A Phase I, 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 Participants with a Susceptible IDH1 Mutation Being Treated with Olutasidenib
Study Description
This is a multi-center, open-label, drug-drug interaction (DDI) study to evaluate the effects of olutasidenib on the pharmacokinetics (PK) of a CYP1A2 probe substrate (caffeine), a CYP2B6 probe substrate (bupropion), a CYP2C8 probe substrate (montelukast), a CYP2C9 probe substrate (losartan), a CYP2C19 probe substrate (lansoprazole), a CYP3A4 probe substrate (triazolam), and an organic anion transporting polypeptide 1B1 (OATP1B1) probe substrate (pravastatin) administered as a drug cocktail to patients with isocitrate
dehydrogenase 1 (IDH1) mutation-positive (IDH1m+) malignancies being treated with olutasidenib.
Eligibility
Patients must meet the following criteria on screening examination to be eligible to participate in the study:
- Willing and able to participate and comply with all study requirements and to provide signed and dated
written informed consent prior to initiation of any study procedures.
- Adult male or female ≥ 18 years of age at the time of signing the informed consent form (ICF).
- Eastern Cooperative Oncology Group performance status ≤ 2.
- Recovery from the non-hematologic toxic effects of prior treatment to Grade ≤ 1, or baseline value according
to National Cancer Institute (NCI)–Common Terminology Criteria for Adverse Events (CTCAE version 5)
classification (excluding infertility, alopecia, or Grade 1 neuropathy)
- Diagnosis of IDH1m+ malignancy to be treated with olutasidenib (e.g. acute myeloid leukemia [AML],
gastrointestinal [GI] cancers, glioma). Should not have received olutasidenib within the 2 weeks prior to the
first dose of study drug.
- Adequate organ function, defined by the following:
a. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values ≤ 2.5 × upper limit of
normal (ULN).
b. Bilirubin ≤ 1.5× ULN (≤ 3 × ULN in patients with Gilbert Syndrome) or ≤ 3 × ULN for patients with
AML involvement.
c. Creatinine clearance ≥ 30 mL/min using Cockroft-Gault equation.
- Females 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. See Section 10.4 for details of acceptable contraception.
- 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. See
Section 10.4 for details of acceptable contraception and for recommendations for partner.
- Male patients must refrain from donating sperm during the dosing period and for 3 months after last study
treatment.
Patients who exhibit any of the following conditions at screening will not be eligible for admission into the study:
- Female who is pregnant or breastfeeding.
- Active smoker. Those who have ceased smoking > 1 month before the Screening Visit will be allowed.
- Ingestion of alcohol within 72 hours prior to first study drug administration and during the study period.
- Plans to become pregnant or father a child (including ova or sperm donation) while enrolled in this study or
within 3 months after last dose of study drug.
- Known allergy or history of hypersensitivity to study drugs or their excipients.
- Human immunodeficiency virus (HIV) positivity.
- Positive serology for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or by RNA
polymerase chain reaction (PCR) at screening. A negative PCR test overrides a positive serological test.
- Serious infection requiring intravenous or systemic antibiotics within 7 days prior to initiation of study
treatment, or any active infection that, in the opinion of the Investigator, could impact patient's safety
(e.g. COVID-19).
- Receiving treat