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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: Asciminib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Normal renal function<br>healthy volunteers with normal renal function | Drug: Asciminib<br>* 40 mg single dose<br>* Other names: ABL001;|
| Experimental: Severe renal impairment<br>subjects with severe renal impairment | Drug: Asciminib<br>* 40 mg single dose<br>* Other names: ABL001;|
| Experimental: Moderate renal impairment<br>subject with moderate renal impairment | Drug: Asciminib<br>* 40 mg single dose<br>* Other names: ABL001;|
| Experimental: Mild renal impairment<br>subjects with mild renal impairment | Drug: Asciminib<br>* 40 mg single dose<br>* Other names: ABL001;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABL001, asciminib, impaired renal function, pharmacokinetics