Hepatic Impairment
Conditions
Keywords
Hepatic Impairment, ABL001, Child-Pugh, healthy subjects with normal hepatic function
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.
Interventions
DRUGABL001
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Pharmacokinetics (PK): Vz/F | at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose | 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 | at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose | 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 | at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose | 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 | at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose | 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 | at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose | 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): Cmax | at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose | 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 | at pre- dose (0 hour), 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 72 hours post-dose | 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
| Measure | Time frame | Description |
|---|---|---|
| ABL001 pharmacokinetic parameter - Cmax - based on unbound fraction in plasma | 2 hours post-dose | Unbound fraction I plasma includes but is not limited to unbound Cmax (Cmax) |
| ABL001 pharmacokinetic parameter - AUClast - based on unbound fraction in plasma | 2 hours post-dose | Unbound fraction I plasma includes but is not limited to unbound AUClast (AUClast) |
| ABL001 pharmacokinetic parameter - AUCinf - based on unbound fraction in plasma | 2 hours post-dose | Unbound fraction I plasma includes but is not limited to unbound AUCinf (AUCinf) |
| Percentage of plasma protein binding as expressed by unbound fraction in plasma | 2 hours post-dose | To evaluate ABL001 plasma protein binding |
Countries
United States
Outcome results
None listed