Drug-drug Interaction Study of Ozanimod With Inhibitor or Inducer of CYP2C8 and/or CYP3A

NCT03624959 | Completed Phase 1 FDA Drug

• 2 other identifiers: RPC01-1912U1111-1215-6965
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of the following index inhibitors or inducers of CYP2C8 and/or CYP3A on the single-dose pharmacokinetics (PK) of ozanimod and its major active metabolite, CC112273, in healthy adult subjects: gemfibrozil (strong inhibitor of CYP2C8), rifampin (moderate inducer of CYP2C8 and strong inducer of CYP3A), and itraconazole (strong inhibitor of CYP3A). Study Design This is a Phase 1, randomized, parallel-group, open-label study with two parts, 1 and 2. Forty subjects will be enrolled in Part 1 and will be randomized into 1 of the 2 treatment groups, with 20 subjects in each treatment group. Sixty subjects will be enrolled in Part 2 and will be randomized into 1 of the 3 treatment groups, with 20 subjects in each treatment group. . Study parts and treatment groups are as follow: Part 1:

• Treatment Group A (reference): A single dose of ozanimod.
• Treatment Group B (test): Gemfibrozil 600 mg twice daily (BID) on Days 1 through 17. On Day 4, a single dose of ozanimod will be coadministered with the morning dose of gemfibrozil. Part 2:
• Treatment Group C (reference): A single dose of ozanimod.
• Treatment Group D (test): Itraconazole 200 mg once daily (QD) on Days 1 through 17. On Day 4, a single dose of ozanimod will be coadministered with itraconazole.
• Treatment Group E (test): Rifampin 600 mg QD on Days 1 through 21. On Day 8, a single dose of ozanimod will be coadministered with rifampin. Study Population Subjects will be 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); body mass index (BMI) within the range of 18.0 to 30.0 kg/m2, inclusive. Length of Study The study duration ranges from 43 days to 50 days.

Conditions

Healthy Volunteer

Keywords

Healthy Volunteer; Cytochrome P450 (CYP); ozanimod

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics- Cmax

  Maximum observed plasma concentration

  Up to 14 days after ozanimod dosing

• Pharmacokinetics- AUC∞

  Area under the concentration-time curve from time 0 to infinity

  Up to 14 days after ozanimod dosing

• Pharmacokinetics- AUC0-14d

  Area under the concentration-time curve from time 0 to 14 days post dose

  Up to 14 days after ozanimod dosing

Secondary Outcomes (6)

• Adverse Events (AEs)

  From enrollment until at least 75 days after ozanimod dosing

• Pharmacokinetics- Tmax

  Up to 14 days after ozanimod dosing

• Pharmacokinetics- CL/F

  Up to 14 days after ozanimod dosing

• Pharmacokinetics- Vz/F

  Up to 14 days after ozanimod dosing

• Pharmacokinetics- λz

  Up to 14 days after ozanimod dosing

Study Arms (5)

Treatment Group A - Ozanimod 0.46mg

EXPERIMENTAL

A single dose of ozanimod 0.46 mg on Day 1

Drug: Ozanimod

Treatment Group B - Ozanimod plus Gemfibrozil

EXPERIMENTAL

Gemfibrozil 600 mg twice daily (BID) on Days 1 through 17. On Day 4, a single dose of ozanimod 0.46 mg will be coadministered with the morning dose of gemfibrozil.

Drug: Ozanimod; Drug: Gemfibrozil

Treatment Group C - Ozanimod 0.92mg

EXPERIMENTAL

A single dose of ozanimod 0.92 mg on Day 1.

Drug: Ozanimod

Treatment Group D - Ozanimod plus Itraconazole

EXPERIMENTAL

Itraconazole 200 mg once daily (QD) on Days 1 through 17. On Day 4, a single dose of ozanimod 0.92 mg will be co-administered with itraconazole.

Drug: Ozanimod; Drug: Itraconazole

Treatment Group E - Ozanimod plus Rifampin

EXPERIMENTAL

Rifampin 600 mg QD on Days 1 through 21. On Day 8, a single dose of ozanimod 0.92 mg will be coadministered with rifampin

Drug: Ozanimod; Drug: Rifampin

Interventions

Ozanimod DRUG

ozanimod

Treatment Group A - Ozanimod 0.46mg; Treatment Group B - Ozanimod plus Gemfibrozil; Treatment Group C - Ozanimod 0.92mg; Treatment Group D - Ozanimod plus Itraconazole; Treatment Group E - Ozanimod plus Rifampin

Gemfibrozil DRUG

Gemfibrozil

Treatment Group B - Ozanimod plus Gemfibrozil

Itraconazole DRUG

Itraconazole

Treatment Group D - Ozanimod plus Itraconazole

Rifampin DRUG

Rifampin

Treatment Group E - Ozanimod plus Rifampin

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, ages 18 to 55 years, inclusive, at the time of signing of the informed consent form (ICF).
• Female subjects must meet at least 1 of the following criteria:
• Negative serum pregnancy test at Screening and Day -1 (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 (oestrogen 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 with a seated blood pressure outside 90 to 140 mmHg systolic or 50 to 90 mmHg diastolic at Screening or Day -1.
• Subject with a seated pulse rate outside 55 to 90 bpm at Screening or Day -1.
• 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 Investigational product (IP) or would limit the subject's ability to participate in and complete this clinical study.
• 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).
• 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.
• Subject has a positive urine drug test including cotinine at Screening or Day -1.
• Subject has a positive alcohol urine or breath test at Screening or Day -1.
• 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/multivitamins) within 7 days prior to the first dose of IP. 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.
• 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 ingested alcohol within 7 days prior to the first dose of IP.
• Subject fails or is unwilling to abstain from strenuous physical activities for at least 24 hours prior to the first dose of IP.
• Subject has poor peripheral venous access.
• Subject has donated greater than 400 mL of blood within 60 days prior to Day 1.

Sponsors & Collaborators

• Celgene: lead

Study Sites (1)

PPD Phase 1 Clinic

Austin, Texas, 78744, United States

Location

Related Publications (1)

• Tran JQ, Zhang P, Ghosh A, Liu L, Syto M, Wang X, Palmisano M. Single-Dose Pharmacokinetics of Ozanimod and its Major Active Metabolites Alone and in Combination with Gemfibrozil, Itraconazole, or Rifampin in Healthy Subjects: A Randomized, Parallel-Group, Open-Label Study. Adv Ther. 2020 Oct;37(10):4381-4395. doi: 10.1007/s12325-020-01473-0. Epub 2020 Aug 28.

  PMID: 32857315 DERIVED

MeSH Terms

Interventions

ozanimod; Gemfibrozil; Itraconazole; Rifampin

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Pentanoic Acids; Valerates; Phenyl Ethers; Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Volatile; Fatty Acids; Lipids; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Jonathan Tran, Pharm.D

  Celgene Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: August 10, 2018
• Study Start: June 20, 2018
• Primary Completion: August 10, 2018
• Study Completion: August 10, 2018
• Last Updated: May 30, 2019

Record last verified: 2019-05

Locations

US (1)