Study of ABT-267 in Both Healthy Volunteers and Hepatitis C Virus (HCV) Genotype 1 Infected Subjects

A Blinded, Randomized, Placebo-Controlled Study in Healthy and HCV Genotype 1-infected Adults, to Evaluate the Safety, Tolerability, Antiviral Activity, Pharmacokinetics (Including the Effect of Food) and Resistance Profile of Single and Multiple Doses of ABT-267

Study of ABT-267 in both healthy volunteers and Hepatitis C virus (HCV) genotype 1 infected subjects.

Study Overview

• Status: Completed
• Conditions: HCV Infection
• Intervention / Treatment: Drug: ABT-267; Drug: Placebo; Drug: Cytochrome P450 inhibitor; Procedure: Blood Sample Collection

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Site Reference ID/Investigator# 42708
  • Illinois
    • Waukegan, Illinois, United States, 60085
      • Site Reference ID/Investigator# 43322
  • Texas
    • San Antonio, Texas, United States, 78215
      • Site Reference ID/Investigator# 42707

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

Main Selection Criteria for Healthy Volunteers:

• Subject has provided written consent.
• Subject is in general good health.
• Females must be post-menopausal for at least 2 years or surgically sterile.
• Females must not be pregnant or breast-feeding. If male, subject is surgically sterile or practicing specific forms of birth control.

Main Selection Criteria for HCV Genotype 1-infected Volunteers:

• Subject has provided written consent.
• Subject has chronic HCV genotype 1 infection at screening.
• Liver biopsy within 3 years with histology.
• Females must be post-menopausal for at least 2 years or surgically sterile.
• Females must not be pregnant or breast-feeding. If male, subject is surgically sterile or practicing specific forms of birth control.
• Subject is in general good health, as perceived by the investigator, other than HCV infection.

Main Selection Criteria for Volunteers in the Resistance Monitoring Portion of the Study:

• Subject has provided written consent, has received at least one dose of ABT-267 or placebo in the study, and is considered suitable by the investigator to participate.

Exclusion Criteria

Main Exclusion Criteria for Healthy Volunteers:

• Positive test for HAV IgM, HBsAg, HCV Ab or HIV Ab.
• Clinically significant cardiovascular, respiratory (except mild asthma), renal, gastrointestinal, hematologic, neurologic, thyroid, or any uncontrolled medical illness or psychiatric disorder.
• Use of tobacco or nicotine-containing products with the 6-month period prior to study drug administration.
• Abnormal screening laboratory results.
• Significant sensitivity to any drug.
• Requirement for any over the counter and/or prescription medication, vitamins and/or herbal supplements on a regular basis.

Main Exclusion Criteria for HCV Genotype 1-infected Volunteers:

• Significant sensitivity to any drug.
• Positive HBsAg, HAV-IgM, and HIV Ab. Use of CYP enzyme inducers or inhibitors within 1 month of dosing.
• Clinically significant cardiovascular, respiratory (except mild asthma), renal, gastrointestinal, hematologic, neurologic, thyroid disease (except hypothyroidism on stable thyroid replacement therapy), or any uncontrolled medical illness or psychiatric disorder.
• Use of any medications (prescription and over-the counter) within 2 weeks prior to study drug dosing without prior approval by the Abbott Medical Monitor.
• Use of any vitamins or herbal supplements within 2 weeks prior to study drug dosing.
• Prior treatment with any investigational or commercially available anti-HCV agents.
• Abnormal screening laboratory results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Single Ascending Dose (SAD); Healthy volunteers, receiving single ascending doses of ABT-267 or placebo.	Drug: ABT-267; See arm description; Drug: Placebo; See arms description
Placebo Comparator: Multiple Ascending Dose (MAD); Healthy volunteers, receiving multiple ascending doses of ABT-267 or placebo, OR, multiple doses of ABT-267 + single dose of a Cytochrome P450 inhibitor or placebo + single dose of a Cytochrome P450 inhibitor.	Drug: ABT-267; See arm description; Drug: Placebo; See arms description; Drug: Cytochrome P450 inhibitor; See arm description
Active Comparator: Food Effect (FE); Healthy volunteers, receiving ABT-267, multi-dose, food effect.	Drug: ABT-267; See arm description
Placebo Comparator: Antiviral Activity; HCV genotype 1-infected treatment naïve subjects receiving multiple ascending doses of ABT-267 or placebo monotherapy for 3 days.	Drug: ABT-267; See arm description; Drug: Placebo; See arms description
No Intervention: Resistance Monitoring; HCV genotype 1-infected treatment naïve subjects, receiving at least one dose of ABT-267 or placebo in the "Antiviral Activity" arm, follow-up to monitor resistance developed to ABT-267, no treatment and only blood samples will be collected	Procedure: Blood Sample Collection; See arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Analysis of pharmacokinetic variables and mean change in HCV RNA level from baseline.	Up to 15 days or less
Analysis of safety measures including but not limited to tabulation of adverse events, physical exam, vital signs, ECGs, continuous cardiac monitoring, and clinical lab results (including chemistry, hematology and urine).	Update to 20 days or less

Collaborators and Investigators

• Sponsor: Abbott

Publications and helpful links

General Publications

• Krishnan P, Beyer J, Mistry N, Koev G, Reisch T, DeGoey D, Kati W, Campbell A, Williams L, Xie W, Setze C, Molla A, Collins C, Pilot-Matias T. In vitro and in vivo antiviral activity and resistance profile of ombitasvir, an inhibitor of hepatitis C virus NS5A. Antimicrob Agents Chemother. 2015 Feb;59(2):979-87. doi: 10.1128/AAC.04226-14. Epub 2014 Dec 1.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: August 12, 2010
• First Submitted That Met QC Criteria: August 12, 2010
• First Posted (Estimate): August 13, 2010

Study Record Updates

• Last Update Posted (Estimate): January 24, 2012
• Last Update Submitted That Met QC Criteria: January 20, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Cytochrome P-450 Enzyme Inhibitors
• Other Study ID Numbers: M12-116