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

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

Official Title
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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

Conditions
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HCV Infection

Intervention / Treatment
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* Drug: ABT-267
* Drug: Placebo
* Procedure: Blood Sample Collection
* Drug: Cytochrome P450 inhibitor


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Single Ascending Dose (SAD)<br>Healthy volunteers, receiving single ascending doses of ABT-267 or placebo. | Drug: ABT-267<br>* See arm description<br>Drug: Placebo<br>* See arms description<br>|
| Placebo Comparator: Multiple Ascending Dose (MAD)<br>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<br>* See arm description<br>Drug: Placebo<br>* See arms description<br>Drug: Cytochrome P450 inhibitor<br>* See arm description<br>|
| Active Comparator: Food Effect (FE)<br>Healthy volunteers, receiving ABT-267, multi-dose, food effect. | Drug: ABT-267<br>* See arm description<br>|
| Placebo Comparator: Antiviral Activity<br>HCV genotype 1-infected treatment naïve subjects receiving multiple ascending doses of ABT-267 or placebo monotherapy for 3 days. | Drug: ABT-267<br>* See arm description<br>Drug: Placebo<br>* See arms description<br>|
| No Intervention: Resistance Monitoring<br>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<br>* See arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |