Study to Evaluate the Pressor Effect of Oral Tyramine During Ozanimod Treatment in Healthy Adult Participants

NCT04978298 | Completed Phase 1 FDA Drug

• 1 other identifier: RPC-1063-CP-005
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Volunteers

Keywords

Healthy Volunteers; Phase 1

Outcome Measures

Primary Outcomes (1)

• Tyramine Sensitivity Factor (TSF)

  The ratio of Tyramine pressor response (Tyr30) in Period 1 over Tyr30 in Period 3.

  Up to Day 85

Secondary Outcomes (20)

• Heart Rate (HR)

  Up to Day 85

• Systolic Blood Pressure (SBP)

  Up to Day 85

• Diastolic Blood Pressure (DBP)

  Up to Day 85

• CC112273 Pharmacokinetics: Cmax

  Up to Day 85

• CC112273 Pharmacokinetics: Cmin

  Up to Day 85

Study Arms (5)

Rasagiline group

EXPERIMENTAL

Participants will receive rasagiline once daily (QD) for 14 days from Days 59 to 72.

Other: Placebo; Drug: Rasigiline

Phenelzine group

EXPERIMENTAL

Participants will receive phenelzine twice daily (BID) for 14 days from Days 59 to 72.

Other: Placebo; Drug: Phenelzine

Ozanimod Therapeutic group

EXPERIMENTAL

Participants will receive ozanimod QD for 65 days (including the initial 7-day dose escalation) from Days 8 to 72.

Other: Placebo; Drug: Ozanimod

Ozanimod Supra-therapeutic group

EXPERIMENTAL

Participants will receive ozanimod QD for 65 days (including the initial 10-day dose escalation) from Days 8 to 72.

Other: Placebo; Drug: Ozanimod

Placebo

PLACEBO COMPARATOR

Participants will receive matched appropriate placebos from Days 8 to 72.

Other: Placebo

Interventions

Placebo OTHER

Placebo

Ozanimod Supra-therapeutic group; Ozanimod Therapeutic group; Phenelzine group; Placebo; Rasagiline group

Rasigiline DRUG

Rasigiline

Rasagiline group

Phenelzine DRUG

Phenelzine

Phenelzine group

Ozanimod DRUG

Ozanimod

Ozanimod Supra-therapeutic group; Ozanimod Therapeutic group

Eligibility Criteria

• Age: 25 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must satisfy the following criteria to be enrolled in the study:
• Be a male or non-pregnant, non-lactating female, 25 to 55 years of age, inclusive, at the time of signing the informed consent form.
• Must understand and voluntarily sign an informed consent form prior to any study-related assessments/procedures being conducted.
• Is willing and able to adhere to the study visit schedule and other protocol requirements.
• Female participant must meet at least 1 of the following criteria:
• Have a negative serum pregnancy test at Screening and Day -1 (females of child-bearing potential only).
• Be postmenopausal (defined as 2 years after the last period and follicle-stimulating hormone \> 40 IU/L).
• Have received surgical sterilization (eg, bilateral tubal ligation, bilateral oophorectomy, hysterectomy) at least 6 months before Screening.
• Female of child-bearing potential:
• Must agree to practice a highly effective method of contraception at least 28 days prior to first dose of investigational product until completion of the 90-day safety follow-up period. Highly effective methods of contraception are those that alone or in combination result in a failure rate of a Pearl index of less than 1% per year when used consistently and correctly.
• Examples of acceptable methods of birth control in this study are the following:
• Combined hormonal (estrogen and progestogen containing) contraception, which may be oral, intravaginal, or transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation, which may be oral, injectable, or implantable
• Placement of an intrauterine device or intrauterine hormone-releasing system
• Bilateral tubal occlusion

You may not qualify if:

• The presence of any of the following will exclude a participant from enrollment:
• an unstable SBP (ie, SBP exceeds a maximum range of 15 mm Hg between the lowest and highest values in three consecutive measurements within 15 minutes during Screening).
• the presence or history of any clinically relevant abnormality, condition, or disease (such as glaucoma, liver disease or abnormal liver function tests, cardiovascular or pulmonary diseases) that, in the opinion of the Investigator, may affect absorption, distribution, metabolism, or elimination of the IPs, that would prevent the participant from participating in the study, or which places the participant at unacceptable risk if he/she were to participate in the study.
• any condition that confounds the ability to interpret data from the study.
• history of bipolar, depression or suicidal ideation or behavior, or a history of psychiatric illnesses.
• history of clinically significant or unstable vascular disease, a history of syncope associated with hypotension within the last 2 years, a history of orthostatic hypotension (ie, SBP decrease of \> 20 mm Hg between 2 and 5 minutes after standing compared with supine SBP), or a history of tachycardia or hypertension.
• an estimated glomerular filtration rate (eGFR) \< 80 mL/min/1.73 m2 according to the 2009 chronic kidney disease (CKD) epidemiology collaboration (CKD EPI) equation: eGFR = 141 × min(Scr/κ, 1) × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018 \[if female\] × 1.159 \[if African American\] where: Scr is serum creatinine in mg/dL, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1.
• a seated heart rate outside 55 to 95 beats per minute at Screening or Day -1.
• a resting QTcF \> 450 msec (males) or \> 470 msec (females) or PR interval \> 210 msec at Screening or Day -1 or at additional risk for QT interval prolongation.
• a history of diabetes mellitus type 1, or uncontrolled diabetes mellitus type 2 with hemoglobin A1c (HbA1c) \> 8%.
• a history of uveitis (within the last year prior to Screening) or clinically confirmed diagnosis of macular edema.
• a history of alcoholism, drug abuse, or addiction within 24 months prior to Screening.
• a known active bacterial, viral, fungal (excluding fungal infection of nail beds, minor upper respiratory tract infections, and minor skin infections), mycobacterial infection (including tuberculosis or atypical mycobacterial disease) or any major episode of infection that required hospitalization or treatment with intravenous antibiotics within 30 days of Screening or oral antibiotics within 14 days of Screening.
• In the case of prior SARS-CoV-2 infection, symptoms must have completely resolved and based on Investigator assessment in consultation with the Medical Monitor, there are no sequelae that would place the participant at a higher risk of receiving investigational treatment.
• a positive serum test for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus .

Sponsors & Collaborators

• Celgene: lead

Study Sites (1)

Local Institution - 001

Anaheim, California, 92801, United States

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

MeSH Terms

Interventions

Phenelzine; ozanimod

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals

Study Officials

• Massimo Attanasio, MD

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2021
• First Posted: July 27, 2021
• Study Start: July 19, 2021
• Primary Completion: February 26, 2023
• Study Completion: February 26, 2023
• Last Updated: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (1)