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

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).

Conditions

• Healthy Volunteer

Interventions

DRUG

Phenelzine

Phenelzine

DRUG

Tyramine

Tyramine

DRUG

Phenelzine placebo

Phenelzine placebo

DRUG

ozanimod placebo

ozanimod placebo

DRUG

ozanimod

ozanimod

Sponsors & Collaborators

• Celgene

  lead INDUSTRY

Principal Investigators

• Jonathan Tran, Pharm.D · Celgene

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

25 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-07-24

Primary Completion

2019-01-08

Completion

2019-01-08

FDA Drug

Yes

Countries

• United States

Study Locations