Drug-drug Interaction Study of Ozanimod With Pseudoephedrine to Evaluate the Effect on Blood Pressure and Heart Rate

NCT03644576 | Completed Phase 1 FDA Drug

• 2 other identifiers: RPC01-1914U1111-1215-6267
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of ozanimod after repeated dosing on blood pressure and heart rate response to a single-dose administration of pseudoephedrine (PSE) in healthy adult subjects. Study Design This is a Phase 1, randomized, double-blind, placebo-controlled study. Approximately sixty eligible subjects will be enrolled and randomized in a 1:1 fashion with 30 subjects in each treatment group. Subjects will receive placebo or ozanimod once daily (QD) for 30 days. On Day 30, a single oral dose of pseudoephedrine (PSE) 60 mg will be co-administered with placebo or ozanimod. Study Population The study will enroll approximately 60 healthy men and non-pregnant, non-lactating women, ages 18 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. Length of Study The study duration is 65 ± 2 days.

Conditions

Healthy Volunteers

Keywords

Ozanimod; Pseudoephedrine; Healthy Adult Subjects

Outcome Measures

Primary Outcomes (1)

• Cardiovascular analysis

  Day 30 maximum time-matched change from Day 29 in systolic blood pressure (SBP)

  Days 29 and 30

Secondary Outcomes (18)

• Pharmacokinetics- Cmax

  up to 30 days

• Pharmacokinetics- Cmin

  up to 30 days

• Pharmacokinetics- Tmax

  up to 30 days

• Pharmacokinetics- AUC0-24

  up to 30 days

• Pharmacokinetics- Ctrough

  up to 30 days

Study Arms (2)

ozanimod plus Pseudophedrine

EXPERIMENTAL

ozanimod once daily (QD) for 30 days. On Day 30, a single dose of pseudoephedrine 60mg will be co-administered with ozanimod.

Drug: ozanimod; Drug: Pseudoephedrine

ozanimod placebo plus Pseudoephedrine

PLACEBO COMPARATOR

ozanimod placebo once daily (QD) for 30 days. On Day 30, a single dose of pseudoephedrine 60mg will be co-administered with ozanimod placebo.

Drug: Pseudoephedrine; Drug: ozanimod placebo

Interventions

ozanimod DRUG

ozanimod

ozanimod plus Pseudophedrine

Pseudoephedrine DRUG

Pseudoephedrine

ozanimod placebo plus Pseudoephedrine; ozanimod plus Pseudophedrine

ozanimod placebo DRUG

ozanimod placebo

ozanimod placebo plus Pseudoephedrine

Eligibility Criteria

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

You may qualify if:

• Subject is a man or non-pregnant, non-lactating woman, aged 18 to 55 years, inclusive, at the time of signing the informed consent form (ICF).
• Female subjects must meet at least 1 of the following criteria:
• Negative serum pregnancy test at Screening and Day -2 (women of child-bearing potential \[WOCBP\] only).
• Postmenopausal (defined as 2 years after the last period and follicle-stimulating hormone \[FSH\] \> 40 IU/L).
• Received surgical sterilization (eg, bilateral tubal ligation, bilateral oophorectomy, hysterectomy) at least 6 months before Screening with medical records.
• Females of child-bearing potential:
• Must agree to practice a highly effective method of contraception throughout the study until completion of the 75-day Safety Follow-up. 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.
• 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, implantable
• Placement of an intrauterine device or intrauterine hormone-releasing system
• Bilateral tubal occlusion
• Vasectomized partner
• Sexual abstinence
• Male subjects:

You may not qualify if:

• Subject has clinically significant electrocardiogram (ECG) and cardiovascular symptoms at Screening.
• Subject has a presence or history of any abnormality or illness that, in the opinion of the investigator, may affect absorption, distribution, metabolism, or elimination of the study drugs or would limit the subject's ability to participate in and complete this clinical study.
• Subject has a history of clinically significant or unstable vascular disease, or a history of syncope associated with hypotension within the last 2 years or a history of orthostatic hypotension (or SBP decrease of ≥ 20 mmHg 2 minutes after standing compared with supine SBP).
• Subject with a seated pulse rate outside 55 to 90 beats per minute (bpm) at Screening or Day -2.
• Subject with a resting Fridericia-corrected interval between Q and T wave in the heart's electrical cycle (QTcF) \> 450 msec (males) or \> 470 msec (females) or interval from the beginning of the P wave to the beginning of the QRS complex (PR) \> 200 msec at Screening.
• Subject has a history of alcoholism, drug abuse, or addiction within 24 months prior to Screening.
• Subject has a positive serum test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) at Screening.
• Subject has used any tobacco- or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, vape, electronic cigarettes, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 3 months prior to the first dose of IP.
• Subject has consumed any marijuana products within 3 months prior to the first dose of IP.
• Subject has a positive urine drug test including cotinine at Screening or Day -2.
• Subject has a positive alcohol urine or breath test at Screening or Day -2.
• Subject has received any investigational drug within 30 days or 5 times the elimination half-life (if known), whichever is longer, prior to the first dose of IP.
• Subject has used any systemic over-the-counter medication (excluding acetaminophen up to 1 g/day), dietary or herbal supplement (excluding vitamins/multi-vitamins) within 7 days prior to the first dose of IP. St. John's wort must be discontinued at least 28 days prior to the first dose of IP.
• Subject has used any systemic prescription medication (excluding hormonal contraceptives) within 28 days or 5 times the elimination half-life, whichever is longer, prior to the first dose of IP.
• Subject has used any known MAO inhibitors within 90 days prior to the first dose of IP. 16. Subject has a history of allergic reaction to pseudoephedrine or ozanimod.

Sponsors & Collaborators

• Celgene: lead

Study Sites (1)

ICON Early Phase Services

San Antonio, Texas, 78209, United States

Location

Related Publications (1)

• Tran JQ, Zhang P, Walker S, Ghosh A, Syto M, Wang X, Harris S, Palmisano M. Multiple-Dose Pharmacokinetics of Ozanimod and its Major Active Metabolites and the Pharmacodynamic and Pharmacokinetic Interactions with Pseudoephedrine, a Sympathomimetic Agent, in Healthy Subjects. Adv Ther. 2020 Dec;37(12):4944-4958. doi: 10.1007/s12325-020-01500-0. Epub 2020 Oct 6.

  PMID: 33025342 DERIVED

MeSH Terms

Interventions

ozanimod; Pseudoephedrine

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Phenethylamines; Ethylamines

Study Officials

• Jonathan Tran, Pharm.D

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2018
• First Posted: August 23, 2018
• Study Start: July 11, 2018
• Primary Completion: September 12, 2018
• Study Completion: September 12, 2018
• Last Updated: May 30, 2019

Record last verified: 2019-05

Locations

US (1)