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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02857868
Collaborator
(none)
32
Enrollment
3
Locations
1
Arm
14.6
Actual Duration (Months)
10.7
Patients Per Site
0.7
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
May 3, 2016
Actual Primary Completion Date :
Jul 20, 2017
Actual Study Completion Date :
Jul 20, 2017

Arms and Interventions

ArmIntervention/Treatment
Experimental: ABL001

Drug: ABL001

Outcome Measures

Primary Outcome Measures

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

Secondary Outcome Measures

  1. Percentage of plasma protein binding as expressed by unbound fraction in plasma [2 hours post-dose]

    To evaluate ABL001 plasma protein binding

  2. 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)

  3. 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)

  4. 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)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1University of Miami / Clinical Research Services, Inc.MiamiFloridaUnited States33136
2Orlando Clinical Research CenterOrlandoFloridaUnited States32809
3DaVita Clinical ResearchMinneapolisMinnesotaUnited States55404

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02857868
Other Study ID Numbers:
  • CABL001A2103
First Posted:
Aug 5, 2016
Last Update Posted:
Dec 8, 2020
Last Verified:
Jul 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 8, 2020