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

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: Asciminib

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1612
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 14050
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Plasma concentration of asciminib by AUClast	The AUC from time zero to the last measurable concentration sampling time (tlast) (ng*h/mL)	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
Pharmacokinetics: Plasma concentration of asciminib by AUCinf	The AUC from time zero to infinity (ng*h/mL)	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
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)	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
Pharmacokinetics: Clearance of asciminib from plasma by CL/F	The total body clearance of drug from the plasma (L/h)	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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
Asciminib PK parameters unbound Cmax (Cmax)u based on unbound fraction in plasma	The observed maximum unbound plasma concentration following administration (ng/mL)	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
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).	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
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)	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
Asciminib secondary PK parameters Vz/F	apparent unbound drug volume of distribution during the terminal elimination phase following extravascular administration	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
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	2 hours post-dose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Hoch M, Sato M, Zack J, Quinlan M, Sengupta T, Allepuz A, Aimone P, Hourcade-Potelleret F. Pharmacokinetics of Asciminib in Individuals With Hepatic or Renal Impairment. J Clin Pharmacol. 2021 Nov;61(11):1454-1465. doi: 10.1002/jcph.1926. Epub 2021 Jul 16.

Helpful Links

• Results for CABL001A2105 can be found on the Novartis Clinical Trial Results Website
• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2018
• Primary Completion (Actual): March 18, 2019
• Study Completion (Actual): April 14, 2019

Study Registration Dates

• First Submitted: July 20, 2018
• First Submitted That Met QC Criteria: July 20, 2018
• First Posted (Actual): July 30, 2018

Study Record Updates

• Last Update Posted (Actual): October 12, 2021
• Last Update Submitted That Met QC Criteria: October 7, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: pharmacokinetics; impaired renal function; ABL001; asciminib
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency
• Other Study ID Numbers: CABL001A2105; 2018-001394-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No