Hepatitis C, HCV, Chronic Hepatitis C Infection, Hepatitis C Genotype 1
Conditions
Brief summary
This study assessed the safety, tolerability, pharmacokinetics, and antiviral activity of multiple oral doses of ABT-450/ritonavir (r), ABT-333 (also known as dasabuvir), or ABT-072 in hepatitis C virus (HCV), genotype 1-infected, treatment-naïve adults.
Detailed description
This was a Phase 2a, randomized, blinded, placebo-controlled, dose-ranging study in chronically, hepatitis C virus (HCV) genotype 1-infected participants designed to explore the safety, tolerability, pharmacokinetics, antiviral activity, as well as the evolution and persistence to resistance of ABT-450/r, ABT-333, or ABT-072. Participants were treated with ABT-450/r, ABT-333, or ABT-072 monotherapy for 3 days, followed by 81 days (12 weeks minus 3 days of monotherapy) of ABT-450/r, ABT-333, or ABT-072 combined with pegylated interferon/ribavirin (pegIFN/RBV), followed by 36 weeks of pegIFN/RBV alone. Participants randomized to an ABT-450/r treatment group who achieved rapid virologic response (RVR) and had HCV ribonucleic acid (RNA) levels \< 25 IU/mL at all subsequent visits were eligible to stop pegIFN/RBV therapy on or after Week 24.
Interventions
DRUGABT-450
50 mg capsules co-administered with ritonavir
DRUGABT-072
50 mg tablet
DRUGABT-333
400 mg tablet
DRUGRitonavir
100 mg capsules co-administered with ABT-450
Syringe, 180 µg/0.5 mL for subcutaneous injections
DRUGRibavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
OTHERPlacebo
Matching placebo for ABT-450/r, ABT-072, or ABT-333 monotherapy at each dose level
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis C virus (HCV), genotype 1 infection (HCV ribonucleic acid level greater than or equal to 100,000 IU/mL) at screening * Liver biopsy within 3 years with histology consistent with HCV-induced liver damage, with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV * Treatment naïve male or female between the ages of 18 and 65 * Females must be post-menopausal for more than 2 years or surgically sterile * Negative screen for drugs and alcohol * Negative hepatitis B surface antigen (HBsAg) and anti-human immunodeficiency virus antibodies (anti-HIV Ab) * No use of cytochrome P450 3A (CYP3A) and cytochrome P450 2C8 (CYP2C8) enzyme inducers or inhibitors within 1 month of dosing * Be in a condition of general good health, as perceived by the investigator, other than HCV infection
Exclusion criteria
* Significant sensitivity to any drug * Use of herbal supplements within 2 weeks prior to study drug dosing * History of major depression within 2 years * Prior treatment with any investigational or commercially available anti-HCV agents * Abnormal laboratory tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC12) Post-dose of ABT-333 | Immediately prior to morning dose (time 0 hours) and at 2, 4, 8, and 12 hours after the morning dose on Day 1 | Blood samples were collected immediately prior to morning dose (time 0 hours) and at 2, 4, 8, and 12 hours after the morning dose on Day 1. 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) is a method of measurement to determine 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. |
| Maximum Plasma Concentration (Cmax) of ABT-450 | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-450 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-450 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. |
| Time to Maximum Plasma Concentration (Tmax) of ABT-450 | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-450 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-450 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. |
| Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-450 | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-450 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ABT-450 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. |
| Maximum Plasma Concentration (Cmax) of Ritonavir | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ritonavir 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 ritonavir was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. |
| Time to Maximum Plasma Concentration (Tmax) of Ritonavir | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ritonavir 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 ritonavir was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. |
| Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of Ritonavir | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ritonavir using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ritonavir was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. |
| Maximum Plasma Concentration (Cmax) of ABT-072 | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-072 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-072 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. |
| Time to Maximum Plasma Concentration (Tmax) of ABT-072 | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-072 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-072 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. |
| Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-072 | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-072 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ABT-072 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation. |
| Maximum Plasma Concentration (Cmax) of ABT-333 | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). 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. |
| Time to Maximum Plasma Concentration (Tmax) of ABT-333 | Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose) | Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). 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. |
| Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | Prior to dosing on Day 1 to before the morning dose on Day 4 | Plasma 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 that had a lower limit of detection of 10 IU/mL and a lower limit of quantification of 25 IU/mL. The baseline value was the HCV RNA level before the first dose of study drug on Day 1. The maximal change during monotherapy was the difference from baseline to the lowest log10 HCV RNA level anytime 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 4. Data are reported as the mean ± standard deviation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | Baseline and Week 12 | Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay that had a lower limit of detection of 10 IU/mL and a lower limit of quantification of 25 IU/mL. Partial early virologic response (EVR) was defined as HCV RNA levels that decreased \> 2 log10 IU/mL at Week 12 as compared to baseline. The baseline value was the last measurement before the first dose on Day 1. Data are reported as the percentage of participants with partial EVR. |
| Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | Week 12 | Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay that had a lower limit of detection of 10 IU/mL and a lower limit of quantification (LLOQ) of 25 IU/mL. Complete EVR was defined as HCV RNA levels \< LLOQ (\< 25 IU/mL) at Week 12. Data are reported as the percentage of participants with cEVR. |
| Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | Week 4 | Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay that had a lower limit of detection of 10 IU/mL and a lower limit of quantification (LLOQ) of 25 IU/mL. Rapid virologic response was defined as HCV RNA level \< LLOQ (\< 25 IU/mL) at Week 4. Data are reported as the percentage of participants with RVR. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ED-5D Visual Analog Scale (ED-5D VAS) Score | Baseline and Post-treatment Week 24 | The ED-5D VAS was a self-rating survey used to capture the current health status of a participant and ranged from 0 (the worst imaginable health state) to 100 (best imaginable health state). Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation. |
| Change From Baseline in EQ-5D (3 Level) Health Index Score | Baseline and Post-treatment Week 24 | The EQ-5D was a health state questionnaire used to measure five health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). The combination of responses from all five dimensions were derived into an index score ranging from 0 to 1; a higher score indicated a more preferable health utility value from the societal perspectives. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation. |
| Change From Baseline in SF-36 Physical Component Summary (PCS) | Baseline and Post-treatment Week 24 | The Physical Component Summary (PCS) of the SF-36 was used to measure the overall physical health status of a participant. The aggregated score of the SF-36 PCS score was standardized using a linear T-score transformation with a mean of 50 and a standard deviation of 10; a higher score indicated better physical function and well-being. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation. |
| Change From Baseline in SF-36 Mental Component Summary (MCS) | Baseline and Post-treatment Week 24 | The Mental Component Summary (MCS) of the SF-36 was used to measure the overall mental health status of participants. The aggregated score of the SF-36 MPS was standardized using a linear T-score transformation with a mean of 50 and a standard deviation of 10; a higher score indicated better mental function and well-being. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation. |
| Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Baseline and Day 4 | Baseline samples were analyzed for resistance-associated amino acid variants using population and clonal sequencing and were compared with the appropriate reference sequence (1a-H77 or 1b-Con1). Phenotypic resistance to ABT-072 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Available samples at Day 4 with HCV RNA ≥ 1000 IU/mL were analyzed for the presence of resistance-associated variants using population and clonal sequencing and were compared with the baseline sequences to assess amino acid changes. Phenotypic resistance to ABT-072 at Day 4 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance are presented. |
| Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Baseline and Day 4 | Baseline samples were analyzed for resistance-associated amino acid variants using population and clonal sequencing and were compared with the appropriate reference sequence (1a-H77 or 1b-Con1). Phenotypic resistance to ABT-450 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Available samples at Day 4 with HCV RNA ≥ 1000 IU/mL were analyzed for resistance-associated variants using population and clonal sequencing and were compared with the baseline sequences to assess amino acid changes. Phenotypic resistance to ABT-450 at Day 4 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance are presented. |
| Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B) | Baseline and Day 4 | Baseline samples were analyzed for resistance-associated amino acid variants using population and clonal sequencing and were compared with the appropriate reference sequence (1a-H77 or 1b-Con1). Phenotypic resistance to ABT-333 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Available samples at Day 4 with HCV RNA ≥ 1000 IU/mL were analyzed for the presence of resistance-associated variants using population and clonal sequencing and were compared with the baseline sequences to assess amino acid changes. Phenotypic resistance to ABT-333 at Day 4 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance are presented. |
