Clinical trial NCT04211558: A Study to Evaluate the Pharmacokinetics of Single Oral Doses of Ozanimod in Healthy Adult Chinese Subjects
Official title: A Phase 1, Open-Label Study to Evaluate the Pharmacokinetics of Single Oral Doses of Ozanimod in Healthy Adult Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Keywords: Healthy Volunteer
Pharmacokinetics (PK)
Ozanimod
Adult Chinese Subjects
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2019-12-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, open-label, single-dose study. Approximately 24 Chinese healthy adult subjects will be enrolled to receive a single oral dose of ozanimod 0.46 mg or 0.92 mg (12 subjects per dose cohort).

Subjects will be screened for participation within 28 days prior to dosing. Eligible subjects will be admitted to the clinical research unit (CRU) or hospital one day before dosing (Day -1) and will be domiciled until Day 15 (approximately 336 hours after ozanimod dosing). Serial PK blood samples for the measurement of plasma concentrations of ozanimod and active metabolites will be collected predose and up to 336 hours after ozanimod dosing.

Physical examinations,12-lead electrocardiograms (ECGs) and ambulatory ECGs, vital sign measurements,pulmonary function tests (PFTs), and clinical laboratory tests will be performed and adverse events and concomitant medications will be monitored throughout the study to assess safety.

Subjects will be contacted by telephone approximately 30 ± 5 days after dosing for a follow-up safety assessment.


Eligibility criteria: Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

1. Subject is a male or female, ages 18 to 45 years
2. Subject is of Chinese origin; individual currently residing in mainland China who was born in China and has both parents of Chinese descent
3. Female subjects must meet at least 1 of the following criteria:

   * Negative serum pregnancy test at Screening and Day -1
   * Postmenopausal
   * Received surgical sterilization at least 6 months before Screening with medical records.
4. Females of child-bearing potential:

   Must agree to practice a highly effective method of contraception throughout the study until 90 days postdose. 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.

   All subjects:

   Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
5. Subject has a total body weight of at least 50 kg (110 lbs); body mass index (BMI) within the range of 19.0 to 24.0 kg/m2
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 must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
8. Subject is willing and able to adhere to the study visit schedule and other protocol

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

1. Subject with a seated blood pressure outside 90 to 140 mmHg systolic or 50 to 90 mmHg diastolic at Screening or Day -1.
2. Subject with a seated pulse rate outside 55 to 90 bpm at Screening or Day -1.
3. 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 IP(s) or would limit the subject's ability to participate in and complete this clinical study.
4. Subject has a history of alcoholism, drug abuse, or addiction within 24 months prior to Screening.
5. Subject has a positive serum test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
6. Subject has used any tobacco- or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, electronic cigarettes, vape, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) or marijuana (cigarette, joint, vape, edibles, etc) within 3 months prior to dosing of the IP.
7. Subject has a positive urine drug test including cotinine at Screening or Day -1.
8. Subject has a positive alcohol urine or breath test at Screening or Day -1.
9. Subject has received any investigational drug within 30 days or 5 times the elimination half-life (if known), whichever is longer, prior to dosing of the IP.
10. Subject has used any systemic over-the-counter medication (excluding acetaminophen up to 1 g/day), dietary or herbal supplement including traditional Chinese medicine (excluding vitamins/multivitamins) within 14 days prior to the first dose of IP. St. John's wort, naringenin, curcumin/turmeric, passion flower, and quercetin must be discontinued at least 28 days prior to dosing of the IP.
11. 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 dosing of the IP.
12. Subject has ingested alcohol within 7 days prior to dosing of the IP.
13. Subject fails or is unwilling to abstain from strenuous physical activities for at least 24 hours prior to dosing of the IP.
14. Subject has poor peripheral venous access.
15. Subject has donated greater than 400 mL of blood within 60 days prior to dosing of the IP or the subject has accepted a blood transfusion or received blood products.
16. Subject has had surgery within 4 weeks prior to dosing, or plans to have surgery during the study period.
17. Subject has a special diet requirement and cannot follow the CRU's or hospital's standard meal.
18. Subject drink large amounts of tea, coffee and or caffeinated drinks (\>8 cups/day, 1 cup = 250mL) daily.
19. Subject has a history of any medical condition or 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.
20. Subject has history of hypersensitivity or allergic reaction to food or other drugs including S1P receptor modulators.

Primary outcomes:
measure: Pharmacokinetic - Cmax (Ozanimod, CC112273 and CC1084037)
timeFrame: 14 days
measure: Pharmacokinetic - Tmax (Ozanimod, CC112273 and CC1084037)
timeFrame: 14 days
measure: Pharmacokinetic - AUC∞ (Ozanimod)
timeFrame: 14 days
measure: Pharmacokinetic - CL/F (Ozanimod)
timeFrame: 14 days
measure: Pharmacokinetic - Vz/F (Ozanimod)
timeFrame: 14 days
measure: Pharmacokinetic - t1/2 (Ozanimod, CC112273 and CC1084037)
timeFrame: 14 days
measure: Pharmacokinetic - AUClast (CC112273 and CC1084037)
timeFrame: 14 days
measure: Pharmacokinetic - AUC0-14d (CC112273 and CC1084037)
timeFrame: 14 days
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: From consent until 30 days after the last dose of IP
Other outcomes:
Locations:
city: Beijing
country: China
facility: Capital Medical University - Beijing Anzhen Hospital
Study officials:
affiliation: Bristol-Myers Squibb
name: Peijin Zhang, M.D, PhD
role: STUDY_DIRECTOR
References: