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An Open-label, Single Arm, Phase 2 Study to Evaluate ABT-450/r/ABT-267 and ABT-333 With Ribavirin (RBV) in Adults With Genotype 1 HCV Infection Taking Methadone or Buprenorphine

Primary Purpose

Chronic Hepatitis C Infection, Chronic Hepatitis C

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
ABT-450/r/ABT-267
ABT-333
Ribavirin (RBV)
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis C Infection focused on measuring HCV Genotype 1, Hepatitis Genotype 1, Interferon Free, methadone, HCV, Buprenorphine, Hepatitis C, Viekira Pak, paritaprevir, Viekira, ombitasvir, dasabuvir

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile.
  • Chronic HCV infection prior to study enrollment.
  • Screening laboratory result indicating HCV genotype 1-infection.
  • Subject must be treatment naive or previous pegylated interferon/ribavirin treatment experienced.
  • Subjects must be on a stable opioid replacement therapy of methadone or buprenorphine ± naloxone for at least 6 months prior to screening.

Exclusion Criteria:

  • Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab) at screening.
  • Prior therapy with direct acting antiviral agents for the treatment of HCV, including telaprevir and boceprevir.
  • Females who are pregnant or plan to become pregnant, or breastfeeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug.
  • Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of >3 or Ishak score of > 4.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    ABT-450/r/ABT-267 and ABT-333, plus RBV

    Arm Description

    ABT-450/r/ABT-267 (150/100/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; 1,000 mg/day if <75 kg or 1,200 mg/day if ≥75 kg, divided twice daily) for 12 weeks

    Outcomes

    Primary Outcome Measures

    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment
    The percentage of participants with sustained virologic response (plasma hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantification [< LLOQ]) 12 weeks after the last dose of study drug.

    Secondary Outcome Measures

    Percentage of Participants With Virologic Failure During Treatment
    Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment) or fail to suppress (HCV RNA ≥ LLOQ) persistently during treatment with at least 6 weeks [≥ 36 days] of treatment.
    Percentage of Participants With Virologic Relapse Post-treatment
    Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment. Completion of treatment was defined as a study drug duration ≥ 77 days.
    Area Under the Plasma Concentration-time Curve (AUC) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
    Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC24 in ng*hr/mL)] was estimated using noncompartmental analyses. For ABT-450, ritonavir, and ABT-267, the AUC from time 0 to the last measureable concentration (AUCt in ng*hr/mL) was calculated instead of AUC24 due to time deviations at 24 hours. The AUCt values are approximately equivalent to AUC24. For ABT-333, ABT-333 M1, and RBV, the AUC from time 0 to 12 hours (AUC12 in ng*hr/mL) after the morning dose was calculated using the 24-hour concentration as the 12-hour concentration as dosing was twice a day and a 12-hour sample was not collected in this study.
    Maximum Plasma Concentration (Cmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
    Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Maximum plasma concentration (Cmax; measured in ng/mL) was directly determined from the concentration-time data.
    Time to Maximum Plasma Concentration (Tmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
    Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. The time to maximum plasma concentration (Tmax; measured in hours) was directly determined from the concentration-time data.
    Plasma Trough Concentration (Ctrough) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
    Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Minimum plasma concentration (C trough; measured in ng/mL) was directly determined from the concentration-time data.

    Full Information

    First Posted
    May 13, 2013
    Last Updated
    April 30, 2018
    Sponsor
    AbbVie
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01911845
    Brief Title
    An Open-label, Single Arm, Phase 2 Study to Evaluate ABT-450/r/ABT-267 and ABT-333 With Ribavirin (RBV) in Adults With Genotype 1 HCV Infection Taking Methadone or Buprenorphine
    Official Title
    An Open-label, Single-Arm, Phase 2 Study to Evaluate the Combination of ABT-450/r/ABT-267 and ABT-333 Coadministered With Ribavirin (RBV) in Adults With Genotype 1 Hepatitis C Virus (HCV) Infection Taking Methadone or Buprenorphine
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    August 2015
    Overall Recruitment Status
    Completed
    Study Start Date
    April 2013 (undefined)
    Primary Completion Date
    December 2013 (Actual)
    Study Completion Date
    September 2014 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    AbbVie

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the safety and efficacy of ABT-450/ritonavir/ABT-267 (ABT-450/r/ABT-267; ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir) and ABT-333 (also known as dasabuvir) coadministered with ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected adults taking methadone or buprenorphine ± naloxone.
    Detailed Description
    This study consisted of 2 periods: a 12-week treatment period and a 48-week post-treatment period (for all participants who received study drugs). All participants who received at least 1 dose of study drug were to be followed for 48 weeks post-treatment to monitor for safety, HCV RNA, the emergence and/or persistence of resistant viral variants, and assessment of patient-reported outcome (PRO) instruments.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Chronic Hepatitis C Infection, Chronic Hepatitis C
    Keywords
    HCV Genotype 1, Hepatitis Genotype 1, Interferon Free, methadone, HCV, Buprenorphine, Hepatitis C, Viekira Pak, paritaprevir, Viekira, ombitasvir, dasabuvir

