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

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ClinicalTrials.gov Identifier: NCT03644576
Recruitment Status : Recruiting
First Posted : August 23, 2018
Last Update Posted : October 1, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

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.


Condition or disease Intervention/treatment Phase
Healthy Volunteers Drug: ozanimod Drug: Pseudoephedrine Drug: ozanimod placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 1, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Ozanimod on Blood Pressure and Heart Rate Response to Pseudoephedrine in Healthy Adult Subjects
Actual Study Start Date : July 11, 2018
Estimated Primary Completion Date : December 3, 2018
Estimated Study Completion Date : February 12, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ozanimod plus Pseudophedrine
ozanimod once daily (QD) for 30 days. On Day 30, a single dose of pseudoephedrine 60mg will be co-administered with ozanimod.
Drug: ozanimod
ozanimod

Drug: Pseudoephedrine
Pseudoephedrine

Placebo Comparator: ozanimod placebo plus Pseudoephedrine
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
Pseudoephedrine

Drug: ozanimod placebo
ozanimod placebo




Primary Outcome Measures :
  1. Cardiovascular analysis [ Time Frame: Days 29 and 30 ]
    Day 30 maximum time-matched change from Day 29 in systolic blood pressure (SBP)


Secondary Outcome Measures :
  1. Pharmacokinetics- Cmax [ Time Frame: up to 30 days ]
    Maximum observed plasma concentration within dosing interval on Days 1, 5, 8, and 28 for ozanimod and its metabolites, and on Day 30 for pseudoephedrine.

  2. Pharmacokinetics- Cmin [ Time Frame: up to 30 days ]
    Minimum observed plasma concentration within the dosing interval

  3. Pharmacokinetics- Tmax [ Time Frame: up to 30 days ]
    Time to Cmax on Days 1, 5, 8, and 28 for ozanimod, and its metabolites, and on Day 30 for pseudoephedrine.

  4. Pharmacokinetics- AUC0-24 [ Time Frame: up to 30 days ]
    Area under the concentration-time curve from time 0 to 24 hours on Days 1, 5, 8, and 28 for ozanimod, its metabolites, total drug and total active drug, and on Day 30 for pseudoephedrine.

  5. Pharmacokinetics- Ctrough [ Time Frame: up to 30 days ]
    Pre- dose or trough concentration for ozanimod and its metabolites on Days 26-30

  6. Adverse events (AEs) [ Time Frame: up to 30 days ]
    Number of participants with adverse events

  7. Pharmacokinetics- % total drug related AUC0-24 for each analyte [ Time Frame: up to 30 days ]
    % total drug related AUC0-24 for ozanimod and each metabolite

  8. Pharmacokinetics- % total active drug related AUC0-24 for each active analyte [ Time Frame: up to 30 days ]
    % total active drug related AUC0-24 for ozanimod and each active metabolite

  9. Cardiovascular analysis for DBP [ Time Frame: Days 29 and 30 ]
    Day 30 maximum time-matched change from Day 29 in diastolic blood pressure (DBP)

  10. Cardiovascular analysis for heart rate [ Time Frame: Days 29 and 30 ]
    Day 30 maximum time-matched change from Day 29 in heart rate (HR)

  11. Cardiovascular analysis for blood pressure [ Time Frame: Days 29 and 30 ]
    Day 30, 24-hour average change from Day 29 24-hour average in Blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)

  12. Cardiovascular analysis for heart rate [ Time Frame: Days 29 and 30 ]
    Day 30, 24-hour average change from Day 29 24-hour average in Heart rate

  13. Cardiovascular analysis for blood pressure [ Time Frame: Days 29 and 30 ]
    Day 29 and Day 30 24-hour average for blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP))

  14. Cardiovascular analysis for heart rate [ Time Frame: Days 29 and 30 ]
    Day 29 and Day 30 24-hour average for heart rate

  15. Cardiovascular analysis for blood pressure [ Time Frame: Days 29 and 30 ]
    Day 30 time-matched changes from Day 29 for blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP))

  16. Cardiovascular analysis for heart rate [ Time Frame: Days 29 and 30 ]
    Day 30 time-matched changes from Day 29 for heart rate

  17. Cardiovascular analysis for blood pressure [ Time Frame: Days 29 and 30 ]
    Observed blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP))

  18. Cardiovascular analysis for Heart Rate [ Time Frame: Days 29 and 30 ]
    Observed heart rate (HR)



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 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).
  2. 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.
  3. 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:

    Must agree to use a latex condom with spermicide during sexual contact with WOCBP while participating in the study and until completion of the 75-day Safety Follow-up.

    All subjects:

    Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together.

  4. Male subjects must agree to refrain from donating sperm during the study and until completion of the 75-day Safety Follow-up.
  5. Subject has a body weight of at least 110 pounds (50 kg); body mass index (BMI) within the range of 18.0 to 30.0 kg/m2, inclusive, at Screening and Day -2.
  6. Subject is in good health, as determined by no clinically significant findings from medical or surgical history, 12-lead ECG, physical examination, clinical laboratory tests, and vital signs.
  7. Subject has a mean systolic blood pressure (SBP) of 90 to 140 mmHg, a diastolic blood pressure (DBP) of 50 to 90 mmHg from three consecutive measurements at Screening and Day -2.
  8. Subject must be able to comprehend and provide written informed consent, and must be able to comply with the requirements of the study, including the study visit schedule and other protocol requirements

Exclusion Criteria:

  1. Subject has clinically significant electrocardiogram (ECG) and cardiovascular symptoms at Screening.
  2. 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.
  3. 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).
  4. Subject with a seated pulse rate outside 55 to 90 beats per minute (bpm) at Screening or Day -2.
  5. 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.
  6. Subject has a history of alcoholism, drug abuse, or addiction within 24 months prior to Screening.
  7. Subject has a positive serum test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) at Screening.
  8. 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.
  9. Subject has consumed any marijuana products within 3 months prior to the first dose of IP.
  10. Subject has a positive urine drug test including cotinine at Screening or Day -2.
  11. Subject has a positive alcohol urine or breath test at Screening or Day -2.
  12. 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.
  13. 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.
  14. 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.
  15. 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.

17. Subject has ingested alcohol within 7 days prior to the first dose of IP. 18. Subject plans or will participate in strenuous physical activities during the 24-hour period prior to the first dose of IP.

19. Subject has poor peripheral venous access. 20. Subject has donated greater than 400 mL of blood within 60 days prior to the first dose of IP.

21. Subject has a history of any medical history that, in the opinion of the investigator, might confound the results of the study or jeopardize the safety or welfare of the subject.


Information from the National Library of Medicine

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): NCT03644576


Contacts
Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
United States, Texas
ICON Early Phase Services, LLC Recruiting
San Antonio, Texas, United States, 78209
Sponsors and Collaborators
Celgene
Investigators
Study Director: Jonathan Tran, Pharm.D Celgene

Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03644576     History of Changes
Other Study ID Numbers: RPC01-1914
U1111-1215-6267 ( Registry Identifier: WHO )
First Posted: August 23, 2018    Key Record Dates
Last Update Posted: October 1, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Celgene:
Ozanimod
Pseudoephedrine
Healthy Adult Subjects

Additional relevant MeSH terms:
Pseudoephedrine
Ephedrine
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Nasal Decongestants
Vasoconstrictor Agents
Central Nervous System Stimulants
Sympathomimetics
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action