Clinical trial NCT03605277: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: ABL001
asciminib
impaired renal function
pharmacokinetics
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-07-30
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics: Plasma concentration of asciminib by AUClast
timeFrame: 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
measure: Pharmacokinetics: Plasma concentration of asciminib by AUCinf
timeFrame: 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
measure: Pharmacokinetics: Plasma concentration of asciminib by Cmax
timeFrame: 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
measure: Pharmacokinetics: Clearance of asciminib from plasma by CL/F
timeFrame: 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:
measure: Asciminib PK parameters unbound AUClast (AUClast)u and unbound AUCinf (AUCinf)u based on unbound fraction in plasma
timeFrame: 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
measure: Asciminib PK parameters unbound Cmax (Cmax)u based on unbound fraction in plasma
timeFrame: 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
measure: Asciminib secondary PK parameters Tmax, T1/2
timeFrame: 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
measure: Asciminib secondary PK parameter AUC0-72h
timeFrame: 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
measure: Asciminib secondary PK parameters Vz/F
timeFrame: 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
measure: Percentage of participants with plasma protein binding as expressed by unbound fraction in plasma
timeFrame: 2 hours post-dose
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.