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A Trial to Evaluate the Pharmacokinetics of ABL001 in Healthy and Hepatic Impaired Subjects

Primary Purpose

Hepatic Impairment

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

ABL001

About this trial

This is an interventional treatment trial for Hepatic Impairment focused on measuring Hepatic Impairment, ABL001, Child-Pugh, healthy subjects with normal hepatic function

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Key Inclusion criteria:

Body mass index of 18-36 kg/m2, with body weight 50 kg and no more than 120 kg
Vital signs (after at least 3 minutes rest in the supine position) within the following ranges (inclusive):
- Oral body temperature between 35.0 °C - 37.5 °C (95.0-99.5°F)
- Systolic BP ≥90 mmHg and ≤140 mmHg
- Diastolic BP ≥60 mmHg and ≤90 mmHg for healthy subjects and 50-100 mmHg for subjects with impaired hepatic function (groups 2-4)
- Pulse Rate: ≥50 and ≤90 bpm for healthy subjects (group 1) and ≥50 and ≤100 bpm for subjects with impaired hepatic function (groups 2-4)
Healthy subjects with no clinically significant abnormalities as determined by past medical history, physical examination, vital signs, ECG, and clinical laboratory test
Subjects with Child-Pugh Clinical Assessment Score as calculated per the Child-Pugh classification

Key Exclusion Criteria:

Presence of clinically significant ECG abnormalities or a family history or presence of prolonged QT-interval syndrome
History of cardiac disease
Sexually active males must use a condom during intercourse while taking the drug and for 7 days after stopping
Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs
Administration of strong or moderate CYP3A4 inhibitors or inducers (including St John's wort) within 14 days prior to dosing

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

University of Miami / Clinical Research Services, Inc.
Orlando Clinical Research Center
DaVita Clinical Research

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ABL001

Arm Description

Outcomes

Primary Outcome Measures

Primary Pharmacokinetics (PK): Cmax

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Primary Pharmacokinetics (PK): AUClast

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Primary Pharmacokinetics (PK): AUCinf

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Secondary Pharmacokinetics (PK): Tmax

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Secondary Pharmacokinetics (PK): T 1/2

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Secondary Pharmacokinetics (PK): CL/F

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Secondary Pharmacokinetics (PK): Vz/F

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Secondary Outcome Measures

Percentage of plasma protein binding as expressed by unbound fraction in plasma

To evaluate ABL001 plasma protein binding

ABL001 pharmacokinetic parameter - Cmax - based on unbound fraction in plasma

Unbound fraction I plasma includes but is not limited to unbound Cmax (Cmax)

ABL001 pharmacokinetic parameter - AUClast - based on unbound fraction in plasma

Unbound fraction I plasma includes but is not limited to unbound AUClast (AUClast)

ABL001 pharmacokinetic parameter - AUCinf - based on unbound fraction in plasma

Unbound fraction I plasma includes but is not limited to unbound AUCinf (AUCinf)

Full Information

NCT ID

NCT02857868

First Posted

April 27, 2016

Last Updated

December 6, 2020

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02857868

Brief Title

A Trial to Evaluate the Pharmacokinetics of ABL001 in Healthy and Hepatic Impaired Subjects

Official Title

A Phase I, Open-label, Multi-center, Single-dose Study to Evaluate the Pharmacokinetics of ABL001 in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

May 3, 2016 (Actual)

Primary Completion Date

July 20, 2017 (Actual)

Study Completion Date

July 20, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The main purpose of this study is to evaluate the effect of varying degrees of impaired hepatic function (by Child-Pugh classification) on the pharmacokinetics (PK) of ABL001 after a single oral dose.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatic Impairment

Keywords

Hepatic Impairment, ABL001, Child-Pugh, healthy subjects with normal hepatic function

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ABL001

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

ABL001

Primary Outcome Measure Information:

Title

Primary Pharmacokinetics (PK): Cmax

Description

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Time Frame

at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose

Title

Primary Pharmacokinetics (PK): AUClast

Description

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Time Frame

at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose

Title

Primary Pharmacokinetics (PK): AUCinf

Description

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Time Frame

at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose

Title

Secondary Pharmacokinetics (PK): Tmax

Description

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Time Frame

at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose

Title

Secondary Pharmacokinetics (PK): T 1/2

Description

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Time Frame

at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose

Title

Secondary Pharmacokinetics (PK): CL/F

Description

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Time Frame

at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose

Title

Secondary Pharmacokinetics (PK): Vz/F

Description

To evaluate the pharmacokinetics of a single oral dose of ABL001 in subjects with various degrees of impaired hepatic function (by Child-Pugh classification) relative to healthy subjects

Time Frame

at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose

Secondary Outcome Measure Information:

Title

Percentage of plasma protein binding as expressed by unbound fraction in plasma

Description

To evaluate ABL001 plasma protein binding

Time Frame

2 hours post-dose

Title

ABL001 pharmacokinetic parameter - Cmax - based on unbound fraction in plasma

Description

Unbound fraction I plasma includes but is not limited to unbound Cmax (Cmax)

Time Frame

2 hours post-dose

Title

ABL001 pharmacokinetic parameter - AUClast - based on unbound fraction in plasma

Description

Unbound fraction I plasma includes but is not limited to unbound AUClast (AUClast)

Time Frame

2 hours post-dose

Title

ABL001 pharmacokinetic parameter - AUCinf - based on unbound fraction in plasma

Description

Unbound fraction I plasma includes but is not limited to unbound AUCinf (AUCinf)

Time Frame

2 hours post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion criteria: Body mass index of 18-36 kg/m2, with body weight 50 kg and no more than 120 kg Vital signs (after at least 3 minutes rest in the supine position) within the following ranges (inclusive): Oral body temperature between 35.0 °C - 37.5 °C (95.0-99.5°F) Systolic BP ≥90 mmHg and ≤140 mmHg Diastolic BP ≥60 mmHg and ≤90 mmHg for healthy subjects and 50-100 mmHg for subjects with impaired hepatic function (groups 2-4) Pulse Rate: ≥50 and ≤90 bpm for healthy subjects (group 1) and ≥50 and ≤100 bpm for subjects with impaired hepatic function (groups 2-4) Healthy subjects with no clinically significant abnormalities as determined by past medical history, physical examination, vital signs, ECG, and clinical laboratory test Subjects with Child-Pugh Clinical Assessment Score as calculated per the Child-Pugh classification Key Exclusion Criteria: Presence of clinically significant ECG abnormalities or a family history or presence of prolonged QT-interval syndrome History of cardiac disease Sexually active males must use a condom during intercourse while taking the drug and for 7 days after stopping Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs Administration of strong or moderate CYP3A4 inhibitors or inducers (including St John's wort) within 14 days prior to dosing Other protocol-defined inclusion/exclusion criteria may apply.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

University of Miami / Clinical Research Services, Inc.

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Orlando Clinical Research Center

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

Facility Name

DaVita Clinical Research

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55404

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34115385

Citation

Hoch M, Sato M, Zack J, Quinlan M, Sengupta T, Allepuz A, Aimone P, Hourcade-Potelleret F. Pharmacokinetics of Asciminib in Individuals With Hepatic or Renal Impairment. J Clin Pharmacol. 2021 Nov;61(11):1454-1465. doi: 10.1002/jcph.1926. Epub 2021 Jul 16.

Results Reference

derived

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17159

Description

Results for CABL001A2103 can be found on the Novartis Clinical Trial Results Website

Learn more about this trial

A Trial to Evaluate the Pharmacokinetics of ABL001 in Healthy and Hepatic Impaired Subjects

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