Drug-drug Interaction Study of Ozanimod With Tyramine to Evaluate the Effect on Pressor Response
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|ClinicalTrials.gov Identifier: NCT03694119|
Recruitment Status : Recruiting
First Posted : October 3, 2018
Last Update Posted : October 22, 2018
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).
|Condition or disease||Intervention/treatment||Phase|
|Healthy Volunteer||Drug: Phenelzine Drug: Tyramine Drug: Phenelzine placebo Drug: ozanimod placebo Drug: ozanimod||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||92 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Care Provider, Investigator)|
|Primary Purpose:||Basic Science|
|Official Title:||A Phase 1, Randomized, Double-Blind, Placebo- and Positive-Controlled Study to Evaluate the Effect of Ozanimod on Pressor Response to Oral Tyramine in Healthy Adult Subjects|
|Actual Study Start Date :||July 24, 2018|
|Estimated Primary Completion Date :||January 8, 2019|
|Estimated Study Completion Date :||January 8, 2019|
Active Comparator: Phenelzine
Following tyramine challenging in Period 1, eligible subjects randomly assigned to Phenelzine arm are receiving Phenelzine placebo BID plus ozanimod placebo QD from Days 11 to 31, then receiving Phenelzine 15mg BID plus ozanimod placebo QD from Days 32 to 38. Subjects receive second tyramine challenge from Day 39 to up to Day 49
Drug: Phenelzine placebo
Drug: ozanimod placebo
Placebo Comparator: Placebo
Following tyramine challenging in Period 1, eligible subjects randomly assigned to Placebo arm are receiving Phenelzine placebo BID plus ozanimod placebo QD from Days 11 to 38. Subjects receive second tyramine challenge from Day 39 to up to Day 49
Drug: Phenelzine placebo
Drug: ozanimod placebo
Following tyramine challenging in Period 1, eligible subjects randomly assigned to ozanimod arm are receiving Phenelzine placebo BID plus ozanimod 1.84mg QD from Days 11 to 38, including dose escalation days. Subjects receive second tyramine challenge from Day 39 to up to Day 49
Drug: Phenelzine placebo
- Cardiovascular [ Time Frame: Up to approximately day 49 ]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.
- Pharmacokinetics - Cmin [ Time Frame: From day 11 to day 49 ]Minimum observed plasma concentration within the dosing interval (Cmin)
- Pharmacokinetics - Tmax [ Time Frame: From day 11 to day 38 ]Time to Cmax
- Pharmacokinetics - AUC0-24 [ Time Frame: From day 11 to day 38 ]Area under the concentration-time curve from time 0 to 24 hours (AUC0-24)
- Pharmacokinetics - Ctrough [ Time Frame: From day 11 to day 49 ]Pre- dose or trough concentration
- Adverse Events (AEs) [ Time Frame: From enrollment until 7 +/- 2 days after ozanimod dosing ]Number of participants with Adverse Event.
- Cardiovascular Analysis-SBP [ Time Frame: Up to approximately day 49 ]Descriptive summary of systolic blood pressure by period, treatment, day and nominal time (where appropriate)
- Cardiovascular Analysis-DBP [ Time Frame: Up to approximately day 49 ]Descriptive summary of diastolic blood pressure (DBP) by period, treatment, day and nominal time (where appropriate)
- Cardiovascular Analysis-Heart rate [ Time Frame: Up to approximately day 49 ]Descriptive summary of heart rate by period, treatment, day and nominal time (where appropriate)
- Pharmacokinetics - Cmax [ Time Frame: From day 11 to day 38 ]Maximum observed plasma concentration within the dosing interval (Cmax)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03694119
|Contact: Associate Director Clinical Trial Disclosurefirstname.lastname@example.org|
|United States, Texas|
|PPD Phase 1 Clinic||Recruiting|
|Austin, Texas, United States, 78744|
|Study Director:||Jonathan Tran, Pharm.D||Celgene|