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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02857868
• Other study ID #: CABL001A2103
• Status: Completed
• Phase: Phase 1
• Start date: May 3, 2016
• Est. completion date: July 20, 2017

Study information

• Verified date: July 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 20, 2017
• Est. primary completion date: July 20, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• ABL001

Locations

Country	Name	City	State
United States	University of Miami / Clinical Research Services, Inc.	Miami	Florida
United States	DaVita Clinical Research	Minneapolis	Minnesota
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	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
Primary	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
Primary	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
Primary	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
Primary	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	Percentage of plasma protein binding as expressed by unbound fraction in plasma	To evaluate ABL001 plasma protein binding	2 hours post-dose
Secondary	ABL001 pharmacokinetic parameter - Cmax - based on unbound fraction in plasma	Unbound fraction I plasma includes but is not limited to unbound Cmax (Cmax)	2 hours post-dose
Secondary	ABL001 pharmacokinetic parameter - AUClast - based on unbound fraction in plasma	Unbound fraction I plasma includes but is not limited to unbound AUClast (AUClast)	2 hours post-dose
Secondary	ABL001 pharmacokinetic parameter - AUCinf - based on unbound fraction in plasma	Unbound fraction I plasma includes but is not limited to unbound AUCinf (AUCinf)	2 hours post-dose

External Links

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