A Phase 1, Multicenter, Open-Label Study to Evaluate the Effect of Mild or Moderate Hepatic Impairment on the Multiple-Dose Pharmacokinetics of Ozanimod
Overview
- Phase
- Phase 1
- Intervention
- Ozanimod
- Conditions
- Liver Diseases
- Sponsor
- Celgene
- Enrollment
- 26
- Locations
- 3
- Primary Endpoint
- Pharmacokinetics - Cmax on Day 8 (Ozanimod, CC112273 and CC1084037)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Inclusion Criteria for Participants with Mild or Moderate Hepatic Impairment (Groups 1 and 2)
Exclusion Criteria
- •Exclusion Criteria for All Participants
- •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 -
- •Participant has a seated pulse rate outside 55 to 90 beats per minute (bpm) at Screening or Day -
- •Participant has a positive serum test for human immunodeficiency virus (HIV) at Screening or Day -
- •Participant with any active infection including hepatitis.
- •Participant has a positive alcohol urine or breath test at Screening or Day -
- •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.
Arms & Interventions
Ozanimod in subjects with mild hepatic impairment
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
Intervention: Ozanimod
Ozanimod in subjects with moderate hepatic impairment
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
Intervention: Ozanimod
Ozanimod in healthy subjects
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
Intervention: Ozanimod
Outcomes
Primary Outcomes
Pharmacokinetics - Cmax on Day 8 (Ozanimod, CC112273 and CC1084037)
Time Frame: Up to day 8
Maximum observed plasma concentration
Pharmacokinetics - AUClast on Day 8 (Ozanimod, CC112273 and CC1084037)
Time Frame: Up to day 8
AUC from time zero to the last measured time point
Pharmacokinetics - AUC∞ on Day 8 (Ozanimod, CC112273 and CC1084037)
Time Frame: Up to day 8
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Pharmacokinetics - Cmin on Day 8 (Ozanimod, CC112273 and CC1084037)
Time Frame: Up to day 8
Minimum observed plasma concentration
Pharmacokinetics - AUCtau on Day 8 (Ozanimod, CC112273 and CC1084037)
Time Frame: Up to day 8
Area under the plasma concentration-time curve from time zero to dosing interval
Secondary Outcomes
- Adverse Events (AEs)(From the time the ICF is signed until 64 ± 3 days after the last dose of ozanimod treatment)
- Pharmacokinetics - Vz/F (Ozanimod)(From Day 8 till Day 72)
- Pharmacokinetics - AUClast (Ozanimod, CC112273 and CC1084037)(From Day 8 till Day 72)
- Pharmacokinetics - AUCtau,u (Ozanimod, CC112273 and CC1084037)(Days 1, 5, and 8)
- Pharmacokinetics - AUC∞,u (Ozanimod, CC112273 and CC1084037)(From Day 8 till Day 72)
- Pharmacokinetics - AUClast,u (Ozanimod, CC112273 and CC1084037)(From Day 8 till Day 72)
- Pharmacokinetics -Cmin on Days 1 and 5 (Ozanimod, CC112273 and CC1084037)(Days 1, and 5)
- Pharmacokinetics - Tmax (Ozanimod, CC112273 and CC1084037)(Days 1, 5, and 8)
- Pharmacokinetics - Cmax,u (Ozanimod, CC112273 and CC1084037)(Days 1, 5, and 8)
- Pharmacokinetics -Cmax on Days 1 and 5 (Ozanimod, CC112273 and CC1084037)(Days 1 and 5)
- Pharmacokinetics - fu (Ozanimod, CC112273 and CC1084037)(Day 1 and Day 8)
- Pharmacokinetics - M/P AUCtau ratio (CC112273 and CC1084037)(Days 1, 5, and 8)
- Pharmacokinetics - AUCtau on Days 1 and 5 (Ozanimod, CC112273 and CC1084037)(Days 1 and 5)
- Pharmacokinetics - t1/2 (Ozanimod, CC112273 and CC1084037)(From Day 8 till Day 72)
- Pharmacokinetics - CL/F (Ozanimod)(From Day 8 till Day 72)