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

Hepatic Impairment Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02296905
• Other study ID #: M13-604
• Status: Completed
• Phase: Phase 1
• First received: November 19, 2014
• Last updated: October 20, 2015
• Start date: October 2014
• Est. completion date: September 2015

Study information

• Verified date: October 2015
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationNew Zealand: Ethics Committee
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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:

1. Evidence of liver cirrhosis OR

2. 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• ABT-493
Up to 2 single doses of ABT-493 will be given orally in combination with ABT-530.
• ABT-530
Up to 3 single doses of ABT-530 will be given orally alone or in combination with ABT-493.

Locations

Country	Name	City	State
New Zealand	Site Reference ID/Investigator# 130590	Grafton
United States	Site Reference ID/Investigator# 130589	Miami	Florida
United States	Site Reference ID/Investigator# 130591	Orlando	Florida
United States	Site Reference ID/Investigator# 130588	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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	Yes
Primary	Number of subjects with adverse events		Up to 58 days	Yes