A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild or Moderate Hepatic Impairment on the Multiple-Dose Pharmacokinetics of Ozanimod

NCT04639115 | Completed Phase 1 FDA Drug

• 2 other identifiers: RPC-1063-CP-004U1111-1257-6851
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief Summary

This is a Phase 1, multicenter, nonrandomized, open-label, parallel-group study in participants with mild or moderate hepatic impairment, and in participants with normal hepatic function. Degrees of hepatic impairment will be determined during screening by the participant's score according to Pugh's Modification of Child's Classification of Severity of Liver Disease. Participants will be enrolled in Groups 1 through 3 as follows:

• Group 1 (mild hepatic impairment): A total of approximately 8 participants with a Child-Pugh score of 5 to 6.
• Group 2 (moderate hepatic impairment): A total of approximately 8 participants with a Child-Pugh score of 7 to 9.
• Group 3 (normal hepatic function): Approximately 8 to 16 participants will be matched to Participants in Groups 1 and 2. Normal hepatic function participants are allowed to match multiple hepatic impairment participants. Participants will be matched by sex, age (± 10 years), weight (± 20%), and smoking status.

Conditions

Liver Diseases; Digestive System Diseases

Keywords

Mild and moderate Hepatic impairment; Healthy volunteer; Ozanimod

Outcome Measures

Primary Outcomes (5)

• Pharmacokinetics - AUClast on Day 8 (Ozanimod, CC112273 and CC1084037)

  AUC from time zero to the last measured time point

  Up to day 8

• Pharmacokinetics - AUC∞ on Day 8 (Ozanimod, CC112273 and CC1084037)

  Area under the plasma concentration-time curve from time zero extrapolated to infinity

  Up to day 8

• Pharmacokinetics - Cmax on Day 8 (Ozanimod, CC112273 and CC1084037)

  Maximum observed plasma concentration

  Up to day 8

• Pharmacokinetics - Cmin on Day 8 (Ozanimod, CC112273 and CC1084037)

  Minimum observed plasma concentration

  Up to day 8

• Pharmacokinetics - AUCtau on Day 8 (Ozanimod, CC112273 and CC1084037)

  Area under the plasma concentration-time curve from time zero to dosing interval

  Up to day 8

Secondary Outcomes (15)

• Adverse Events (AEs)

  From the time the ICF is signed until 64 ± 3 days after the last dose of ozanimod treatment

• Pharmacokinetics -Cmax on Days 1 and 5 (Ozanimod, CC112273 and CC1084037)

  Days 1 and 5

• Pharmacokinetics -Cmin on Days 1 and 5 (Ozanimod, CC112273 and CC1084037)

  Days 1, and 5

• Pharmacokinetics - AUCtau on Days 1 and 5 (Ozanimod, CC112273 and CC1084037)

  Days 1 and 5

• Pharmacokinetics - Tmax (Ozanimod, CC112273 and CC1084037)

  Days 1, 5, and 8

Study Arms (3)

Ozanimod in subjects with mild hepatic impairment

EXPERIMENTAL

Participants will receive ozanimod 0.23 mg once daily (QD) on Days 1 to 4, 0.46 mg QD on Days 5 to 7, and 0.92 mg QD on Day 8 in subjects with mild hepatic impairment

Drug: Ozanimod

Ozanimod in subjects with moderate hepatic impairment

EXPERIMENTAL

Participants will receive ozanimod 0.23 mg once daily (QD) on Days 1 to 4, 0.46 mg QD on Days 5 to 7, and 0.92 mg QD on Day 8 in subjects with moderate hepatic impairment

Drug: Ozanimod

Ozanimod in healthy subjects

EXPERIMENTAL

Participants will receive ozanimod 0.23 mg once daily (QD) on Days 1 to 4, 0.46 mg QD on Days 5 to 7, and 0.92 mg QD on Day 8 in healthy subjects

Drug: Ozanimod

Interventions

Ozanimod DRUG

Ozanimod

Also known as: RPC-1063, Zeposia

Ozanimod in healthy subjects; Ozanimod in subjects with mild hepatic impairment; Ozanimod in subjects with moderate hepatic impairment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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, or implantable
• Placement of an intrauterine device or intrauterine hormone-releasing system
• Bilateral tubal occlusion
• Vasectomized partner
• Complete sexual abstinence
• All participants:
• Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
• Each participant with mild or moderate hepatic impairment must satisfy the following criteria to be enrolled in the study:
• Participant has mild (5 to 6 points) or moderate (7 to 9 points) hepatic impairment per the Child-Pugh system (Appendix B).
• Participant should be enrolled into the group corresponding to the Child-Pugh classification score that most accurately reflects the most severe hepatic disease classification within the past 6 months of signing the ICF (based on past medical history or PE observation).
• If a Child-Pugh score was previously calculated and documented in the last 6 months, and it is more severe than the one calculated at Screening, then that previous value will be used for study entry purposes. If the Screening Child-Pugh score is more severe, then it will be used. If no score was calculated in the 6 months prior to Screening, then the score obtained at Screening will be used. Adequate documentation should be provided to substantiate the Child-Pugh score assigned to each participant.
• Participant must be medically stable for at least 4 weeks before Screening with clinically acceptable medical history (eg, no worsening of clinical signs of hepatic impairment, or no worsening of total bilirubin or prothrombin time by more than 50%), PE, clinical laboratory tests, vital signs, and 12-lead ECGs consistent with the underlying stable hepatic impairment condition, as judged by the Investigator.
• Participant with laboratory parameters that are considered clinically significant beyond those consistent with their degree of hepatic impairment may be included if, in the opinion of the Investigator and Medical Monitor, these findings will not interfere with the study or introduce additional safety risk to the participant.

You may not qualify if:

• The presence of any of the following will exclude a participant from enrollment:
• Participant has any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
• Participant has any condition that confounds the ability to interpret data from the study.
• Participant has a seated blood pressure outside 90 to 155 mmHg systolic or 50 to 95 mmHg diastolic at Screening or Day -1.
• Participant has a seated pulse rate outside 55 to 90 beats per minute (bpm) at Screening or Day -1.
• Participant has a positive serum test for human immunodeficiency virus (HIV) at Screening or Day -1.
• Participant with any active infection including hepatitis.
• Participant has a positive alcohol urine or breath test at Screening or Day -1.
• Participant 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.
• Participant has consumed pomelo-variety citrus fruits or juice (including pomelo, grapefruit, Seville oranges) within 7 days prior to the first dose of IP or herbal supplements including St. John's wort within 28 days prior to the first dose of IP.
• Participant fails or is unwilling to abstain from strenuous physical activities for at least 24 hours prior to the first dose of IP.
• Participant has poor peripheral venous access.
• Participant has donated greater than 400 mL of blood within 60 days prior to Day 1.
• Participant has history of hypersensitivity or allergic reaction to S1P receptor modulators.
• Participant has used any of the following systemic medications:

Sponsors & Collaborators

• Celgene: lead

Study Sites (3)

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Orlando Clinical Research Center OCRC

Orlando, Florida, 32809, United States

Location

The Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Liver Diseases; Digestive System Diseases; Lymphoma, Follicular

Interventions

ozanimod

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 20, 2020
• Study Start: December 18, 2020
• Primary Completion: April 6, 2022
• Study Completion: April 6, 2022
• Last Updated: June 14, 2022

Record last verified: 2022-06

Locations

US (3)