The purpose of this study is to evaluate the effect of the following index inhibitors or inducers of CYP2C8 and/or CYP3A on the single-dose pharmacokinetics (PK) of ozanimod and its major active metabolite, CC112273, in healthy adult subjects: gemfibrozil (strong inhibitor of CYP2C8), rifampin (moderate inducer of CYP2C8 and strong inducer of CYP3A), and itraconazole (strong inhibitor of CYP3A). Study Design This is a Phase 1, randomized, parallel-group, open-label study with two parts, 1 and 2. Forty subjects will be enrolled in Part 1 and will be randomized into 1 of the 2 treatment groups, with 20 subjects in each treatment group. Sixty subjects will be enrolled in Part 2 and will be randomized into 1 of the 3 treatment groups, with 20 subjects in each treatment group. . Study parts and treatment groups are as follow: Part 1: * Treatment Group A (reference): A single dose of ozanimod. * Treatment Group B (test): Gemfibrozil 600 mg twice daily (BID) on Days 1 through 17. On Day 4, a single dose of ozanimod will be coadministered with the morning dose of gemfibrozil. Part 2: * Treatment Group C (reference): A single dose of ozanimod. * Treatment Group D (test): Itraconazole 200 mg once daily (QD) on Days 1 through 17. On Day 4, a single dose of ozanimod will be coadministered with itraconazole. * Treatment Group E (test): Rifampin 600 mg QD on Days 1 through 21. On Day 8, a single dose of ozanimod will be coadministered with rifampin. Study Population Subjects will be healthy men and non-pregnant, non-lactating women, ages 18 to 55 years, inclusive, with a body weight of at least 110 pounds (50 kg); body mass index (BMI) within the range of 18.0 to 30.0 kg/m2, inclusive. Length of Study The study duration ranges from 43 days to 50 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
100
PPD Phase 1 Clinic
Austin, Texas, United States
Pharmacokinetics- Cmax
Maximum observed plasma concentration
Time frame: Up to 14 days after ozanimod dosing
Pharmacokinetics- AUC∞
Area under the concentration-time curve from time 0 to infinity
Time frame: Up to 14 days after ozanimod dosing
Pharmacokinetics- AUC0-14d
Area under the concentration-time curve from time 0 to 14 days post dose
Time frame: Up to 14 days after ozanimod dosing
Adverse Events (AEs)
The incidence, severity, and relationship of TEAEs
Time frame: From enrollment until at least 75 days after ozanimod dosing
Pharmacokinetics- Tmax
Time to Cmax
Time frame: Up to 14 days after ozanimod dosing
Pharmacokinetics- CL/F
Apparent oral clearance
Time frame: Up to 14 days after ozanimod dosing
Pharmacokinetics- Vz/F
Apparent volume of distribution during terminal phase after oral administration
Time frame: Up to 14 days after ozanimod dosing
Pharmacokinetics- λz
Terminal elimination rate constant
Time frame: Up to 14 days after ozanimod dosing
Pharmacokinetics- t1/2
Terminal elimination half-life
Time frame: Up to 14 days after ozanimod dosing
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