Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01563536
Recruitment Status : Completed
First Posted : March 27, 2012
Results First Posted : January 8, 2015
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )

Tracking Information
First Submitted Date  ICMJE January 27, 2012
First Posted Date  ICMJE March 27, 2012
Results First Submitted Date  ICMJE December 29, 2014
Results First Posted Date  ICMJE January 8, 2015
Last Update Posted Date July 2, 2018
Study Start Date  ICMJE February 2012
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 29, 2014)
  • Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1 [ Time Frame: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose) ]
    Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was estimated using noncompartmental analyses.
  • Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1 [ Time Frame: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose) ]
    Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Time of maximum plasma concentration (Tmax; measured in hours) was estimated using noncompartmental analyses.
  • Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1 [ Time Frame: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose) ]
    Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC[24]; measured in ng multiplied by hour/mL) was estimated using noncompartmental analyses.
  • Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3 [ Time Frame: Day 2 (pre-dose) and Day 3 (pre-dose) ]
    Blood samples were collected pre-dose on Day 2 (prior to second dose of ABT-267 monotherapy) and pre-dose on Day 3 (prior to first dose of combination therapy). The samples were analyzed for ABT-267 using validated analytical methods. Pre-dose plasma concentrations on Day 2 and Day 3 (Ctrough, measured in ng/mL) are reported.
  • Number of Participants With Adverse Events (AEs) [ Time Frame: All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks). ]
    An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs), and rated the severity of each event as either: Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening. A serious adverse event was any event that resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention.
  • Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy [ Time Frame: Pre-dose on Days 1, 2, and 3 ]
    The baseline value was the last measurement before the first dose of ABT-267 monotherapy (Day 1). The maximal decrease during monotherapy was the change from baseline to the lowest log10 IU/mL HCV RNA level any time from the first dose of ABT-267 on Day 1 to the last log10 HCV RNA level before the first dose of ABT-267 combination therapy (Study Day 3).
Original Primary Outcome Measures  ICMJE
 (submitted: March 23, 2012)
  • Change in HCV RNA levels during ABT-267 during monotherapy treatment [ Time Frame: Baseline to day 3 ]
    Maximum decrease in HCV RNA levels from baseline
  • Number of subject with adverse events as a measure of safety and tolerability [ Time Frame: Baseline to day 3 ]
    Incidence of SAEs, discontinuations and lab abnormalities
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 29, 2014)
  • Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy [ Time Frame: 12 and 24 weeks after last dose of combination study drug ]
    The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [< LLOQ]) 12 and 24 weeks after the last dose of combination study drug. The LLOQ for the assay was 25 IU/mL.
  • Percentage of Participants With Rapid Virologic Response [ Time Frame: 4 weeks ]
    The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) after 4 weeks of combination therapy.
  • Percentage of Participants With End-of-Treatment Response [ Time Frame: 12 weeks ]
    The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) at the end of combination therapy (12 weeks).
  • Percentage of Participants With Extended Rapid Virologic Response [ Time Frame: Weeks 4 to 12 ]
    The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) at Weeks 4 through 12 of combination therapy.
  • Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy [ Time Frame: Predose on Days 1, 2, and 3 ]
    The relationship between ABT-267 dose, ABT-267 concentration, and response was analyzed as the change in viral load (measured as log10 IU/mL) from baseline (pre-dose on Day 1) to pre-dose on Days 2 and 3. Plasma concentrations of ABT-267 pre-dose on Days 2 and 3 are presented above in 4. Primary Outcome: Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 23, 2012)
  • Number of subject with adverse events as a measure of safety and tolerability [ Time Frame: 60 weeks ]
  • Percentage of subjects with sustained virologic response (SVR) [ Time Frame: Through 24 weeks post treatment ]
    SVR (HCV RNA <LLOQ) measured at post treatment week 12 and week 24
  • Percentage of subjects with Rapid Virologic Response (RVR) [ Time Frame: Through week 4 ]
    HCV RNA < LLOQ at week 4
