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

NCT03605277 | Completed Phase 1

• 2 other identifiers: CABL001A21052018-001394-25
• Study Type: interventional
• Target: 14
• Locations: 2 countries
• Sites: 2

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.

Conditions

Renal Impairment

Keywords

ABL001; asciminib; impaired renal function; pharmacokinetics

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• 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

• 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

• 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

• 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

• 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

Study Arms (4)

Normal renal function

EXPERIMENTAL

healthy volunteers with normal renal function

Drug: Asciminib

Severe renal impairment

EXPERIMENTAL

subjects with severe renal impairment

Drug: Asciminib

Moderate renal impairment

EXPERIMENTAL

subject with moderate renal impairment

Drug: Asciminib

Mild renal impairment

EXPERIMENTAL

subjects with mild renal impairment

Drug: Asciminib

Interventions

Asciminib DRUG

40 mg single dose

Also known as: ABL001

Mild renal impairment; Moderate renal impairment; Normal renal function; Severe renal impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Sofia, 1612, Bulgaria

Location

Novartis Investigative Site

Berlin, 14050, Germany

Location

Related Publications (1)

• 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.

  PMID: 34115385 DERIVED

Related Links

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

MeSH Terms

Conditions

Renal Insufficiency

Interventions

asciminib

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2018
• First Posted: July 30, 2018
• Study Start: November 16, 2018
• Primary Completion: March 18, 2019
• Study Completion: April 14, 2019
• Last Updated: October 12, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); BU (1)