Pharmacokinetics and Safety of ABT-493 and ABT-530 in Subjects With Normal and Impaired Renal Function

Study Overview
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Brief Summary
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This is an open-label, single dose study designed to assess the pharmacokinetics and safety of ABT-493 and ABT-530 in subjects with either normal renal function or impaired renal function.

Detailed Description
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Up to 48 subjects will be selected and enrolled according to the subject selection criteria: 8 subjects with mild renal impairment (Group 1), 8 subjects with moderate renal impairment (Group 2), 8 subjects with severe renal impairment (Group 3), 8 subjects with end stage renal disease that are not yet on dialysis (Group 4), 8 healthy subjects with normal renal function (Group 5), and 8 subjects with end stage renal disease on hemodialysis (Group 6).

Official Title
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Evaluation of the Pharmacokinetics and Safety of ABT-493 and ABT-530 in Subjects With Normal and Impaired Renal Function

Conditions
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Renal Impairment

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All Subjects Females must have negative results for pregnancy tests performed: At Screening on a urine specimen, and On a serum sample obtained on Study Day -2 (prior to dosing). Body Mass Index (BMI) is ≥ 18 to ≤ 38 kg/m2, inclusive. Body Weight > 50 kg. Subjects with Normal Renal Function In addition to the main inclusion criteria above for all subjects, the following criteria must be met for subjects with normal renal function enrolled in Group 5: Judged to be in general good health based upon the results of a medical history, physical examination, and 12-lead electrocardiogram (ECG). At screening, estimated GFR (by MDRD equation) should be ≥ 90 mL/min/1.73 m2. Subject with Renal Impairment In addition to the main inclusion criteria for all subjects, the following criteria must be met for all subjects with renal impairment enrolled in Groups 1, 2, 3, 4 and 6: 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. Presence of chronic renal impairment as indicated by medical history and a screening estimated GFR (by MDRD equation) < 90 mL/min/1.73 m2. Subjects with ESRD undergoing hemodialysis should have been receiving dialysis for at least 1 month. 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), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab) or HIV antibodies (HIV Ab). Negative HIV status will be confirmed at Screening and the results will be maintained confidentially by the study site. Subjects on strict vegetarian diet.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - Mild Renal Impairment<br>Subjects with mild renal impairment. eGFR (by MDRD equation) range 60 - 89 mL/min/1.73 m2 as determined at Screening. | Drug: ABT-493<br>* A single dose of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* A single dose of ABT-530 will be given orally in combination with ABT-493.<br>|
| Experimental: Group 2 - Moderate Renal Impairment<br>Subjects with moderate renal impairment. eGFR (by MDRD equation) range 30 - 59 mL/min/1.73 m2 as determined at Screening. | Drug: ABT-493<br>* A single dose of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* A single dose of ABT-530 will be given orally in combination with ABT-493.<br>|
| Experimental: Group 3 - Severe Renal Impairment<br>Subjects with severe renal impairment. eGFR (by MDRD equation) range 15 - 29 mL/min/1.73 m2 as determined at Screening. | Drug: ABT-493<br>* A single dose of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* A single dose of ABT-530 will be given orally in combination with ABT-493.<br>|
| Experimental: Group 4 - End Stage Renal Disease, Not Yet on Dialysis<br>Subjects with end stage renal disease, not yet on dialysis. eGFR (by MDRD equation) range < 15 mL/min/1.73 m2 as determined at Screening. | Drug: ABT-493<br>* A single dose of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* A single dose of ABT-530 will be given orally in combination with ABT-493.<br>|
| Experimental: Group 5 - Normal Renal Function<br>Subjects with normal renal function. eGFR (by MDRD equation) range ≥ 90 mL/min/1.73 m2 as determined at Screening. | Drug: ABT-493<br>* A single dose of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* A single dose of ABT-530 will be given orally in combination with ABT-493.<br>|
| Experimental: Group 6 - End Stage Renal Disease, Requiring Dialysis.<br>Subjects with end stage renal disease, requiring dialysis. eGFR (by MDRD equation) < 15 mL/min/1.73 m2 as determined at Screening. | Drug: ABT-493<br>* A single dose of ABT-493 will be given orally in combination with ABT-530.<br>Drug: ABT-530<br>* A single dose of ABT-530 will be given orally in combination with ABT-493.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| (SUB-STUDY 1) Area under the plasma concentration-time curve (AUC) from time 0 to infinity for the ABT-493 study drug. | The AUC from time 0 to infinity represents the total drug exposure over time. | Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. | 
| Overall measurement of safety parameters | Measurement of safety parameters include physical examinations, clinical laboratory tests, 12-lead ECGs (electrocardiograms) and vital signs. | SUB-STUDY 1 - Duration of 14 days SUB-STUDY 2 - Duration of 16 Days | 
| Number of subjects with adverse events | Total number of subjects with adverse events. | Up to 30 days | 
| Maximum plasma concentration (Cmax) of the ABT-493 study drug. | The peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose. | (SUB-STUDY 1) Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. (SUB-STUDY 2) Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period. | 
| Area under the plasma concentration-time curve (AUC) for the ABT-493 study drug. | AUC reflects the actual body exposure to drug after administration of a dose of the drug. | (SUB-STUDY 1) Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. (SUB-STUDY 2) Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period. | 
| (SUB-STUDY 1) Area under the plasma concentration-time curve (AUC) from time 0 to infinity for the ABT-530 study drug. | The AUC from time 0 to infinity represents the total drug exposure over time. | Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. | 
| Maximum plasma concentration (Cmax) of the ABT-530 study drug. | The peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose. | (SUB-STUDY 1) Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. (SUB-STUDY 2) Prior to dosing (0-hour), 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period. | 
| Area under the plasma concentration-time curve (AUC) for the ABT-530 study drug. | AUC reflects the actual body exposure to drug after administration of a dose of the drug. | (SUB-STUDY 1) Prior to dosing (0-hour), 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, 48, 72, 96 hours and 144 hours after dosing on Study Day 1. (SUB-STUDY 2) Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period. | 
| (SUB-STUDY 2) Area under the plasma concentration-time curve (AUC) during hemodialysis for the ABT-493 study drug. | The AUC during hemodialysis represents the total drug exposure over time. | Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period. Additional samples will be collected at 4, 5, and 6 hours after dosing on Study Day 1 of Period 2 only. | 
| (SUB-STUDY 2) Area under the plasma concentration-time curve (AUC) during hemodialysis for the ABT-530 study drug. | The AUC during hemodialysis represents the total drug exposure over time. | Prior to dosing (0-hour), and at 1, 2, 3, 9, 12, 16, 24 hours after dosing on Study Day 1 of each Period. Additional samples will be collected at 4, 5 and 6 hours after dosing on Study Day 1 of Period 2 only. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal Impairment