Clinical trial NCT04528290: A Study to Evaluate the Relative Bioavailability of a Pediatric Granule Formulation of Ozanimod in Healthy Adult Subjects
Official title: A Phase 1, Randomized, Parallel-group, Open-label, Single-dose, Relative Bioavailability Study of a Pediatric Granule Formulation of Ozanimod in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Ozanimod
RPC-1063
Pediatric Granule Formulation
Healthy Volunteer
Pharmacokinetics (PK)
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2020-08-27
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This is a Phase 1, open-label, randomized, parallel-group, single-dose study. Approximately 56 participants will be enrolled and randomized into 1 of the 2 treatment groups, with 28 participants in each treatment group as follows:

* Treatment Group A (reference): Current ozanimod capsule formulation
* Treatment Group B (test): Ozanimod granule formulation participants will be screened within 28 days prior to dosing.

Eligible participants will be admitted to the clinical research unit one day before dosing (Day -1) and will be domiciled until Day 15. On Day 1, a single oral dose of 0.92 mg of ozanimod will be administered using either the current capsule formulation (Group A) or the granule formulation (Group B).

Participants will be contacted by telephone 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, ≥ 18 and ≤ 55 years
2. Female subjects must meet at least 1 of the following criteria:

   * Negative serum pregnancy test at Screening and Day -1
   * Postmenopausal
   * Received surgical sterilization
3. Female subjects of child-bearing potential:

   Must agree to practice a highly effective method of contraception throughout the study until completion of the Follow-up phone call.

   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
   * Complete sexual abstinence

   All subjects:

   Periodic abstinence, withdrawal, spermicides only, and lactational amenorrhea method are not acceptable methods of contraception. Female condom and male condom should not be used together.
4. 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
5. 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.
6. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
7. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

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 beats per minute (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 IPs or would limit the subject's ability to participate in and complete this clinical study.
4. Subject has any condition that confounds the ability to interpret data from the study.
5. Subject has a history of alcoholism, drug abuse, or addiction within 24 months prior to Screening.
6. Subject has a positive serum test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).
7. 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 the first dose of IP.
8. Subject has a positive urine drug test including cotinine at Screening or Day -1.
9. Subject has a positive alcohol urine or breath test at Screening or Day -1.
10. 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.
11. Subject has used any systemic over-the-counter medication (excluding acetaminophen up to 1 g/day), dietary or herbal supplement (excluding vitamins/multivitamins) within 7 days prior to the first dose of IP. Herbal supplements including St. John's wort, naringenin, curcurmin/turmeric, passion flower, and quercetin must be discontinued at least 28 days prior to the first dose of IP.
12. Subject has consumed pomelo-variety citrus fruits or juice (including pomelo, grapefruit, Seville oranges) within 7 days prior to the first dose of IP.
13. 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.
14. Subject has ingested alcohol within 7 days prior to the first dose of IP.
15. Subject fails or is unwilling to abstain from strenuous physical activities for at least 24 hours prior to the first dose of IP.
16. Subject has poor peripheral venous access.
17. Subject has donated greater than 400 mL of blood within 60 days prior to Day 1.
18. Subject with 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.
19. Subject has history of hypersensitivity or allergic reaction to S1P receptor modulators.

Primary outcomes:
measure: Pharmacokinetic- Cmax (Ozanimod, CC112273, CC1084037)
timeFrame: Up to 14 days
measure: Pharmacokinetic- AUC∞(Ozanimod)
timeFrame: Up to 14 days
measure: Pharmacokinetic- AUClast (CC112273 and CC1084037)
timeFrame: Up to 14 days
Secondary outcomes:
measure: Adverse Events (AEs)
timeFrame: From enrollment until at least 30 days after last dose of IP
measure: Pharmacokinetic- AUClast (Ozanimod)
timeFrame: Up to 14 days
measure: Pharmacokinetic- Tmax (Ozanimod, CC112273, and CC1084037)
timeFrame: Up to 14 days
measure: Pharmacokinetic- CL/F (Ozanimod)
timeFrame: Up to 14 days
measure: Pharmacokinetic- Vz/F (Ozanimod)
timeFrame: Up to 14 days
measure: Pharmacokinetic- t1/2 (Ozanimod, CC112273, and CC1084037)
timeFrame: Up to 14 days
Other outcomes:
Locations:
city: Austin
country: United States
facility: PPD Phase 1 Clinic
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: