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

NCT02857868 | Completed Phase 1 FDA Drug

• 1 other identifier: CABL001A2103
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

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.

Conditions

Hepatic Impairment

Keywords

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

Outcome Measures

Primary Outcomes (7)

• 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

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

• 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

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

• 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

  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 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

  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 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

  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 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

  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 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

  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 Outcomes (4)

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

  2 hours post-dose

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

  2 hours post-dose

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

  2 hours post-dose

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

  2 hours post-dose

Study Arms (1)

ABL001

EXPERIMENTAL

Drug: ABL001

Interventions

ABL001 DRUG

ABL001

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

University of Miami / Clinical Research Services, Inc.

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

DaVita Clinical Research

Minneapolis, Minnesota, 55404, United States

Location

Related Publications (1)

• 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.

  PMID: 34115385 DERIVED

Related Links

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

MeSH Terms

Interventions

asciminib

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2016
• First Posted: August 5, 2016
• Study Start: May 3, 2016
• Primary Completion: July 20, 2017
• Study Completion: July 20, 2017
• Last Updated: December 8, 2020

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)