| Eligibility |
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 30.0 kg/m2, 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 and after 3 minutes in
standing position:
- 95 mmHg < systolic blood pressure (SBP) <140 mmHg
- 45 mmHg < diastolic blood pressure (DBP) <90 mmHg
- 40 bpm < heart rate (HR) <100 bpm
- Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine
position in the following ranges; 120 ms<PR<220 ms, QRS<120 ms, QTc=430 ms if male,
=450 ms if female and normal ECG tracing unless the Investigator considers an ECG
tracing abnormality to be not clinically relevant.
- 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), and total bilirubin (unless the subject has documented Gilbert
syndrome) should not exceed the upper laboratory norm.
- 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 2 of the following 3 contraceptive options: (1) intrauterine device; (2)
hormonal contraception; (3) condom or diaphragm or cervical/vault cap, in addition to
spermicide. Menopause is defined as being amenorrheic for at least 2 years with plasma
follicule-stimulating hormone (FSH) level >30 UI/L. Hormonal contraception is
acceptable in this study (contraceptive guidance will be described in the study
protocol).
- Having given written informed consent prior to undertaking any study-related
procedure.
- Not under any administrative or legal supervision.
- Male subject, whose partners are of childbearing potential (including lactating
women), must accept to use, during sexual intercourse, a double contraception method
according to the following algorithm: (condom) plus (intra-uterine device or hormonal
contraceptive) from the inclusion up to 3 months after the last dosing. Male subject,
whose partners are pregnant, must use, during sexual intercourse, a condom from the
inclusion up to 3 months after the last dosing.
- Male subject has agreed not to donate sperm from the inclusion up to 3 months after
the last dosing.
Exclusion criteria:
- Any history or presence of clinically relevant cardiovascular, pulmonary,
gastrointestinal (especially pancreatitis), hepatic (especially biliary disease,
including cholecystectomy), renal, metabolic, hematological, neurological,
musculoskeletal, articular, psychiatric, systemic, ocular, gynecologic (if female), or
infectious disease, or signs of acute illness.
- History of renal disease, or significantly abnormal kidney function test (glomerular
filtration rate (GFR) <90 mL/min as calculated using the Cockcroft-Gault equation (7)
at screening.
- Frequent headaches and/or migraine, recurrent nausea and/or vomiting (more than twice
a month).
- Blood donation of a pint or more 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 =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 and/or unable to stop smoking
during the study.
- Excessive consumption of beverages containing xanthine bases (more than 4 cups or
glasses per day).
- If female, pregnancy (defined as positive human chorionic gonadotropin (ß-HCG blood
test), breast-feeding.
- Any medication (over-the counter or prescription medications, including St John's
Wort), or any herbal supplements or supra-therapeutic vitamins within 14 days before
inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of
the substance; any vaccination within the last 28 days, and any biologics (antibody or
its derivatives) given within 4 months before inclusion.
- Any subject who, in the judgment of the Investigator, is likely to be noncompliant
during the study, or unable to cooperate because of a language problem or poor mental
development.
- Any subject in the exclusion period of a previous study according to applicable
regulations.
- Any subject who cannot be contacted in case of emergency.
- Any subject who is the Investigator or any sub-investigator, research assistant,
pharmacist, study coordinator, or other staff thereof, directly involved in conducting
the study.
- Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen,
anti hepatitis C virus antibodies, anti-human immunodeficiency virus 1 and 2
antibodies (anti HIV1 and anti HIV2 Ab).
- Positive result on urine drug screen (amphetamines/methamphetamines, barbiturates,
benzodiazepines, cannabinoids, cocaine, opiates).
- Positive alcohol test.
- Any consumption of citrus (grapefruit, orange, etc) or their juices within 5 days
before inclusion.
- Any history or presence of deep leg vein thrombosis or pulmonary embolism or a
recurrent or frequent history of deep vein thrombosis in first degree relatives
(parents, siblings or children).
- Any presence or history of urinary tract infection or genital mycotic infection in the
last 4 weeks before screening.
The above information is not intended to contain all considerations relevant to a patient's
potential participation in a clinical trial.
|
