A Randomized Study to Evaluate the Safety, Tolerability and Antiviral Activity of ABT-450, ABT-333 and ABT-072 (Champion2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01074008
First received: February 22, 2010
Last updated: December 29, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
Hepatitis C
HCV
Chronic Hepatitis C Infection
Hepatitis C Genotype 1
Drug: ABT-450
Drug: ABT-072
Drug: ABT-333
Drug: Ritonavir
Drug: Peginterferon alpha-2a
Drug: Ribavirin
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Blinded, Randomized, Placebo-controlled, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-450 With Ritonavir (ABT-450/r), ABT-333 or ABT-072 Each Administered Alone and in Combination With Peginterferon α-2a and Ribavirin (PegIFN/RBV) in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment [ Time Frame: Prior to dosing on Day 1 to before the morning dose on Day 4 ] [ Designated as safety issue: No ]
    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.

  • Maximum Plasma Concentration (Cmax) of ABT-450 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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 [ 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) ] [ Designated as safety issue: No ]
    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.

  • Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC12) Post-dose of ABT-333 [ 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With Rapid Virologic Response (RVR) at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3) [ Time Frame: Baseline and Day 4 ] [ Designated as safety issue: No ]
    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-072 in Non-structural Viral Protein 5B (NS5B) [ Time Frame: Baseline and Day 4 ] [ Designated as safety issue: No ]
    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-333 in Non-structural Viral Protein 5B (NS5B) [ Time Frame: Baseline and Day 4 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline up to Post-treatment Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in ED-5D Visual Analog Scale (ED-5D VAS) Score [ Time Frame: Baseline and Post-treatment Week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Post-treatment Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Post-treatment Week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and Post-treatment Week 24 ] [ Designated as safety issue: No ]
    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.


Enrollment: 74
Study Start Date: March 2010
Study Completion Date: January 2012
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: ABT-450
50 mg capsules co-administered with ritonavir
Drug: Ritonavir
100 mg capsules co-administered with ABT-450
Other Names:
  • ABT-538
  • Norvir
Drug: Peginterferon alpha-2a
Syringe, 180 µg/0.5 mL for subcutaneous injections
Drug: Ribavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: 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.
Drug: ABT-450
50 mg capsules co-administered with ritonavir
Drug: Ritonavir
100 mg capsules co-administered with ABT-450
Other Names:
  • ABT-538
  • Norvir
Drug: Peginterferon alpha-2a
Syringe, 180 µg/0.5 mL for subcutaneous injections
Drug: Ribavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: 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.
Drug: ABT-450
50 mg capsules co-administered with ritonavir
Drug: Ritonavir
100 mg capsules co-administered with ABT-450
Other Names:
  • ABT-538
  • Norvir
Drug: Peginterferon alpha-2a
Syringe, 180 µg/0.5 mL for subcutaneous injections
Drug: Ribavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: 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.
Drug: ABT-072
50 mg tablet
Drug: Peginterferon alpha-2a
Syringe, 180 µg/0.5 mL for subcutaneous injections
Drug: Ribavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: 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.
Drug: ABT-072
50 mg tablet
Drug: Peginterferon alpha-2a
Syringe, 180 µg/0.5 mL for subcutaneous injections
Drug: Ribavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: 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.
Drug: ABT-072
50 mg tablet
Drug: Peginterferon alpha-2a
Syringe, 180 µg/0.5 mL for subcutaneous injections
Drug: Ribavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: 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.
Drug: ABT-333
400 mg tablet
Other Name: Dasabuvir
Drug: Peginterferon alpha-2a
Syringe, 180 µg/0.5 mL for subcutaneous injections
Drug: Ribavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: 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.
Drug: ABT-333
400 mg tablet
Other Name: Dasabuvir
Drug: Peginterferon alpha-2a
Syringe, 180 µg/0.5 mL for subcutaneous injections
Drug: Ribavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Placebo Comparator: 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.
Drug: Peginterferon alpha-2a
Syringe, 180 µg/0.5 mL for subcutaneous injections
Drug: Ribavirin
200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Other: Placebo
Matching placebo for ABT-450/r, ABT-072, or ABT-333 monotherapy at each dose level

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01074008

  Show 26 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Daniel Cohen AbbVie
  More Information

Additional Information:
No publications provided by AbbVie

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01074008     History of Changes
Other Study ID Numbers: M11-602
Study First Received: February 22, 2010
Results First Received: December 29, 2014
Last Updated: December 29, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Peginterferon alfa-2a
Ribavirin
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on March 31, 2015