Study to Investigate the Absolute Bioavailability of a Single Oral Dose of Ponesimod in Healthy Male Subjects

Inclusion criteria

• Signed informed consent in the local language prior to any study-mandated procedure.
• Body mass index ≥ 18 and ≤ 28 kg/m^2 at screening.
• No clinically significant findings on the physical examination at screening.
• Systolic blood pressure (SBP) 100-145 mmHg and diastolic blood pressure (DBP) 50-90 mmHg, measured on the dominant arm, after 5 min in the supine position at screening and Day -1 of pilot phase/ first treatment period in main phase.
• 12-lead ECG without clinically relevant abnormalities at screening and Day -1 pilot phase / first treatment period in main phase.
• Negative results from urine drug screen at screening and Day -1 pilot phase / first treatment period in main phase.
• Hematology and clinical chemistry variables not deviating from the normal range to a clinically relevant extent at screening.
• Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study.

Exclusion criteria

• Known allergic reactions or hypersensitivity to the active compound or any excipients of the drug formulation(s).
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism, or excretion of the study drug (appendectomy and herniotomy allowed, cholecystectomy not allowed).
• Veins unsuitable for i.v. puncture on either arm (e.g., veins that are difficult to locate, access, or puncture or veins with a tendency to rupture during or after puncture).
• Heart rate < 50 or > 95 beats per minute (bpm) at screening or Day -1 of pilot phase / first treatment period in main phase on 12-lead ECG measured after 5 min in the supine position.
• PR interval (time interval from the beginning of the P wave to the beginning of the QRS complex) > 200 ms at screening and Day -1 of pilot phase / first treatment period in main phase.
• Subjects with personal or family history of long QT (time interval from beginning of the Q wave until end of the T wave) syndrome or hypokalemia.
• Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
• Previous exposure to the study medication within 3 months prior to screening.
• Any immunosuppressive treatment within 6 weeks or 5 half-lives of the drug, whichever is longer, before study drug administration.
• Treatment with another investigational drug within 3 months or 10 half-lives of the drug, whichever is longer, prior to screening or participation in more than 4 investigational drug studies within 1 year prior to screening.
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
• Excessive caffeine consumption, defined as ≥ 800 mg (7 cups of coffee or 14 cups of tea) per day at screening.
• Smoking within the last 3 months prior to screening and inability to refrain from smoking during the course of the study.
• Treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines) within 2 weeks prior to screening.
• Loss of 250 mL or more of blood within 3 months prior to screening.
• Lymphopenia (< 1000 cells/μL) at screening or Day -1 of pilot phase / first treatment period in main phase.
• Viral, fungal (with exception of onychomycosis and dermatomycosis), bacterial, or protozoal infection within 4 weeks before the first study drug administration.
• Positive results from the hepatitis serology, except for vaccinated subjects or subjects with past but resolved hepatitis, at screening.
• Positive results from the human immunodeficiency virus (HIV) serology at screening.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
• Legal incapacity or limited legal capacity at screening.