Renal Impairment
Conditions
Keywords
ABL001, asciminib, impaired renal function, pharmacokinetics
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.
Interventions
DRUGAsciminib
40 mg single dose
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Plasma concentration of asciminib by AUClast | 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 | The AUC from time zero to the last measurable concentration sampling time (tlast) (ng\*h/mL) |
| Pharmacokinetics: Plasma concentration of asciminib by AUCinf | 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 | The AUC from time zero to infinity (ng\*h/mL) |
| Pharmacokinetics: Plasma concentration of asciminib by Cmax | 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 | 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 | 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 | The total body clearance of drug from the plasma (L/h) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | apparent unbound drug volume of distribution during the terminal elimination phase following extravascular administration |
| 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 | The observed maximum unbound plasma concentration following administration (ng/mL) |
| Percentage of participants with plasma protein binding as expressed by unbound fraction in plasma | 2 hours post-dose | asciminib plasma protein binding in subjects with impaired renal function and subjects with normal renal function |
| 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 | 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 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 | 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 | 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 | The area under the unbound plasma concentration-time curve from time zero to 72 h post-dosing (ng\*h/mL) |
Countries
Bulgaria, Germany
Outcome results
None listed