This is a Phase 1, randomized, double-blind, placebo-controlled, active-controlled, comparator controlled, multi-dose, parallel-group study divided into three treatment periods and a follow-up period with five treatment groups. This study will be conducted at 1 clinical research unit (CRU) in the United States (US). Period 1 will consist of daily escalating doses of tyramine administered until tyramine pressor response (defined as the tyramine dose required to increase systolic blood pressure by at least 30 mm Hg from the daily defined baseline in 3 consecutive measurements within 4 hours after tyramine dosing) is achieved or Day 7. Participants who achieve tyramine pressor response at tyramine doses \>/= 200mg and \</= 700mg are eligible for continuation into Period 2 and will be randomized accordingly. Depending on the group to which a participant is randomized, participants will receive rasagiline, phenelzine, ozanimod (therapeutic dose), ozanimod (supra-therapeutic dose), or placebo in Period 2. The duration of dosing depends on the group to which a participant is randomized. In Period 3, all participants will undergo a sham tyramine challenge and receive a single dose of tyramine placebo. Participants who do not achieve tyramine pressor response following the sham challenge will continue with the tyramine challenge (ie, tyramine pressor tests) for up to 12 additional days. Participants who receive at least one dose of study drug in Period 2 will participate in a follow-up phase during which 2 follow-up telephone calls will be performed, the last of which will occur approximately 80 to 100 days after the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
128
Local Institution - 001
Anaheim, California, United States
Tyramine Sensitivity Factor (TSF)
The ratio of Tyramine pressor response (Tyr30) in Period 1 over Tyr30 in Period 3.
Time frame: Up to Day 85
Heart Rate (HR)
Will be summarized descriptively by period, treatment group, day, and nominal time (where appropriate) using the per protocol (PP) population.
Time frame: Up to Day 85
Systolic Blood Pressure (SBP)
Will be summarized descriptively by period, treatment group, day, and nominal time (where appropriate) using the per protocol (PP) population.
Time frame: Up to Day 85
Diastolic Blood Pressure (DBP)
Will be summarized descriptively by period, treatment group, day, and nominal time (where appropriate) using the per protocol (PP) population.
Time frame: Up to Day 85
CC112273 Pharmacokinetics: Cmax
Maximum observed plasma concentration within the dosing interval.
Time frame: Up to Day 85
CC112273 Pharmacokinetics: Cmin
Minimum observed plasma concentration within the dosing interval.
Time frame: Up to Day 85
CC112273 Pharmacokinetics: Tmax
Time to Cmax.
Time frame: Up to Day 85
CC112273 Pharmacokinetics: AUC0-24
Area under the concentration-time curve from time 0 to 24 hours.
Time frame: Up to Day 85
CC112273 Pharmacokinetics: Ctrough
Predose or trough concentration.
Time frame: Up to Day 85
CC1084037 Pharmacokinetics: Cmax
Maximum observed plasma concentration within the dosing interval.
Time frame: Up to Day 85
CC1084037 Pharmacokinetics: Cmin
Minimum observed plasma concentration within the dosing interval.
Time frame: Up to Day 85
CC1084037 Pharmacokinetics: Tmax
Time to Cmax.
Time frame: Up to Day 85
CC1084037 Pharmacokinetics: AUC0-24
Area under the concentration-time curve from time 0 to 24 hours.
Time frame: Up to Day 85
CC1084037 Pharmacokinetics: Ctrough
Predose or trough concentration.
Time frame: Up to Day 85
Ozanimod Pharmacokinetics: Cmax
Maximum observed plasma concentration within the dosing interval.
Time frame: Up to Day 85
Ozanimod Pharmacokinetics: Cmin
Minimum observed plasma concentration within the dosing interval.
Time frame: Up to Day 85
Ozanimod Pharmacokinetics: Tmax
Time to Cmax.
Time frame: Up to Day 85
Ozanimod Pharmacokinetics: AUC0-24
Area under the concentration-time curve from time 0 to 24 hours.
Time frame: Up to Day 85
Ozanimod Pharmacokinetics: Ctrough
Predose or trough concentration.
Time frame: Up to Day 85
Pharmacokinetics for tyramine: Cave
Average observed plasma concentration within the dosing interval.
Time frame: Up to Day 85
Incidence of Adverse Events (AEs)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.
Time frame: From screening until at least 90 days after last dose of study treatment (except for participants who discontinue from the study during Period 1 in which case AEs will be recorded from screening until 24 hours after the last dose of tyramine)
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