Pharmacokinetics Study of Asciminib in Subjects With Impaired Renal Function Compared to Matched Healthy Volunteers

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03605277

Collaborator

(none)

Enrollment

Locations

Arms

4.9

Actual Duration (Months)

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to characterize the pharmacokinetics (PK) and safety profile of asciminib following a single oral dose in adult subjects with renal impairment compared to a matched group of healthy subjects with normal renal function.

The results will determine whether or not a dose adjustment should be recommended when treating patients with asciminib who have impaired renal function.

Condition or Disease	Intervention/Treatment	Phase
Renal Impairment	Drug: Asciminib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

A Phase I, Open-label and Single-dose Study to Evaluate the Pharmacokinetics and Safety of a Single 40 mg Oral Dose of ABL001 (Asciminib) in Subjects With Impaired Renal Function Compared to Matched Control Subjects With Normal Renal Function

Actual Study Start Date :

Nov 16, 2018

Actual Primary Completion Date :

Mar 18, 2019

Actual Study Completion Date :

Apr 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Normal renal function healthy volunteers with normal renal function	Drug: Asciminib 40 mg single dose Other Names: ABL001
Experimental: Severe renal impairment subjects with severe renal impairment	Drug: Asciminib 40 mg single dose Other Names: ABL001
Experimental: Moderate renal impairment subject with moderate renal impairment	Drug: Asciminib 40 mg single dose Other Names: ABL001
Experimental: Mild renal impairment subjects with mild renal impairment	Drug: Asciminib 40 mg single dose Other Names: ABL001

Outcome Measures

Primary Outcome Measures

Pharmacokinetics: Plasma concentration of asciminib by AUClast [pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose]
The AUC from time zero to the last measurable concentration sampling time (tlast) (ng*h/mL)
Pharmacokinetics: Plasma concentration of asciminib by AUCinf [pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose]
The AUC from time zero to infinity (ng*h/mL)
Pharmacokinetics: Plasma concentration of asciminib by Cmax [pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose]
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (ng/mL)
Pharmacokinetics: Clearance of asciminib from plasma by CL/F [pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose]
The total body clearance of drug from the plasma (L/h)

Secondary Outcome Measures

Asciminib PK parameters unbound AUClast (AUClast)u and unbound AUCinf (AUCinf)u based on unbound fraction in plasma [pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose]
including but not limited to: (AUClast)u: area under the unbound plasma concentration-time curve calculated to the last quantifiable concentration point (ng*h/mL)), - (AUCinf)u: unbound plasma concentration-time curve extrapolated to infinity. It is calculated as AUCinf ,u= AUClast ,u+ Clast,u/Lambda_z. (ng*h/mL)
Asciminib PK parameters unbound Cmax (Cmax)u based on unbound fraction in plasma [pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose]
The observed maximum unbound plasma concentration following administration (ng/mL)
Asciminib secondary PK parameters Tmax, T1/2 [pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose]
including but not limited to: Tmax: the time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (h) T1/2: the elimination half-life associated with the terminal slope (lz) of a semi logarithmic concentration-time curve (h).
Asciminib secondary PK parameter AUC0-72h [pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose]
The area under the unbound plasma concentration-time curve from time zero to 72 h post-dosing (ng*h/mL)
Asciminib secondary PK parameters Vz/F [pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose]
apparent unbound drug volume of distribution during the terminal elimination phase following extravascular administration
Percentage of participants with plasma protein binding as expressed by unbound fraction in plasma [2 hours post-dose]
asciminib plasma protein binding in subjects with impaired renal function and subjects with normal renal function

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Male or sterile / post-menopausal female
BMI between 18 and 36 kg/m2, body weight greater than or equal to 50 kg and no more than 120 kg
Adequate venous access for blood sampling
For healthy volunteers: subject must be matched to at least one renal impaired subject by age (+/- 10 years), body weight (+/- 20%) and gender
For renal impaired subjects: documented stable renal disease without evidence of progressive decline in renal function (stable renal disease is defined as no significant change, such as, stable aGFR < 90, for 12 weeks prior to study entry)

Exclusion Criteria:

women of child-bearing potential / pregnant / nursing
contraindication or hypersensitivity to any drug or metabolites from similar class as asciminib or to any excipients of the study drug
cardiac or cardiac repolarization abnormality
history of psychiatric illness within the past 2 years
history of acute or chronic pancreatitis
subject on dialysis
smokers (use of tobacco products in the previous 3 months) and not willing to abstain from using tobacco during the study
any surgical or medical condition altering the absorption, distribution, metabolism or excretion of drug
history of immunodeficiency diseases, including a positive Human Immunodeficiency Virus (HIV) test result at screening
chronic infection with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) at screening
donation or loss of 400 mL or more of blood or plasma within 8 weeks prior to dosing or other amount considered to compromise the health of the subject if previous history of anemia exists
use of the following drugs within 28 days prior to dosing: drugs that prolong the QT interval; CYP3A4 inhibitors and inducers; BCRP, UGT and PgP inhibitors and inducers

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Sofia		Bulgaria	1612
2	Novartis Investigative Site	Berlin		Germany	14050

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:

NCT03605277

Other Study ID Numbers:

CABL001A2105
2018-001394-25

First Posted:

Jul 30, 2018

Last Update Posted:

Oct 12, 2021

Last Verified:

Oct 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Novartis Pharmaceuticals

ABL001

asciminib

impaired renal function

pharmacokinetics

Additional relevant MeSH terms:

Renal Insufficiency

Study Results

No Results Posted as of Oct 12, 2021