Determine PK Profiles of Ozanimod and Its' Major Metabolites in Healthy Subjects

This is a single-dose, single-center, open-label, randomized, parallel relative bioavailability study (4 treatments and 1 period) of 3 test products of a Transdermal Delivery System of Ozanimod (Corplex Ozanimod TDS) with the Reference Listed Drug (Zeposia Capsule 0.92 mg), recruiting around 24 healthy (male: female = 1:1) subjects under fasting conditions.

The following goals will be procured through this study:

• To determine the pharmacokinetic profiles of Ozanimod and its' major metabolites (CC112273 and CC1084037) from the Corplex Ozanimod TDS (OZ-TDS 1, OZ-TDS 2 and OZ-TDS 3 manufactured by Corium Innovations, Inc.) (Test Product 1, Test Product 2 and Test Product 3) and the comparator (Zeposia Capsule 0.92 mg manufactured by Bristol Myers Squibb) (Reference Product) in healthy subjects;
• To compare the relative bioavailability between the Corplex Ozanimod TDS and the oral capsules in healthy subjects;
• To compare three formulations of the Corplex Ozanimod TDS in healthy subjects;
• To determine the safety and tolerability of the Corplex Ozanimod TDS vs the oral capsules in healthy subjects.

Inclusion criteria

• Subject age between 18 to 55 years old.
• Subject body weight ≤ 120 kg, with a BMI within 18-30 kg/m2.
• Subject is able to complete the clinical study including the follow-up.
• Subject is capable of providing written informed consent.

Exclusion criteria

• Breastfeeding female.
• Pregnancy test positive female.
• At rest systolic blood pressure outside 90-140 mmHg or diastolic blood pressure outside 50-90 mmHg.
• At rest sinus bradycardia defined as symptomatic heart rate < 50 bpm, or asymptomatic heart rate < 45 bpm; and sinus tachycardia defined as heart rate > 100 bpm.
• Clinically significant ECG abnormalities or 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.
• QTc > 450 ms for male and > 460 ms for female.
• A history of allergies, or any significant adverse reactions, to any medications, unless the clinician considers that they are not clinically significant.
• Clinically significant medical history of eyes, ears, nose, throat, respiratory, cardiovascular, gastrointestinal, genitourinary, neurological, haematopoietic, lymphatic, endocrine, metabolic, dermatological, musculoskeletal, psychological, family history or surgical history.
• Family history of sudden cardiac death.
• Clinically significant physical examination finding.
• Clinically significant laboratory abnormalities.
• Haemoglobin < 12.0 g/dL for male and < 11.0 g/dL for female at screening.
• Total bilirubin > 1.25 x upper limit of normal (unless it is an isolated elevation where the direct bilirubin is ≤ 35% of total), ALT/AST > 1.5 x upper limit of normal, or CK > 2 x upper limit of normal.
• Hepatitis B, Hepatitis C or HIV positive.
• Urine DOA test positive.
• Breath alcohol test positive.
• Any use of tobacco product(s) 30 days prior to study recruitment.
• A history of drug or substance abuse, including alcohol (≥ 14 units per week) within 6 months before consent taking (1 unit of alcohol equals approximately ½ pint [285 mL] of beer, 1 glass [125 mL] of wine, or 1 shot [25 mL] of spirit).
• Unable to refrain from taking any medications (including herbal remedies) within 7 days before dosing, with the exception of birth control medications and other medications deemed acceptable by the Investigator.
• Clinically significant illness or injury or hospitalisation for any reason within 28 days before consent-taking.
• Unable to refrain or has participation in other clinical study involving a marketed or investigational drug within 28 days or 10 half-lives of the drug before dosing, whichever is longer.
• Unable to refrain or has donation of > 500 mL of plasma within 14 days before dosing; or donation or loss of whole blood (excluding the amount of blood collected during screening) before dosing as follows:

• 50-300 mL within 28 days,
• 301-500 mL within 42 days, or
• > 500 mL within 84 days.
• Any upper arm conditions that will disallow study drug administration or difficulty to swallow the study drug.
• Any other medical condition or reason that, in the opinion of the Investigator or Research Physician, makes the subject unsuitable to participate in the clinical study.
• Unable to refrain from taking any of the following systemic medications:

Strong inhibitors of CYP3A, and all inhibitors of CYP2C8 or BCRP, (i.e., cyclosporine eltrombopag, geftinib) within 7 days or 5 half-lives, whichever is longer, prior to dosing or Strong inducers of CYP3A, and all inducers of CYP2C8 within 14 days or 5 half-lives, whichever is longer, prior to dosing, or 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.

• Female of childbearing potential unable to refrain from having unprotected sexual intercourse with any non-sterile male partner within 14 days before dosing; acceptable methods of contraception include:

• double barrier (1 by each partner), and at least 1 of these barriers (condom, cervical cap, diaphragm or sponge) must contain spermicide,
• hormonal (oral, injectable, transdermal, intravaginal or implantable),
• intrauterine contraceptive system,
• surgical (vasectomy or tubal ligation), or
• sexual abstinence.