Inclusion criteria :|
- Healthy male or female subjects, between 18 and 55 years of age, inclusive.
- Body weight between 50.0 and 100.0 kg, inclusive, if male, and between 40.0 and 90.0
kg, inclusive, if female, body mass index between 18.0 and 32.0 kg/mÂ², inclusive.
- Certified as healthy by a comprehensive clinical assessment (detailed medical history
and complete physical examination).
- Normal vital signs after 10 minutes resting in supine position:
- 100 mmHg - 60 mmHg - 50 bpm - Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine
position in the following ranges; 120 ms - Laboratory parameters within the normal range, unless the Investigator considers an
abnormality to be clinically irrelevant for healthy subjects; however serum
creatinine, alkaline phosphatase, hepatic enzymes (aspartate aminotransferase, alanine
aminotransferase) should be strictly below the ULN. Total bilirubin out of normal
range can be acceptable if total bilirubin should not exceed 1.5 the upper limit with
normal conjugated bilirubin values (unless the subject has documented Gilbert
- Female subject must use a double contraception method including a highly effective
method of birth control except if she has undergone sterilization at least 3 months
earlier or is postmenopausal. The accepted double contraception methods include the
use of 1 of the following contraceptive options: (1) intrauterine device; (2) condom
or diaphragm or cervical/vault cap, in addition to spermicide. Menopause is defined as
being amenorrheic for at least 2 years with plasma follicle stimulating hormone (FSH)
value being within the normal range for postmenopausal women according to the local
laboratory. Hormonal contraception is NOT acceptable in this study due to drug
- Having given written informed consent prior to undertaking any study-related
- Any history or presence of clinically relevant cardiovascular, pulmonary,
gastrointestinal, hepatic, renal, metabolic, hematological, neurological,
osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or
signs of acute illness.
- History of renal disease, or significant abnormal kidney function test with glomerular
filtration rate (GFR) <90 mL/min as calculated using the Cockcroft-Gault equation.
- Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice
- Blood donation, any volume, within 2 months before inclusion.
- Symptomatic postural hypotension, irrespective of the decrease in blood pressure, or
asymptomatic postural hypotension defined as a decrease in systolic blood pressure â‰¥20
mmHg within 3 minutes when changing from supine to standing position.
- Presence or history of drug hypersensitivity, or allergic disease diagnosed and
treated by a physician.
- History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per
day on a regular basis).
- Smoking more than 5 cigarettes or equivalent per day, unable to stop smoking during
- Excessive consumption of beverages containing xanthine bases (more than 4 cups or
glasses per day)
- If female, pregnancy (defined as positive Î²-HCG blood test if applicable),
- Any medication (including St John's Wort) within 14 days before inclusion or within 5
times the elimination half-life or pharmacodynamic half-life of the medication; any
vaccination within the last 28 days and any biologics (antibody or its derivatives)
given within 4 months before inclusion. Any oral contraceptives during the screening
period or for at least 15 days prior to inclusion; any injectable contraceptives or
hormonal intrauterine devices within 12 months prior to inclusion; or topical
controlled delivery contraceptives (patch) for 3 months prior to inclusion.
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.