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)
• Enrollment: 32
• Locations: 3
• Arm: 1
• Actual Duration (Months): 14.6
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.7

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 Disease	Intervention/Treatment	Phase
Hepatic Impairment	Drug: ABL001	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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	University of Miami / Clinical Research Services, Inc.	Miami	Florida	United States	33136
2	Orlando Clinical Research Center	Orlando	Florida	United States	32809
3	DaVita Clinical Research	Minneapolis	Minnesota	United States	55404

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

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: Hepatic Impairment; ABL001; Child-Pugh; healthy subjects with normal hepatic function
• Additional relevant MeSH terms: Liver Diseases

Study Results

No Results Posted as of Dec 8, 2020