| Change From Baseline in Hepatitis C Virus Patient-reported Outcomes (HCV-PRO) Total Score | Baseline up to Post-treatment Week 24 | The Hepatitis C Virus Patient-report Outcomes (HCV-PRO, formerly known as HCV Quality of Life) survey was used to assess disease-specific function and well-being on a scale from 0 to 100; a higher score indicated relatively good function and well-being of treated participants. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are reported as the group mean change from baseline ± standard deviation. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV Participants received 50 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. | 8 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV Participants received 100 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. | 8 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV Participants received 200 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. | 8 |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV Participants received 100 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. | 8 |
| ABT-072 (300 mg) Once Daily (QD) + pegIFN/RBV Participants received 300 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. | 8 |
| ABT-072 (600 mg) Once Daily (QD) + pegIFN/RBV Participants received 600 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. | 7 |
| ABT-333 (400 mg) Twice a Day (BID) + pegIFN/RBV Participants received 400 mg ABT-333 monotherapy twice a day for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. | 8 |
| ABT-333 (800 mg) Twice Daily (BID) + pegIFN/RBV Participants received 800 mg ABT-333 monotherapy twice a day for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. | 8 |
| Placebo + pegIFN/RBV Participants received matching placebo for ABT-450/r, ABT-072, or ABT-333 monotherapy at each dose level for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. | 11 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | ABT-072 (300 mg) Once Daily (QD) + pegIFN/RBV | ABT-072 (600 mg) Once Daily (QD) + pegIFN/RBV | ABT-333 (400 mg) Twice a Day (BID) + pegIFN/RBV | ABT-333 (800 mg) Twice Daily (BID) + pegIFN/RBV | Placebo + pegIFN/RBV | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 48.4 years STANDARD_DEVIATION 9.36 | 50.9 years STANDARD_DEVIATION 2.59 | 50.6 years STANDARD_DEVIATION 9.26 | 53.5 years STANDARD_DEVIATION 5.4 | 51.3 years STANDARD_DEVIATION 7.76 | 40.9 years STANDARD_DEVIATION 11.25 | 49.6 years STANDARD_DEVIATION 8.37 | 53.5 years STANDARD_DEVIATION 6.46 | 51.5 years STANDARD_DEVIATION 6.36 | 50.2 years STANDARD_DEVIATION 8.01 |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 4 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 16 Participants |
| Sex: Female, Male Male | 7 Participants | 5 Participants | 4 Participants | 5 Participants | 7 Participants | 7 Participants | 6 Participants | 8 Participants | 9 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 8 / 8 | 8 / 8 | 8 / 8 | 8 / 8 | 7 / 7 | 8 / 8 | 8 / 8 | 10 / 11 |
| serious Total, serious adverse events | 1 / 8 | 0 / 8 | 0 / 8 | 1 / 8 | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 8 | 0 / 11 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC12) Post-dose of ABT-333
Blood samples were collected immediately prior to morning dose (time 0 hours) and at 2, 4, 8, and 12 hours after the morning dose on Day 1. 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) is a method of measurement to determine 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.
Time frame: Immediately prior to morning dose (time 0 hours) and at 2, 4, 8, and 12 hours after the morning dose on Day 1
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC12) Post-dose of ABT-333 | 4315 ng*hr/mL | Standard Deviation 2176 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC12) Post-dose of ABT-333 | 6431 ng*hr/mL | Standard Deviation 1914 |
Primary
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-072
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-072 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ABT-072 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-072 | 3678 ng*hr/mL | Standard Deviation 1742 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-072 | 9413 ng*hr/mL | Standard Deviation 3125 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-072 | 14126 ng*hr/mL | Standard Deviation 6102 |
Primary
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-450
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-450 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ABT-450 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-450 | 250 ng*hr/mL | Standard Deviation 245 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-450 | 1122 ng*hr/mL | Standard Deviation 992 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-450 | 17351 ng*hr/mL | Standard Deviation 15841 |
Primary
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of Ritonavir
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ritonavir using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ritonavir was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of Ritonavir | 4518 ng*hr/mL | Standard Deviation 5063 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of Ritonavir | 7638 ng*hr/mL | Standard Deviation 6284 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of Ritonavir | 8663 ng*hr/mL | Standard Deviation 5006 |
Primary
Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment
Plasma 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 that had a lower limit of detection of 10 IU/mL and a lower limit of quantification of 25 IU/mL. The baseline value was the HCV RNA level before the first dose of study drug on Day 1. The maximal change during monotherapy was the difference from baseline to the lowest log10 HCV RNA level anytime 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 4. Data are reported as the mean ± standard deviation.
Time frame: Prior to dosing on Day 1 to before the morning dose on Day 4
Population: Participants received at least one dose of study drug (direct-acting antiviral agent) and have both baseline and at least one post-baseline measurement of HCV RNA levels during monotherapy treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | -4.07 log10 IU/mL | Standard Deviation 0.53 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | -3.91 log10 IU/mL | Standard Deviation 0.42 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | -4.11 log10 IU/mL | Standard Deviation 0.32 |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | -1.14 log10 IU/mL | Standard Deviation 0.99 |
| ABT-072 (300 mg) Once Daily (QD) + pegIFN/RBV | Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | -1.07 log10 IU/mL | Standard Deviation 0.41 |
| ABT-072 (600 mg) Once Daily (QD) + pegIFN/RBV | Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | -1.57 log10 IU/mL | Standard Deviation 0.94 |
| ABT-333 (400 mg) Twice a Day (BID) + pegIFN/RBV | Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | -1.08 log10 IU/mL | Standard Deviation 0.68 |
| ABT-333 (800 mg) Twice Daily (BID) + pegIFN/RBV | Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | -0.95 log10 IU/mL | Standard Deviation 0.68 |
| Placebo + pegIFN/RBV | Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment | -0.36 log10 IU/mL | Standard Deviation 0.13 |
Comparison: Eight participants per ABT-450/r group and 11 participants in the placebo group would provide \> 95% power to detect a 1.0 log10 difference with a common standard deviation of 0.5 log10 IU/mL using a two-sided, two-sample t-test with a significance level of 0.05.p-value: <0.001ANCOVA
Comparison: Eight participants per ABT-450/r group and 11 participants in the placebo group would provide \> 95% power to detect a 1.0 log10 difference with a common standard deviation of 0.5 log10 IU/mL using a two-sided, two-sample t-test with a significance level of 0.05.p-value: <0.001ANCOVA
Comparison: Eight participants per ABT-450/r group and 11 participants in the placebo group would provide \> 95% power to detect a 1.0 log10 difference with a common standard deviation of 0.5 log10 IU/mL using a two-sided, two-sample t-test with a significance level of 0.05.p-value: <0.001ANCOVA
Comparison: Eight participants per ABT-072 and 11 participants in the placebo group would provide 92% power to detect a 1.0 log10 difference with a standard deviation of 0.6 log10 IU/mL and a two-sided, two-sample t-test with a significance level of 0.05.p-value: 0.009ANCOVA
Comparison: Eight participants per ABT-072 and 11 participants in the placebo group would provide 92% power to detect a 1.0 log10 difference with a standard deviation of 0.6 log10 IU/mL and a two-sided, two-sample t-test with a significance level of 0.05.p-value: 0.012ANCOVA
Comparison: Eight participants per ABT-072 and 11 participants in the placebo group would provide 92% power to detect a 1.0 log10 difference with a standard deviation of 0.6 log10 IU/mL and a two-sided, two-sample t-test with a significance level of 0.05.p-value: <0.001ANCOVA
Comparison: Eight subjects per ABT-333 group and 11 subjects in the placebo group would provide 82% power to detect a 1.0 log10 IU/mL difference with a standard deviation of 0.7 log10 IU/mL and a 2-sided 2-sample t-test with a significance level of 0.05.p-value: 0.032ANCOVA
Comparison: Eight participants per ABT-333 group and 11 participants in the placebo group would provide 82% power to detect a 1.0 log10 IU/mL difference with a standard deviation of 0.7 log10 IU/mL and a two-sided, two-sample t-test with a significance level of 0.05.p-value: 0.053ANCOVA
Primary
Maximum Plasma Concentration (Cmax) of ABT-072
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-072 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-072 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of ABT-072 | 390 ng/mL | Standard Deviation 153 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of ABT-072 | 1218 ng/mL | Standard Deviation 382 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of ABT-072 | 1748 ng/mL | Standard Deviation 707 |
Primary
Maximum Plasma Concentration (Cmax) of ABT-333
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). 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.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of ABT-333 | 800 ng/mL | Standard Deviation 382 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of ABT-333 | 1201 ng/mL | Standard Deviation 419 |
Primary
Maximum Plasma Concentration (Cmax) of ABT-450
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-450 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-450 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of ABT-450 | 34.4 ng/mL | Standard Deviation 31.7 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of ABT-450 | 165 ng/mL | Standard Deviation 221 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of ABT-450 | 2923 ng/mL | Standard Deviation 2026 |
