A open-label drug-drug interaction (DDI) study to evaluate the effects of olutasidenib on the pharmacokinetics (PK) of a CYP450 and OATP1B1 probe substrate cocktail in participants with IDH1 mutation-positive malignancies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
16
Participants will receive repeated dosing of olutasidenib from Day 5 to Day 22 until steady state, with an option to continue treatment up to Day 64
Participants will receive a single dose of each probe substrate on Day 1 and Day 18.
UCI Irvine Health
Orange, California, United States
RECRUITINGNew York Presbyterian Hospital-Columbia University Medical Center
New York, New York, United States
NOT_YET_RECRUITINGArea Under the Plasma Concentration-Time Curve (AUC) of Probe Drugs
To evaluate how olutasidenib affects the overall exposure of several test drugs (probe substrates) that are used to measure the activity of certain enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4) and a drug transporter (OATP1B1). This will be assessed by measuring the area under the plasma concentration-time curve after the probe drugs are taken alone and again after treatment with olutasidenib.
Time frame: Up to 96 hours after each probe drug administration.
Maximum Plasma Concentration (Cmax) of Probe Drugs
To evaluate how olutasidenib affects the peak levels of probe drugs in the blood after they are taken alone and again after treatment with olutasidenib.
Time frame: Up to 96 hours after each probe drug administration.
Time to Maximum Plasma Concentration (Tmax) of Probe Drugs
To assess how olutasidenib affects the time required to reach peak plasma concentration for each probe drug.
Time frame: Up to 96 hours after each probe drug administration
Elimination Half-Life (t½) of Probe Drugs
To evaluate the effect of olutasidenib on the terminal elimination half-life of each probe drug.
Time frame: Up to 96 hours after each probe drug administration
Percent of Area Under the Curve Extrapolated (%AUCex) of Probe Drugs
To determine the proportion of the AUC that is extrapolated, providing insight into olutasidenib's effect on drug elimination.
Time frame: Up to 96 hours after each probe drug administration
Elimination Rate Constant (λz) of Probe Drugs
To assess how olutasidenib affects the terminal elimination rate constant of each probe drug.
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Time frame: Up to 96 hours after each probe drug administration
Apparent Total Body Clearance (CL/F) of Probe Drugs
To evaluate the effect of olutasidenib on the apparent total body clearance of each probe drug.
Time frame: Up to 96 hours after each probe drug administration
Apparent Volume of Distribution (Vz/F) of Probe Drugs
To assess how olutasidenib influences the apparent volume of distribution of each probe drug.
Time frame: Up to 96 hours after each probe drug administration
Incidence, Frequency, and Severity of Treatment-Emergent Adverse Events (TEAEs) with Olutasidenib and Probe Substrates
To assess the safety and tolerability of olutasidenib co-administered with a cocktail of drugs metabolized/transported by CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4, or transported by OATP1B1
Time frame: From the start of treatment through approximately 30 days after the last dose of study treatment