A Multi-Center, Open-Label, Drug-Drug Interaction Study to Evaluate the Effect of Olutasidenib on the Pharmacokinetics of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and OATP1B1 Substrates in Patients With IDH1 Mutation-Positive Malignancies Being Treated With Olutasidenib
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.
• Adult male or female ≥ 18 years of age at the time of signing the informed consent form
• Must have an Eastern Cooperative Oncology Group performance status ≤ 2.
• Must have recovered from the non-hematologic toxic effects of prior treatment to Grade ≤ 1, or baseline value (excluding infertility, alopecia, or Grade 1 neuropathy)
• Must have a diagnosis of IDH1m+ malignancy to be treated with olutasidenib (e.g. acute myeloid leukemia \[AML\], gastrointestinal \[GI\] cancers, glioma). Patient should not have received olutasidenib within the 2 weeks prior to the first dose of study drug.
• Patient must have an adequate organ function, defined by the following:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values ≤ 2.5 × upper limit of normal (ULN).
• Bilirubin ≤ 1.5× ULN (≤ 3 × ULN in patients with Gilbert Syndrome) or ≤ 3 × ULN for patients with AML involvement.
• Creatinine clearance ≥ 30 mL/min using Cockcroft-Gault equation.
• Female patients who are women of childbearing potential (WOCBP) must have a negative serum (β-hCG) pregnancy test at screening and negative urine test (positive urine tests are to be confirmed by serum test) documented within the 24-hour period prior to the first dose of study drug. WOCBP are defined as sexually mature women without prior hysterectomy or who have had any evidence of menses in the past 12 months. However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, anti-estrogens, or ovarian suppression.
• WOCBP, must agree to use two methods of birth control (e.g. hormonal and a barrier method such as a condom), or must be considered highly unlikely to conceive during the dosing period and for 3 months after last study treatment.
• Male patients with female partners of childbearing potential may be enrolled if they both agree to use highly effective methods of contraception during the dosing period and for 3 months after last study treatment.
• Male patients must refrain from donating sperm during the dosing period and for 3 months after last study treatment.