Pharmacokinetics and Safety of ABT-493 and/or ABT-530 in Subjects With Normal and Impaired Hepatic Function

Study Overview
=================
Brief Summary
-----------------
This is an open-label, single-dose study designed to assess the pharmacokinetics and safety of ABT-493 and/or ABT-530 in subjects with impaired hepatic function and compare them to those in subjects with normal hepatic function. Twenty-four subjects will be selected and enrolled according to the subject selection criteria: 6 subjects with mild stable chronic hepatic impairment (Group I), 6 subjects with moderate stable chronic hepatic impairment (Group II), 6 subjects with severe stable chronic hepatic impairment (Group III) and 6 subjects with normal hepatic function (Group IV).

Official Title
-----------------
Pharmacokinetics and Safety of ABT-493 and/or ABT-530 in Subjects With Normal and Impaired Hepatic Function

Conditions
-----------------
Hepatic Impairment

Intervention / Treatment
-----------------
* Drug: ABT-493
* Drug: ABT-530


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All Subjects If female, subject must be either postmenopausal for at least 2 years or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy). Females must have negative results for pregnancy test performed: At Screening on a urine specimen obtained within 28 days prior to initial study drug administration, and On a serum sample obtained on Study Day -1 of Period 1. Males must be surgically sterile or practicing at least one of the following methods of birth control (sperm donation within the study period is not allowed): Abstinence Partner(s) using an Intrauterine Device (IUD) Partner(s) using oral, injected, or implanted methods of hormonal contraceptives Subject and/or partner(s) using double-barrier method. Subjects with Normal Hepatic Function In addition to the inclusion criteria above for all subjects, the following criteria must be met for subjects with normal hepatic function enrolled in Group IV: Judged to be in general good health based upon the results of a medical history, physical examination, laboratory profile (including liver function parameters within the limits of normal) and 12-lead electrocardiogram (ECG). Negative hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCV Ab) test results. Body Mass Index (BMI) is ≥ 18 to < 38 kg/m2, inclusive. Subjects with Hepatic Impairment In addition to the inclusion criteria for all subjects, the following criteria must be met for all subjects with hepatic impairment enrolled in Groups I, II and III: Judged to be in stable condition and acceptable for study participation based upon the results of a medical history, physical examination, laboratory profile and ECG. BMI is ≥ 18 to < 38 kg/m2, inclusive, for subjects with hepatic impairment without ascites or subjects with subclinical ascites detected only by ultrasound or other imaging. For subjects with hepatic impairment and clinically significant ascites, BMI is permitted in the range between ≥ 18 to < 40 kg/m2, inclusive. Child-Pugh classification of Categories A (mild), B (moderate), or C (severe). Medical history of chronic liver disease including and not limited to chronic hepatitis B, history of alcoholic liver disease and chronic hepatitis C. Presence of clinically significant hepatic impairment as indicated by either: Evidence of liver cirrhosis OR Medical history of at least one of the following criteria: Clinical diagnosis of liver disease Total bilirubin, > 2 mg/dl, with indirect/direct ratio < 1 or prolonged prothrombin time elevation > 1.7 or an albumin value below the lower limit of the laboratory reference range and excluding non-hepatic causes of the previous laboratory abnormalities. Exclusion Criteria: - History of significant sensitivity to any drug. Pregnant or breastfeeding female. Recent (6-month) history of drug or alcohol abuse. Positive test result for hepatitis A virus immunoglobulin M (HAV-IgM) or human immunodeficiency virus antibody (HIV Ab). Negative HIV status will be confirmed at Screening and the results will be maintained confidentially by the study site. Detectable HCV RNA.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group I<br>Subjects with mild hepatic impairment | Drug: ABT-493<br>* Up to 2 single doses of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* Up to 3 single doses of ABT-530 will be given orally alone or in combination with ABT-493.<br>|
| Experimental: Group II<br>Subjects with moderate hepatic impairment | Drug: ABT-493<br>* Up to 2 single doses of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* Up to 3 single doses of ABT-530 will be given orally alone or in combination with ABT-493.<br>|
| Experimental: Group III<br>Subjects with severe hepatic impairment | Drug: ABT-493<br>* Up to 2 single doses of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* Up to 3 single doses of ABT-530 will be given orally alone or in combination with ABT-493.<br>|
| Experimental: Group IV<br>Subjects with normal hepatic function | Drug: ABT-493<br>* Up to 2 single doses of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* Up to 3 single doses of ABT-530 will be given orally alone or in combination with ABT-493.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall measurement of pharmacokinetic parameter values of ABT-493 and ABT-530 | Pharmacokinetic parameter values include the maximum plasma concentration (Cmax), the terminal phase elimination rate constant (B), the area under the plasma concentration-time curve (AUC) from time 0 to time of the last measurable concentration (AUCt). | 7 days | 
| Overall measurement of safety parameters | Measurement of safety parameters include physical examinations, clinical laboratory tests, 12-lead ECGs (electrocardiograms) and vital signs. | Up to 38 days | 
| Number of subjects with adverse events |  | Up to 58 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatic Impairment, Hepatitis C Virus Infection