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

Phase 1

Completed

• Conditions: Renal Impairment
• Interventions: Drug: ABT-493; Drug: ABT-530

• Registration Number: NCT02442258
• Lead Sponsor: AbbVie

Brief Summary

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

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).

Study Timeline

• Study Start: 2015-03
• Study First Submitted: 2015-05-11
• Study First Submitted QC: 2015-05-11
• Study First Posted: 2015-05-13
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-18
• Last Update Posted: 2016-02-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1 - Mild Renal Impairment	ABT-493	Subjects with mild renal impairment. eGFR (by MDRD equation) range 60 - 89 mL/min/1.73 m2 as determined at Screening.
Group 4 - End Stage Renal Disease, Not Yet on Dialysis	ABT-493	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.
Group 3 - Severe Renal Impairment	ABT-493	Subjects with severe renal impairment. eGFR (by MDRD equation) range 15 - 29 mL/min/1.73 m2 as determined at Screening.
Group 3 - Severe Renal Impairment	ABT-530	Subjects with severe renal impairment. eGFR (by MDRD equation) range 15 - 29 mL/min/1.73 m2 as determined at Screening.
Group 5 - Normal Renal Function	ABT-493	Subjects with normal renal function. eGFR (by MDRD equation) range ≥ 90 mL/min/1.73 m2 as determined at Screening.
Group 2 - Moderate Renal Impairment	ABT-493	Subjects with moderate renal impairment. eGFR (by MDRD equation) range 30 - 59 mL/min/1.73 m2 as determined at Screening.
Group 6 - End Stage Renal Disease, Requiring Dialysis.	ABT-530	Subjects with end stage renal disease, requiring dialysis. eGFR (by MDRD equation) \< 15 mL/min/1.73 m2 as determined at Screening.
Group 1 - Mild Renal Impairment	ABT-530	Subjects with mild renal impairment. eGFR (by MDRD equation) range 60 - 89 mL/min/1.73 m2 as determined at Screening.
Group 4 - End Stage Renal Disease, Not Yet on Dialysis	ABT-530	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.
Group 6 - End Stage Renal Disease, Requiring Dialysis.	ABT-493	Subjects with end stage renal disease, requiring dialysis. eGFR (by MDRD equation) \< 15 mL/min/1.73 m2 as determined at Screening.
Group 2 - Moderate Renal Impairment	ABT-530	Subjects with moderate renal impairment. eGFR (by MDRD equation) range 30 - 59 mL/min/1.73 m2 as determined at Screening.
Group 5 - Normal Renal Function	ABT-530	Subjects with normal renal function. eGFR (by MDRD equation) range ≥ 90 mL/min/1.73 m2 as determined at Screening.

Primary Outcome Measures

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

Trial Locations

Locations (3)

Site Reference ID/Investigator# 132890; 🇺🇸 Miami, Florida, United States

Site Reference ID/Investigator# 137332; 🇳🇿 Grafton, Auckland, New Zealand

Site Reference ID/Investigator# 132889; 🇺🇸 Orlando, Florida, United States