Primary
Maximum Plasma Concentration (Cmax) of Ritonavir
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ritonavir 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 ritonavir was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of Ritonavir | 563 ng/mL | Standard Deviation 674 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of Ritonavir | 851 ng/mL | Standard Deviation 638 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Maximum Plasma Concentration (Cmax) of Ritonavir | 1098 ng/mL | Standard Deviation 619 |
Primary
Time to Maximum Plasma Concentration (Tmax) of ABT-072
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-072 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-072 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of ABT-072 | 4.5 Hours | Standard Deviation 1.4 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of ABT-072 | 2.8 Hours | Standard Deviation 1 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of ABT-072 | 3.1 Hours | Standard Deviation 1.1 |
Primary
Time to Maximum Plasma Concentration (Tmax) of ABT-333
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). 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.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of ABT-333 | 4.5 Hours | Standard Deviation 5.2 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of ABT-333 | 7.0 Hours | Standard Deviation 8.4 |
Primary
Time to Maximum Plasma Concentration (Tmax) of ABT-450
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-450 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-450 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of ABT-450 | 2.5 Hours | Standard Deviation 0.9 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of ABT-450 | 4.8 Hours | Standard Deviation 3.5 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of ABT-450 | 3.0 Hours | Standard Deviation 1.1 |
Primary
Time to Maximum Plasma Concentration (Tmax) of Ritonavir
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ritonavir 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 ritonavir was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Time frame: Immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose)
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the pharmacokinetic analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of Ritonavir | 4.8 Hours | Standard Deviation 2.8 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of Ritonavir | 5.3 Hours | Standard Deviation 3.2 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Time to Maximum Plasma Concentration (Tmax) of Ritonavir | 4.5 Hours | Standard Deviation 1.4 |
Secondary
Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay that had a lower limit of detection of 10 IU/mL and a lower limit of quantification (LLOQ) of 25 IU/mL. Complete EVR was defined as HCV RNA levels \< LLOQ (\< 25 IU/mL) at Week 12. Data are reported as the percentage of participants with cEVR.
Time frame: Week 12
Population: To be included in the efficacy analysis, participants received at least one dose of study drug (direct-acting antiviral agent) and have at least one post-baseline measurement of HCV RNA levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | 87.5 percentage of participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | 87.5 percentage of participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | 100.0 percentage of participants |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | 75.0 percentage of participants |
| ABT-072 (300 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | 50.0 percentage of participants |
| ABT-072 (600 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | 85.7 percentage of participants |
| ABT-333 (400 mg) Twice a Day (BID) + pegIFN/RBV | Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | 87.5 percentage of participants |
| ABT-333 (800 mg) Twice Daily (BID) + pegIFN/RBV | Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | 62.5 percentage of participants |
| Placebo + pegIFN/RBV | Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12 | 18.2 percentage of participants |
p-value: 0.005Fisher Exact
p-value: 0.005Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.024Fisher Exact
p-value: 0.319Fisher Exact
p-value: 0.013Fisher Exact
p-value: 0.005Fisher Exact
p-value: 0.074Fisher Exact
Secondary
Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay that had a lower limit of detection of 10 IU/mL and a lower limit of quantification of 25 IU/mL. Partial early virologic response (EVR) was defined as HCV RNA levels that decreased \> 2 log10 IU/mL at Week 12 as compared to baseline. The baseline value was the last measurement before the first dose on Day 1. Data are reported as the percentage of participants with partial EVR.
