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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Hepatic Impairment

Intervention / Treatment
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* Drug: ABL001


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABL001<br> | Drug: ABL001<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of plasma protein binding as expressed by unbound fraction in plasma | To evaluate ABL001 plasma protein binding | 2 hours post-dose | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatic Impairment, ABL001, Child-Pugh, healthy subjects with normal hepatic function