| Eligibility |
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)
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.
- Participant must be stable on a concomitant medication and/or treatment regimen
(defined as not starting a new treatment/medication[s] or a change in the dosage or
frequency of the concomitant medication[s] within 2 weeks before dosing with
ozanimod).
- Participant must have estimated creatinine clearance = 50 mL/min at Screening as
calculated by the Cockcroft-Gault formula.
Inclusion Criteria for Matched Normal Hepatic Function Participants (Group 3)
Each matched participant must satisfy the following criteria to be enrolled in the study:
- Participant is in good health as determined by past medical history, PE, vital signs,
ECG, and clinical laboratory safety tests. Clinical laboratory safety tests (ie,
hematology, coagulation, chemistry, and urinalysis) must be within normal limits or
clinically acceptable as judged by the Investigator.
- Participant must match a participant in Groups 1 and/or 2, with respect to sex, age (±
10 years), weight (± 20%) and smoking status. One normal hepatic function participant
can be matched to 2 hepatic impairment participants (one in Group 1 and one in Group
2), but no more than one hepatic impairment participant in the same group.
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 -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:
1. Strong inhibitors of CYP3A, and all inhibitors of CYP2C8 or BCRP, (ie,
cyclosporine, eltrombopag, gefitinib) within 7 days or 5 half-lives, whichever is
longer, prior to Day 1, or
2. Strong inducers of CYP3A, and all inducers of CYP2C8 within 14 days or 5
halflives, whichever is longer, prior to Day 1, or
3. Any known MAO inhibitors within 30 days or 5 half-lives, whichever is longer,
prior to Day 1. Examples of MAO inhibitors include but are not limited to
phenelzine, selegiline, isocarboxazid, rasagiline, tranylcypromine, pargyline,
procarbazine, and furazolidone.
- Participant who in the last 6 months of signing the ICF experienced myocardial
infarction, unstable angina, stroke, transient ischaemic attack, decompensated heart
failure requiringmhospitalization or New York Heart Association (NYHA) Class III/IV
heart failure.
- Participant with history or presence of second-degree atrioventricular (AV) block Type
II or third-degree AV block or sick sinus syndrome unless the patient has a
functioning pacemaker.
- Participant with history of cardiac arrest, cerebrovascular disease, uncontrolled
hypertension, or severe untreated sleep apnoea, history of recurrent syncope or
symptomatic bradycardia
- Participant with pre-existing significant QT interval prolongation (QTc greater than
500 msec) or other risks for QT prolongation, and patients on medicinal products other
than beta-blockers and calcium-channel blockers that may potentiate bradycardia.
- Participant on class Ia (eg, quinidine, disopyramide) or class III (eg, amiodarone,
sotalol) antiarrhythmic medicinal products, which have been associated with cases of
torsades de pointes in patients with bradycardia have not been studied with ozanimod.
Exclusion Criteria for Participants with Hepatic Impairment (Groups 1 and 2)
The presence of any of the following will exclude a hepatically-impaired participant from
enrollment:
- Participant has any serious medical condition (excluding hepatic impairment and
related complications), clinically significant laboratory abnormality not related to
hepatic impairment and related complications, or psychiatric illness that would
prevent the participant from participating in the study per Investigator discretion.
- Participant has current hepatic encephalopathy with time-or place-disorientation,
somnolence, stupor, coma, no personality/behavior, rigidity, or hyperactive reflexes -
or has had such within 1 month of Screening.
- Participant has planned liver transplantation within 6 months of Screening or has
received a liver transplant, transjugular intrahepatic portosystemic shunt, or
transjugular intrahepatic portosystemic stent shunting procedure.
- Participant has a history of alcoholism, drug abuse, or addiction within 6 months
prior to Screening.
- Participant has a positive urine drug screen including cotinine (non-smokers and
former smokers only) (except for prescribed medications such as benzodiazepines) at
Screening or Day -1. Tetrahydrocannabinol use (as permitted by local law) is not
allowed within 14 days prior to Day 1 and during the study.
- Participant has any history of cholecystectomy, clinically significant cardiovascular
or cerebrovascular disease.
- Participant has severe ascites at Screening or Day -1.
- Participant has hepatocellular carcinoma or acute liver disease (eg, caused by an
infection or drug toxicity).
- Participant chronically or routinely uses more than 2 g of acetaminophen daily.
Exclusion Criteria for Matched Normal Hepatic Function Participants (Group 3)
The presence of any of the following will exclude a matched normal hepatic function
participant from enrollment:
- Participant has any significant medical condition or psychiatric illness that would
prevent the participant from participating in the study (as determined by the
Investigator).
- Participant has a history of alcoholism, drug abuse, or addition within 24 months
prior to Screening.
- Participant has a positive test result for hepatitis B surface antigen and/or
hepatitis C antibody.
- Participant has a positive urine drug test (except for cotinine in smokers) at
Screening or Day -1.
- Participant has used any systemic over-the-counter medication (excluding acetaminophen
up to 2 g/day and low dose aspirin) within 7 days prior to Day 1, or any systemic
prescription medication (except for contraceptives) within 28 days or 5-half-lives,
whichever is longer, prior to Day 1.
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