Time frame: Baseline and Week 12
Population: To be included in the efficacy analysis, participants received at least one dose of study drug (direct-acting antiviral agent) and at least one post-baseline measurement of HCV RNA levels.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | 100.0 percentage of participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | 87.5 percentage of participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | 100.0 percentage of participants |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | 100.0 percentage of participants |
| ABT-072 (300 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | 62.5 percentage of participants |
| ABT-072 (600 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | 100.0 percentage of participants |
| ABT-333 (400 mg) Twice a Day (BID) + pegIFN/RBV | Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | 100.0 percentage of participants |
| ABT-333 (800 mg) Twice Daily (BID) + pegIFN/RBV | Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | 100.0 percentage of participants |
| Placebo + pegIFN/RBV | Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 | 36.4 percentage of participants |
p-value: 0.013Fisher Exact
p-value: 0.059Fisher Exact
p-value: 0.013Fisher Exact
p-value: 0.013Fisher Exact
p-value: 0.37Fisher Exact
p-value: 0.013Fisher Exact
p-value: 0.013Fisher Exact
p-value: 0.013Fisher Exact
Secondary
Percentage of Participants With Rapid Virologic Response (RVR) at Week 4
Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay that had a lower limit of detection of 10 IU/mL and a lower limit of quantification (LLOQ) of 25 IU/mL. Rapid virologic response was defined as HCV RNA level \< LLOQ (\< 25 IU/mL) at Week 4. Data are reported as the percentage of participants with RVR.
Time frame: Week 4
Population: All participants who received at least one dose of study drug and had at least one post-baseline HCV RNA value were included in this efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 87.5 percentage of participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 75.0 percentage of participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 100.0 percentage of participants |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 37.5 percentage of participants |
| ABT-072 (300 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 12.5 percentage of participants |
| ABT-072 (600 mg) Once Daily (QD) + pegIFN/RBV | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 42.9 percentage of participants |
| ABT-333 (400 mg) Twice a Day (BID) + pegIFN/RBV | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 50.0 percentage of participants |
| ABT-333 (800 mg) Twice Daily (BID) + pegIFN/RBV | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 50.0 percentage of participants |
| Placebo + pegIFN/RBV | Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 | 9.1 percentage of participants |
p-value: 0.001Fisher Exact
p-value: 0.006Fisher Exact
p-value: <0.001Fisher Exact
p-value: 0.262Fisher Exact
p-value: 1Fisher Exact
p-value: 0.245Fisher Exact
p-value: 0.111Fisher Exact
p-value: 0.111Fisher Exact
Other Pre-specified
Change From Baseline in ED-5D Visual Analog Scale (ED-5D VAS) Score
The ED-5D VAS was a self-rating survey used to capture the current health status of a participant and ranged from 0 (the worst imaginable health state) to 100 (best imaginable health state). Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation.
Time frame: Baseline and Post-treatment Week 24
Population: Participants received at least one dose of study drug (direct-acting antiviral agent) and have both baseline and at least one post-baseline measurement of HCV RNA levels during monotherapy treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in ED-5D Visual Analog Scale (ED-5D VAS) Score | -5.91 units on a scale | Standard Deviation 31.92 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in ED-5D Visual Analog Scale (ED-5D VAS) Score | -2.38 units on a scale | Standard Deviation 29.86 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in ED-5D Visual Analog Scale (ED-5D VAS) Score | 11.18 units on a scale | Standard Deviation 27.19 |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in ED-5D Visual Analog Scale (ED-5D VAS) Score | -9.00 units on a scale | Standard Deviation 22.23 |
Other Pre-specified
Change From Baseline in EQ-5D (3 Level) Health Index Score
The EQ-5D was a health state questionnaire used to measure five health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). The combination of responses from all five dimensions were derived into an index score ranging from 0 to 1; a higher score indicated a more preferable health utility value from the societal perspectives. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation.
Time frame: Baseline and Post-treatment Week 24
Population: Participants received at least one dose of study drug (direct-acting antiviral agent) and have both baseline and at least one post-baseline measurement of HCV RNA levels during monotherapy treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in EQ-5D (3 Level) Health Index Score | -0.06 units on a scale | Standard Deviation 0.22 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in EQ-5D (3 Level) Health Index Score | -0.06 units on a scale | Standard Deviation 0.15 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in EQ-5D (3 Level) Health Index Score | -0.02 units on a scale | Standard Deviation 0.17 |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in EQ-5D (3 Level) Health Index Score | -0.09 units on a scale | Standard Deviation 0.09 |
Other Pre-specified
Change From Baseline in Hepatitis C Virus Patient-reported Outcomes (HCV-PRO) Total Score
The Hepatitis C Virus Patient-report Outcomes (HCV-PRO, formerly known as HCV Quality of Life) survey was used to assess disease-specific function and well-being on a scale from 0 to 100; a higher score indicated relatively good function and well-being of treated participants. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are reported as the group mean change from baseline ± standard deviation.
Time frame: Baseline up to Post-treatment Week 24
Population: Participants received at least one dose of study drug (direct-acting antiviral agent) and have both baseline and at least one post-baseline measurement of HCV RNA levels during monotherapy treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in Hepatitis C Virus Patient-reported Outcomes (HCV-PRO) Total Score | -0.78 units on a scale | Standard Deviation 15.53 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in Hepatitis C Virus Patient-reported Outcomes (HCV-PRO) Total Score | -0.37 units on a scale | Standard Deviation 13.97 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in Hepatitis C Virus Patient-reported Outcomes (HCV-PRO) Total Score | -3.25 units on a scale | Standard Deviation 14.72 |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in Hepatitis C Virus Patient-reported Outcomes (HCV-PRO) Total Score | -9.04 units on a scale | Standard Deviation 12.41 |
Other Pre-specified
Change From Baseline in SF-36 Mental Component Summary (MCS)
The Mental Component Summary (MCS) of the SF-36 was used to measure the overall mental health status of participants. The aggregated score of the SF-36 MPS was standardized using a linear T-score transformation with a mean of 50 and a standard deviation of 10; a higher score indicated better mental function and well-being. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation.
Time frame: Baseline and Post-treatment Week 24
Population: Participants received at least one dose of study drug (direct-acting antiviral agent) and have both baseline and at least one post-baseline measurement of HCV RNA levels during monotherapy treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in SF-36 Mental Component Summary (MCS) | -2.77 units on a scale | Standard Deviation 5.99 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in SF-36 Mental Component Summary (MCS) | -0.41 units on a scale | Standard Deviation 10.64 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in SF-36 Mental Component Summary (MCS) | -4.37 units on a scale | Standard Deviation 11 |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in SF-36 Mental Component Summary (MCS) | -10.29 units on a scale | Standard Deviation 11.35 |
Other Pre-specified
Change From Baseline in SF-36 Physical Component Summary (PCS)
The Physical Component Summary (PCS) of the SF-36 was used to measure the overall physical health status of a participant. The aggregated score of the SF-36 PCS score was standardized using a linear T-score transformation with a mean of 50 and a standard deviation of 10; a higher score indicated better physical function and well-being. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation.
Time frame: Baseline and Post-treatment Week 24
Population: Participants received at least one dose of study drug (direct-acting antiviral agent) and have both baseline and at least one post-baseline measurement of HCV RNA levels during monotherapy treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in SF-36 Physical Component Summary (PCS) | 3.01 units on a scale | Standard Deviation 6.15 |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in SF-36 Physical Component Summary (PCS) | -1.92 units on a scale | Standard Deviation 5.89 |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in SF-36 Physical Component Summary (PCS) | 4.08 units on a scale | Standard Deviation 5.76 |
| ABT-072 (100 mg) Once Daily (QD) + pegIFN/RBV | Change From Baseline in SF-36 Physical Component Summary (PCS) | -2.84 units on a scale | Standard Deviation 7.92 |
Other Pre-specified
Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B)
Baseline samples were analyzed for resistance-associated amino acid variants using population and clonal sequencing and were compared with the appropriate reference sequence (1a-H77 or 1b-Con1). Phenotypic resistance to ABT-072 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Available samples at Day 4 with HCV RNA ≥ 1000 IU/mL were analyzed for the presence of resistance-associated variants using population and clonal sequencing and were compared with the baseline sequences to assess amino acid changes. Phenotypic resistance to ABT-072 at Day 4 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance are presented.
