Drug-drug Interaction Study of Ozanimod With Tyramine to Evaluate the Effect on Pressor Response
Condition: Healthy Volunteer
Study type: Interventional
Phase: Phase 1

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 receive IPs (active and/or placebo) twice daily (BID) depending on
      the randomization. Subjects randomized to the phenelzine group will receive phenelzine 15 mg
      BID for 7 days from Days 32 to 38. Subjects randomized to the ozanimod group will receive
      ozanimod 1.84 mg once daily (QD) for 28 days (including the initial 10-day dose escalation).

      Subjects randomized to the placebo group will receive placebos for 28 days. Placebos will be
      matched to phenelzine or ozanimod in appearance to blind the study.

      Period 3: Upon completion of Period 2, subjects in all three treatment groups will undergo a
      second Tyr30 test for up to 11 days. Tyramine challenge in Period 3 will remain blinded since
      phenelzine group has different tyramine dose schedules.

      Study Population The study will enroll approximately 92 healthy men and non-pregnant,
      non-lactating women, ages 25 to 55 years, inclusive, with a body weight of at least 110
      pounds (50 kg) and body mass index within the range of 18.0 to 30.0 kg/m2, inclusive. This is
      to ensure a total of 69 subjects with Tyr30 ≥ 200 mg and ≤ 800 mg at the end of Period 1 to
      be randomized and to allow approximately 54 subjects (18 subjects per group) to complete all
      three periods. A minimum of 30% of each sex will be randomized into each treatment group.

      Length of Study The study duration is up to 84 ± 2 days (including a 28-day Screening period,
      Period 1 of up to 10 days, Period 2 of 28 days, Period 3 of up to 11 days, and a follow-up
      period up through 7 ± 2 days after the last dose of IP).
    


Intervention name(s): Phenelzine; Tyramine; Phenelzine placebo; ozanimod placebo; ozanimod
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Phenelzine; Tyramine; Phenelzine placebo; ozanimod placebo; ozanimod
Intervention MeSH terms: Phenelzine; Ozanimod; Tyramine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Healthy Volunteer; Ozanimod; Oral Tyramine