  • Percentage of subjects with extended Early Virologic Response (eEVR) [ Time Frame: Through week 12 ]
    HCV RNA <LLOQ from week 4 through week 12
  • Percentage of subject with complete Early Virologic Response (cEVR) [ Time Frame: Through week 12 ]
    HCV RNA <LLOQ at week 12
Current Other Pre-specified Outcome Measures
 (submitted: December 29, 2014)
Resistance-Associated Variants and Phenotypic Resistance [ Time Frame: Day 1 Pre-dose (Baseline) and Day 3 Pre-dose ]
Baseline (pre-dose on Day 1) samples were analyzed for resistance-associated amino acid (AA) variants using population sequencing. Phenotypic resistance to ABT-267 at Baseline was assessed by calculating the fold difference in the the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Day 3 samples were analyzed using population sequencing and were compared with the baseline and appropriate prototypic reference sequences to assess AA changes. Phenotypic resistance at Day 3 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 AA positions and phenotypic resistance at Baseline and Day 3 are presented.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
Official Title  ICMJE An Open-Label, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
Brief Summary The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and antiviral activity of multiple, ascending doses of ABT-267 (also known as ombitasvir) administered as two-day monotherapy followed by ABT-267 in combination therapy with other direct-acting antiviral agents (DAAs) ABT-450 with ritonavir (ABT-450/r) and ABT-333 (also known as dasabuvir) plus ribavirin (RBV) in patients with chronic Hepatitis C virus (HCV) infection without cirrhosis.
Detailed Description An open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of ABT-267 as monotherapy for 2 days, followed by ABT-267, ABT-450 with ritonavir (ABT-450/r) and ABT-333 plus ribavirin (RBV) combination therapy for 12 weeks in treatment-naïve, non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. The study included post-treatment follow-up for 48 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis C Infection
Intervention  ICMJE
  • Drug: ABT-267
    Tablet
    Other Name: ombitasvir
  • Drug: ABT-450
    Tablet
  • Drug: ABT-333
    Tablet
    Other Name: dasabuvir
  • Drug: Ritonavir
    Capsule
  • Drug: Ribavirin
    Tablet
Study Arms  ICMJE
  • Experimental: ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV
    ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
    Interventions:
    • Drug: ABT-267
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: Ritonavir
    • Drug: Ribavirin
  • Experimental: ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV
    ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
    Interventions:
    • Drug: ABT-267
    • Drug: ABT-450
    • Drug: ABT-333
    • Drug: Ritonavir
    • Drug: Ribavirin
Publications * Mensing S, Polepally AR, König D, Khatri A, Liu W, Podsadecki TJ, Awni WM, Menon RM, Dutta S. Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Patients with Hepatitis C Virus Genotype 1 Infection: Combined Analysis from 9 Phase 1b/2 Studies. AAPS J. 2016 Jan;18(1):270-80. doi: 10.1208/s12248-015-9846-1. Epub 2015 Nov 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 8, 2013)
12
Original Estimated Enrollment  ICMJE
 (submitted: March 23, 2012)
24
Actual Study Completion Date  ICMJE June 2013
Actual Primary Completion Date April 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female between the age of 18 and 70 years, inclusive, at time of enrollment.
  • Subject has never received antiviral treatment for hepatitis C virus (HCV) infection.
  • Body mass index (BMI) is ≥ 18 to < 38 kg/m^2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
  • Chronic HCV genotype 1-infection for at least 6 months prior to study enrollment.
  • Subject has plasma HCV RNA level > 10,000 IU/mL at screening

Exclusion Criteria:

  • History of severe, life-threatening or other significant sensitivity to any drug.
  • Females who are or plan to become pregnant or breastfeeding or males whose partner is pregnant or planning to become pregnant.
  • Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
  • Positive test result for hepatitis B surface antigen or anti-human immunodeficiency virus (HIV) antibodies.
  • Any current or past clinical evidence of cirrhosis (e.g., ascites, esophageal varices), or a liver biopsy or FibroTest/aspartate aminotransferase to platelet ratio (APRI) or FibroScan® showing cirrhosis or extensive bridging fibrosis.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01563536
Other Study ID Numbers  ICMJE M13-386
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AbbVie ( AbbVie (prior sponsor, Abbott) )
Study Sponsor  ICMJE AbbVie (prior sponsor, Abbott)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Andrew L Campbell, MD AbbVie
PRS Account AbbVie
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP