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

Primary Purpose

Renal Impairment

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Asciminib

About this trial

This is an interventional basic science trial for Renal Impairment focused on measuring ABL001, asciminib, impaired renal function, pharmacokinetics

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Normal renal function

Severe renal impairment

Moderate renal impairment

Mild renal impairment

Arm Description

healthy volunteers with normal renal function

subjects with severe renal impairment

subject with moderate renal impairment

subjects with mild renal impairment

Outcomes

Primary Outcome Measures

Pharmacokinetics: Plasma concentration of asciminib by AUClast

The AUC from time zero to the last measurable concentration sampling time (tlast) (ng*h/mL)

Pharmacokinetics: Plasma concentration of asciminib by AUCinf

The AUC from time zero to infinity (ng*h/mL)

Pharmacokinetics: Plasma concentration of asciminib by Cmax

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

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

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

The observed maximum unbound plasma concentration following administration (ng/mL)

Asciminib secondary PK parameters Tmax, T1/2

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

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

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

asciminib plasma protein binding in subjects with impaired renal function and subjects with normal renal function

Full Information

NCT ID

NCT03605277

First Posted

July 20, 2018

Last Updated

October 7, 2021

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03605277

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2021

Overall Recruitment Status

Completed

Study Start Date

November 16, 2018 (Actual)

Primary Completion Date

March 18, 2019 (Actual)

Study Completion Date

April 14, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Impairment

Keywords

ABL001, asciminib, impaired renal function, pharmacokinetics

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Normal renal function

Arm Type

Experimental

Arm Description

healthy volunteers with normal renal function

Arm Title

Severe renal impairment

Arm Type

Experimental

Arm Description

subjects with severe renal impairment

Arm Title

Moderate renal impairment

Arm Type

Experimental

Arm Description

subject with moderate renal impairment

Arm Title

Mild renal impairment

Arm Type

Experimental

Arm Description

subjects with mild renal impairment

Intervention Type

Drug

Intervention Name(s)

Asciminib

Other Intervention Name(s)

ABL001

Intervention Description

40 mg single dose

Primary Outcome Measure Information:

Title

Pharmacokinetics: Plasma concentration of asciminib by AUClast

Description

The AUC from time zero to the last measurable concentration sampling time (tlast) (ng*h/mL)

Time Frame