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    38 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    ABT-450/r/ABT-267 and ABT-333, plus RBV
    Arm Type
    Experimental
    Arm Description
    ABT-450/r/ABT-267 (150/100/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; 1,000 mg/day if <75 kg or 1,200 mg/day if ≥75 kg, divided twice daily) for 12 weeks
    Intervention Type
    Drug
    Intervention Name(s)
    ABT-450/r/ABT-267
    Other Intervention Name(s)
    ABT-450 also known as paritaprevir; ABT-267 also known as ombitasvir
    Intervention Description
    Tablet; ABT-450 coformulated with ritonavir and ABT-267
    Intervention Type
    Drug
    Intervention Name(s)
    ABT-333
    Other Intervention Name(s)
    dasabuvir
    Intervention Description
    Tablet
    Intervention Type
    Drug
    Intervention Name(s)
    Ribavirin (RBV)
    Intervention Description
    Tablet
    Primary Outcome Measure Information:
    Title
    Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment
    Description
    The percentage of participants with sustained virologic response (plasma hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantification [< LLOQ]) 12 weeks after the last dose of study drug.
    Time Frame
    12 weeks after the last actual dose of study drug
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants With Virologic Failure During Treatment
    Description
    Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment) or fail to suppress (HCV RNA ≥ LLOQ) persistently during treatment with at least 6 weeks [≥ 36 days] of treatment.
    Time Frame
    Baseline (Day 1), and Treatment Weeks 1, 2, 4, 6, 8, 10, and 12
    Title
    Percentage of Participants With Virologic Relapse Post-treatment
    Description
    Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment. Completion of treatment was defined as a study drug duration ≥ 77 days.
    Time Frame
    From the end of treatment through 12 weeks after the last actual dose of study drug
    Title
    Area Under the Plasma Concentration-time Curve (AUC) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
    Description
    Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC24 in ng*hr/mL)] was estimated using noncompartmental analyses. For ABT-450, ritonavir, and ABT-267, the AUC from time 0 to the last measureable concentration (AUCt in ng*hr/mL) was calculated instead of AUC24 due to time deviations at 24 hours. The AUCt values are approximately equivalent to AUC24. For ABT-333, ABT-333 M1, and RBV, the AUC from time 0 to 12 hours (AUC12 in ng*hr/mL) after the morning dose was calculated using the 24-hour concentration as the 12-hour concentration as dosing was twice a day and a 12-hour sample was not collected in this study.
    Time Frame
    Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
    Title
    Maximum Plasma Concentration (Cmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
    Description
    Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and were analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Maximum plasma concentration (Cmax; measured in ng/mL) was directly determined from the concentration-time data.
    Time Frame
    Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
    Title
    Time to Maximum Plasma Concentration (Tmax) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
    Description
    Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. The time to maximum plasma concentration (Tmax; measured in hours) was directly determined from the concentration-time data.
    Time Frame
    Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose
    Title
    Plasma Trough Concentration (Ctrough) for ABT-450, Ritonavir, ABT-267, ABT-333, ABT-333 M1 Metabolite, and Ribavirin
    Description
    Blood samples were collected pre-dose (time 0) and at 2, 4, 6, and 24 hours post-dose at one visit between treatment week 2 and treatment week 12, and analyzed using validated analytical methods. A total of 22/38 participants consented for intensive pharmacokinetic blood sampling. Minimum plasma concentration (C trough; measured in ng/mL) was directly determined from the concentration-time data.
    Time Frame
    Pre-dose (time 0) and 2, 4, 6, and 24 hours post-dose

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile. Chronic HCV infection prior to study enrollment. Screening laboratory result indicating HCV genotype 1-infection. Subject must be treatment naive or previous pegylated interferon/ribavirin treatment experienced. Subjects must be on a stable opioid replacement therapy of methadone or buprenorphine ± naloxone for at least 6 months prior to screening. Exclusion Criteria: Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency virus antibody (HIV Ab) at screening. Prior therapy with direct acting antiviral agents for the treatment of HCV, including telaprevir and boceprevir. Females who are pregnant or plan to become pregnant, or breastfeeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug. Any current or past clinical evidence of cirrhosis such as ascites or esophageal varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of >3 or Ishak score of > 4.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Dan Cohen, MD
    Organizational Affiliation
    AbbVie
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    25839406
    Citation
    Lalezari J, Sullivan JG, Varunok P, Galen E, Kowdley KV, Rustgi V, Aguilar H, Felizarta F, McGovern B, King M, Polepally AR, Cohen DE. Ombitasvir/paritaprevir/r and dasabuvir plus ribavirin in HCV genotype 1-infected patients on methadone or buprenorphine. J Hepatol. 2015 Aug;63(2):364-9. doi: 10.1016/j.jhep.2015.03.029. Epub 2015 Apr 1.
    Results Reference
    result
    Links:
    URL
    http://www.rxabbvie.com
    Description
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    An Open-label, Single Arm, Phase 2 Study to Evaluate ABT-450/r/ABT-267 and ABT-333 With Ribavirin (RBV) in Adults With Genotype 1 HCV Infection Taking Methadone or Buprenorphine

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