Drug-drug Interaction Study of Ozanimod With Tyramine to Evaluate the Effect on Pressor Response

Study Summary

The purpose of this study is to evaluate the potential effect of ozanimod on pressor response when co-administered with oral tyramine in healthy adult subjects. Study Design This is a Phase 1, randomized, double-blind (subjects and study site personnel \[except pharmacist or designee\] are blinded to the treatments until 7 ± 2 days postdose follow-up), placebo- and positive-controlled study. Study design is described below: Subjects will be screened for participation in this study within 28 days prior to dosing in Period 1. Period 1: To exclude subjects with very low or very high sensitivity to tyramine, oral tyramine pressor tests will be performed prior to randomization on all subjects after eligibility has been confirmed at Screening (in the absence of any other investigational product \[IP\] treatment) to determine the pressor response to tyramine. The pressor response, referred to hereafter as Tyr30, is defined as the tyramine dose required to increase systolic blood pressure (SBP) by at least 30 mm Hg from daily defined baseline in three consecutive measurements within 4 hours after tyramine dosing. The test consists of daily administration of escalating doses of tyramine (up to 10 days) until a sustained SBP increase of ≥ 30 mm Hg is observed relative to the daily-defined baseline values. Sustained increase is determined by 3 consecutive SBP measurements within 4 hours after tyramine administration. The daily-defined baseline SBP value is defined as the average of five SBP measurements with approximately 5-minute interval after an initial 10- minute rest in the supine position and within 30 minutes prior to tyramine administration. Only subjects who present Tyr30 ≥ 200 mg and ≤ 800 mg will then be randomized. Subjects will be randomized into one of three treatment groups (phenelzine, ozanimod, or placebo) in a 1:1:1 fashion while stratifying for sex in such a manner that each treatment will have a minimum of 30% of either sex. Period 2: Subjects will re

Primary Outcome

Tyramine sensitivity factor (TSF) is the ratio of Tyr30 in Period 1 over Tyr30 in Period 3. Tyr30 is defined as the tyramine dose required to increase systolic blood pressure (SBP) by at least 30 mm Hg from daily defined baseline in three consecutive measurements within 4 hours after tyramine dosing.

Interventions

• DRUG Phenelzine
• DRUG ozanimod
• DRUG ozanimod placebo
• DRUG Tyramine
• DRUG Phenelzine placebo