Timeframe: AEs were collected from the time of study drug administration to 30 days after last dose of study drug (8 Weeks)

Population: Participants received at least 1 dose of study drug.

An AE was any untoward medical occurrence that did not have a causal relationship with treatment. An Adverse Drug Reaction (ADR) was any noxious and undesired reaction related to the experimental drug or experiment. A serious adverse event (SAE) was an AE that resulted in death, was life-threatening, resulted in or prolonged hospitalization, resulted in congenital anomaly, was persistent or caused significant disability/incapacity, spontaneous or elective abortion, or required intervention to prevent a serious outcome. AEs were rated for severity as either: 1. Mild - transient and easily tolerated; 2. Moderate - caused discomfort and interrupted usual activities; 3. Severe - caused considerable interference with usual activities, may be incapacitating or life-threatening. AEs related to direct-acting antiviral agents (DAAs) were assessed as being either probably or possibly related by the investigator.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Number of Participants Having Treatment-emergent Adverse Events (AEs) Any AE	8 participants	8 participants	8 participants	5 participants
Number of Participants Having Treatment-emergent Adverse Events (AEs) Any AE at least possibly drug related	4 participants	3 participants	2 participants	1 participants
Number of Participants Having Treatment-emergent Adverse Events (AEs) Any severe AE	1 participants	0 participants	0 participants	0 participants
Number of Participants Having Treatment-emergent Adverse Events (AEs) Any serious AE	0 participants	0 participants	0 participants	0 participants
Number of Participants Having Treatment-emergent Adverse Events (AEs) Any AE leading to discontinuation of study drug	0 participants	0 participants	0 participants	0 participants
Number of Participants Having Treatment-emergent Adverse Events (AEs) Any fatal events	0 participants	0 participants	0 participants	0 participants
Number of Participants Having Treatment-emergent Adverse Events (AEs) Deaths	0 participants	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 28 and Final Visit

Population: Participants received at least 1 dose of study drug and had at least 1 post-baseline measurement of HCV RNA. When a different number of participants at a specific timepoint was used to analyze the data in the outcome measure, the n (number of participants) for each arm is denoted in the Category Title.

Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (reported as log10 IU/mL) were determined using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1 and the Day 28 or Final Visit value was the last HCV RNA measurement during the study. Data are reported as the least squares mean change from baseline ± standard error.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28 or Final Visit Day 28 (n=8, 7, 7, 5)	-3.65 log10 IU/mL Standard Error 0.53	-3.67 log10 IU/mL Standard Error 0.57	-3.24 log10 IU/mL Standard Error 0.57	-1.45 log10 IU/mL Standard Error 0.68
Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels Through Day 28 or Final Visit Final Visit	-3.65 log10 IU/mL Standard Error 0.53	-3.86 log10 IU/mL Standard Error 0.53	-3.48 log10 IU/mL Standard Error 0.53	-1.35 log10 IU/mL Standard Error 0.61

SECONDARY outcome

Timeframe: Prior to the first dose on Day 1 and Day 28

Population: Participants received at least 1 dose of study drug and had at least 1 post-baseline measurement of HCV RNA.

Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The baseline value was the HCV RNA measurement before the first dose of ABT-333 on Day 1. Data are reported as the percentage of participants.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Percentage of Participants With at Least a 2 log10 Maximal Decrease in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-333 Treatment	87.5 percentage of participants	87.5 percentage of participants	62.5 percentage of participants	16.7 percentage of participants

SECONDARY outcome

Timeframe: Day 28 or Final Visit

Population: Participants received at least 1 dose of study drug and had at least 1 post-baseline measurement of hepatitis C virus ribonucleic acid (HCV RNA).

Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The lower limit of quantification (LLOQ) was defined as HCV RNA levels ≤ 25 IU/mL. Data are reported as the percentage of participants.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 25 IU/mL (the Lower Limit of Quantitation [LLOQ]) at Day 28 or Final Visit	37.5 percentage of participants	25.0 percentage of participants	62.5 percentage of participants	0.00 percentage of participants

SECONDARY outcome

Timeframe: Day 28 or Final Visit

Population: Participants received at least 1 dose of study drug and had at least 1 post-baseline measurement of hepatitis C virus ribonucleic acid (HCV RNA).

Serum hepatitis C virus ribonucleic acid (HCV RNA) levels (measured in IU/mL) were determined for each sample using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay. The lower limit of detection (LLOD) was defined as a HCV RNA level equal to 10 IU/mL. Data are reported as the percentage of participants.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV n=6 Participants Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Percentage of Participants With Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels ≤ 10 IU/mL (Lower Limit of Detection [LLOD]) at Day 28 or Final Visit	37.5 percentage of participants	0.00 percentage of participants	12.5 percentage of participants	0.00 percentage of participants

SECONDARY outcome

Timeframe: Days 1, 5, 10, 17, 24 and 28

Samples from Days 1, 5, 10, 17, 24 and 28 were analyzed for the presence of resistance-associated amino acids using population sequencing and compared to the baseline non-structural viral protein 5B (NS5B) sequence to assess amino acid changes. The amino acid sequence of NS5B before the first dose of ABT-333 on Day 1 was defined as the baseline sequence. The number of participants with variants at resistance-associated amino acid positions in the post-baseline samples are presented.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28 Day 1	0 participants	1 participants	0 participants	—
Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28 Day 5 (n=6, 8, 7)	1 participants	1 participants	1 participants	—
Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28 Day 10 (n=6, 6, 7)	1 participants	1 participants	2 participants	—
Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28 Day 17 (n=5, 5, 6)	2 participants	2 participants	2 participants	—
Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28 Day 24 (n=3, 3, 2)	3 participants	3 participants	1 participants	—
Number of Participants With Resistance-Associated Variants in Non-structural Viral Protein 5B (NS5B) Through Day 28 Day 28 (n=4, 3, 3)	2 participants	2 participants	3 participants	—

SECONDARY outcome

Timeframe: Days 1 through 28

Population: Participants received at least 1 dose of study drug and had at least 1 post-baseline measurement of HCV RNA.

Phenotypic resistance to ABT-333 was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the corresponding baseline sample, and the maximal fold change in EC50 from baseline over the Day 5-28 period. The resistance sample drawn before the first dose of ABT-333 on Day 1 was defined as the baseline sample. The number of participants with phenotypic resistance in the post-baseline samples are presented.

Outcome measures

Outcome measures
Measure	ABT-333 (300 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 300 mg ABT-333 BID for 2 days followed by 300 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (600 mg) Twice Daily (BID) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 600 mg ABT-333 BID for 2 days followed by 600 mg ABT-333 BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	ABT-333 (1200 mg) Once Daily (QD) + pegIFN/RBV n=8 Participants Hepatitis C virus (HCV) positive, treatment-naive participants received 1200 mg ABT-333 QD for 2 days followed by 1200 mg ABT-333 QD with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.	Placebo + pegIFN/RBV Hepatitis C virus (HCV) positive, treatment-naïve participants received matching placebo once daily (QD) or twice daily (BID) for 2 days followed by placebo QD or BID with pegylated interferon/ribavirin (pegIFN/RBV) for 26 days. Pegylated interferon was administered at 180 μg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day.
Number of Participants With Maximal Phenotypic Resistance to ABT-333 >10 Fold Relative to Baseline Through Day 28	4 participants	4 participants	5 participants	—

Adverse Events

ABT-333 (300 mg) Twice Daily (BID) + (pegIFN/RBV)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

ABT-333 (600 mg) Twice Daily (BID) + (pegIFN/RBV)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

ABT-333 (1200 mg) Once Daily (QD) + (pegIFN/RBV)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Placebo + (pegIFN/RBV)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Global Medical Services

AbbVie (prior sponsor, Abbott)

Phone: 800-633-9110

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER