Back to resultsPharmacokinetics and Safety of ABT-493 and ABT-530 in Subjects With Normal and Impaired Renal Function
Primary Purpose
Renal Impairment
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
ABT-493
ABT-530
Sponsored by
About this trial
This is an interventional basic science trial for Renal Impairment focused on measuring Renal Impairment
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.
Sites / Locations
- Site Reference ID/Investigator# 132890
- Site Reference ID/Investigator# 132889
- Site Reference ID/Investigator# 137332
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Group 1 - Mild Renal Impairment
Group 2 - Moderate Renal Impairment
Group 3 - Severe Renal Impairment
Group 4 - End Stage Renal Disease, Not Yet on Dialysis
Group 5 - Normal Renal Function
Group 6 - End Stage Renal Disease, Requiring Dialysis.
Arm Description
Subjects with mild renal impairment. eGFR (by MDRD equation) range 60 - 89 mL/min/1.73 m2 as determined at Screening.
Subjects with moderate renal impairment. eGFR (by MDRD equation) range 30 - 59 mL/min/1.73 m2 as determined at Screening.
Subjects with severe renal impairment. eGFR (by MDRD equation) range 15 - 29 mL/min/1.73 m2 as determined at Screening.
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.
Subjects with normal renal function. eGFR (by MDRD equation) range ≥ 90 mL/min/1.73 m2 as determined at Screening.
Subjects with end stage renal disease, requiring dialysis. eGFR (by MDRD equation) < 15 mL/min/1.73 m2 as determined at Screening.
Outcomes
Primary Outcome Measures
(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.
Overall measurement of safety parameters
Measurement of safety parameters include physical examinations, clinical laboratory tests, 12-lead ECGs (electrocardiograms) and vital signs.
Number of subjects with adverse events
Total number of subjects with adverse events.
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.
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) 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.
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.
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 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.
(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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02442258
Brief Title
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
2. Study Status
Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
December 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Impairment
Keywords
Renal Impairment
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1 - Mild Renal Impairment
Arm Type
Experimental
Arm Description
Subjects with mild renal impairment. eGFR (by MDRD equation) range 60 - 89 mL/min/1.73 m2 as determined at Screening.
Arm Title
Group 2 - Moderate Renal Impairment
Arm Type
Experimental
Arm Description
Subjects with moderate renal impairment. eGFR (by MDRD equation) range 30 - 59 mL/min/1.73 m2 as determined at Screening.
Arm Title
Group 3 - Severe Renal Impairment
Arm Type
Experimental
Arm Description
Subjects with severe renal impairment. eGFR (by MDRD equation) range 15 - 29 mL/min/1.73 m2 as determined at Screening.
Arm Title
Group 4 - End Stage Renal Disease, Not Yet on Dialysis
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 5 - Normal Renal Function
Arm Type
Experimental
Arm Description
Subjects with normal renal function. eGFR (by MDRD equation) range ≥ 90 mL/min/1.73 m2 as determined at Screening.
Arm Title
Group 6 - End Stage Renal Disease, Requiring Dialysis.
Arm Type
Experimental
Arm Description
Subjects with end stage renal disease, requiring dialysis. eGFR (by MDRD equation) < 15 mL/min/1.73 m2 as determined at Screening.
Intervention Type
Drug
Intervention Name(s)
ABT-493
Intervention Description
A single dose of ABT-493 will be given orally in combination with ABT-530.
Intervention Type
Drug
Intervention Name(s)
ABT-530
Intervention Description
A single dose of ABT-530 will be given orally in combination with ABT-493.
Primary Outcome Measure Information:
Title
(SUB-STUDY 1) Area under the plasma concentration-time curve (AUC) from time 0 to infinity for the ABT-493 study drug.
Description
The AUC from time 0 to infinity represents the total drug exposure over time.
Time Frame
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.
Title
Overall measurement of safety parameters
Description
Measurement of safety parameters include physical examinations, clinical laboratory tests, 12-lead ECGs (electrocardiograms) and vital signs.
Time Frame
SUB-STUDY 1 - Duration of 14 days SUB-STUDY 2 - Duration of 16 Days
Title
Number of subjects with adverse events
Description
Total number of subjects with adverse events.
Time Frame
Up to 30 days
Title
Maximum plasma concentration (Cmax) of the ABT-493 study drug.
Description
The peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Time Frame
(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.
Title
Area under the plasma concentration-time curve (AUC) for the ABT-493 study drug.
Description
AUC reflects the actual body exposure to drug after administration of a dose of the drug.
Time Frame
(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.
Title
(SUB-STUDY 1) Area under the plasma concentration-time curve (AUC) from time 0 to infinity for the ABT-530 study drug.
Description
The AUC from time 0 to infinity represents the total drug exposure over time.
Time Frame
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.
Title
Maximum plasma concentration (Cmax) of the ABT-530 study drug.
Description
The peak concentration that a drug achieves in a specified compartment after the drug has been administrated and before administration of a second dose.
Time Frame
(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.
Title
Area under the plasma concentration-time curve (AUC) for the ABT-530 study drug.
Description
AUC reflects the actual body exposure to drug after administration of a dose of the drug.
Time Frame
(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.
Title
(SUB-STUDY 2) Area under the plasma concentration-time curve (AUC) during hemodialysis for the ABT-493 study drug.
Description
The AUC during hemodialysis represents the total drug exposure over time.
Time Frame
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.
Title
(SUB-STUDY 2) Area under the plasma concentration-time curve (AUC) during hemodialysis for the ABT-530 study drug.
Description
The AUC during hemodialysis represents the total drug exposure over time.
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Pugatch, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Site Reference ID/Investigator# 132890
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Site Reference ID/Investigator# 132889
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Site Reference ID/Investigator# 137332
City
Grafton, Auckland
ZIP/Postal Code
1010
Country
New Zealand
12. IPD Sharing Statement
Citations:
PubMed Identifier
29263061
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.
Results Reference
derived
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Pharmacokinetics and Safety of ABT-493 and ABT-530 in Subjects With Normal and Impaired Renal Function
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