Clinical trial NCT02442258: Pharmacokinetics and Safety of ABT-493 and ABT-530 in Subjects With Normal and Impaired Renal Function
Official title: Evaluation of the Pharmacokinetics and Safety of ABT-493 and ABT-530 in Subjects With Normal and Impaired Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: Renal Impairment
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2015-05-13
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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).

Eligibility criteria: 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.

Primary outcomes:
measure: (SUB-STUDY 1) Area under the plasma concentration-time curve (AUC) from time 0 to infinity for the ABT-493 study drug.
timeFrame: 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.
measure: Overall measurement of safety parameters
timeFrame: SUB-STUDY 1 - Duration of 14 days SUB-STUDY 2 - Duration of 16 Days
measure: Number of subjects with adverse events
timeFrame: Up to 30 days
measure: Maximum plasma concentration (Cmax) of the ABT-493 study drug.
timeFrame: (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.
measure: Area under the plasma concentration-time curve (AUC) for the ABT-493 study drug.
timeFrame: (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.
measure: (SUB-STUDY 1) Area under the plasma concentration-time curve (AUC) from time 0 to infinity for the ABT-530 study drug.
timeFrame: 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.
measure: Maximum plasma concentration (Cmax) of the ABT-530 study drug.
timeFrame: (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.
measure: Area under the plasma concentration-time curve (AUC) for the ABT-530 study drug.
timeFrame: (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.
measure: (SUB-STUDY 2) Area under the plasma concentration-time curve (AUC) during hemodialysis for the ABT-493 study drug.
timeFrame: 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.
measure: (SUB-STUDY 2) Area under the plasma concentration-time curve (AUC) during hemodialysis for the ABT-530 study drug.
timeFrame: 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.
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Site Reference ID/Investigator# 132890
state: Florida
city: Orlando
country: United States
facility: Site Reference ID/Investigator# 132889
state: Florida
city: Grafton, Auckland
country: New Zealand
facility: Site Reference ID/Investigator# 137332
Study officials:
affiliation: AbbVie
name: David Pugatch, MD
role: STUDY_DIRECTOR
References:
citation: Kosloski MP, Zhao W, Marbury TC, Preston RA, Collins MG, Pugatch D, Mensa F, Kort J, Liu W. Effects of Renal Impairment and Hemodialysis on the Pharmacokinetics and Safety of the Glecaprevir and Pibrentasvir Combination in Hepatitis C Virus-Negative Subjects. Antimicrob Agents Chemother. 2018 Feb 23;62(3):e01990-17. doi: 10.1128/AAC.01990-17. Print 2018 Mar.