Time frame: Baseline and Day 4
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the analysis. When the number of participants used to analyze the data at a specific time point differs from the Number of Participants Analyzed, the n (number of participants) is denoted in the Category Title.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Baseline Variants in NS5B | 0 participants |
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Baseline Resistance to ABT-072 >10-fold | 0 participants |
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Day 4: Variants in NS5B (n=6, 7, 6) | 1 participants |
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Day 4: Resistance to ABT-072 >10-fold (n=6, 7, 6) | 0 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Day 4: Resistance to ABT-072 >10-fold (n=6, 7, 6) | 0 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Baseline Variants in NS5B | 1 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Day 4: Variants in NS5B (n=6, 7, 6) | 2 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Baseline Resistance to ABT-072 >10-fold | 1 participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Day 4: Resistance to ABT-072 >10-fold (n=6, 7, 6) | 1 participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Baseline Resistance to ABT-072 >10-fold | 0 participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Day 4: Variants in NS5B (n=6, 7, 6) | 1 participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B) | Baseline Variants in NS5B | 0 participants |
Other Pre-specified
Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B)
Baseline samples were analyzed for resistance-associated amino acid variants using population and clonal sequencing and were compared with the appropriate reference sequence (1a-H77 or 1b-Con1). Phenotypic resistance to ABT-333 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Available samples at Day 4 with HCV RNA ≥ 1000 IU/mL were analyzed for the presence of resistance-associated variants using population and clonal sequencing and were compared with the baseline sequences to assess amino acid changes. Phenotypic resistance to ABT-333 at Day 4 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance are presented.
Time frame: Baseline and Day 4
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the analysis. When the number of participants used to analyze the data at a specific time point differs from the Number of Participants Analyzed, the n (number of participants) is denoted in the Category Title.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B) | Baseline Variants in NS5B | 1 participants |
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B) | Baseline Resistance to ABT-333 >10-fold NS5B | 0 participants |
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B) | Day 4: Variants in NS5B (n=7, 8) | 3 participants |
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B) | Day 4: Resistance to ABT-333 >10-fold (n=7, 8) | 0 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B) | Day 4: Resistance to ABT-333 >10-fold (n=7, 8) | 0 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B) | Baseline Variants in NS5B | 2 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B) | Day 4: Variants in NS5B (n=7, 8) | 3 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B) | Baseline Resistance to ABT-333 >10-fold NS5B | 1 participants |
Other Pre-specified
Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3)
Baseline samples were analyzed for resistance-associated amino acid variants using population and clonal sequencing and were compared with the appropriate reference sequence (1a-H77 or 1b-Con1). Phenotypic resistance to ABT-450 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Available samples at Day 4 with HCV RNA ≥ 1000 IU/mL were analyzed for resistance-associated variants using population and clonal sequencing and were compared with the baseline sequences to assess amino acid changes. Phenotypic resistance to ABT-450 at Day 4 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance are presented.
Time frame: Baseline and Day 4
Population: All participants who received at least one dose of study drug (direct-acting antiviral agent) were included in the analysis. When the number of participants used to analyze the data at a specific time point differs from the Number of Participants Analyzed, the n (number of participants) is denoted in the Category Title.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Baseline Variants in NS3 | 0 participants |
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Baseline Resistance to ABT-450 >10-fold | 0 participants |
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Day 4 Variants in NS3 (n=3, 2, 3) | 2 participants |
| ABT-450/r (50/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Day 4: Resistance to ABT-450 >10-fold (n=3, 2, 3) | 1 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Day 4: Resistance to ABT-450 >10-fold (n=3, 2, 3) | 1 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Baseline Variants in NS3 | 0 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Day 4 Variants in NS3 (n=3, 2, 3) | 2 participants |
| ABT-450/r (100/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Baseline Resistance to ABT-450 >10-fold | 0 participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Day 4: Resistance to ABT-450 >10-fold (n=3, 2, 3) | 0 participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Baseline Resistance to ABT-450 >10-fold | 0 participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Day 4 Variants in NS3 (n=3, 2, 3) | 1 participants |
| ABT-450/r (200/100 mg) Once Daily (QD) + pegIFN/RBV | Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) | Baseline Variants in NS3 | 0 participants |