Clinical trial NCT02857868: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic Impairment
ABL001
Child-Pugh
healthy subjects with normal hepatic function
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-08-05
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Primary Pharmacokinetics (PK): Cmax
timeFrame: at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose
measure: Primary Pharmacokinetics (PK): AUClast
timeFrame: at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose
measure: Primary Pharmacokinetics (PK): AUCinf
timeFrame: at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose
measure: Secondary Pharmacokinetics (PK): Tmax
timeFrame: at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose
measure: Secondary Pharmacokinetics (PK): T 1/2
timeFrame: at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose
measure: Secondary Pharmacokinetics (PK): CL/F
timeFrame: at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose
measure: Secondary Pharmacokinetics (PK): Vz/F
timeFrame: 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:
measure: Percentage of plasma protein binding as expressed by unbound fraction in plasma
timeFrame: 2 hours post-dose
measure: ABL001 pharmacokinetic parameter - Cmax - based on unbound fraction in plasma
timeFrame: 2 hours post-dose
measure: ABL001 pharmacokinetic parameter - AUClast - based on unbound fraction in plasma
timeFrame: 2 hours post-dose
measure: ABL001 pharmacokinetic parameter - AUCinf - based on unbound fraction in plasma
timeFrame: 2 hours post-dose
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami / Clinical Research Services, Inc.
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.