Pharmacokinetics Study: Determination of Naproxcinod and Its Metabolites After Oral Administration in Male

Inclusion criteria

1.

• Healthy, non smoker male subjects aged 18 to 45 years (inclusive).
• Body Mass Index (BMI) between 18 and 30 kg/m² (inclusive) with body weight (BW) ≥ 50 kg.
• Normal physical examination (non clinically significant abnormalities), as judged by the investigator.
• Normal electrocardiogram (ECG) (12-lead), (non clinically significant abnormalities), as judged by the Investigator.
• Supine Systolic Blood Pressure (SBP) between 100 and 139 mmHg (inclusive) and Diastolic Blood Pressure (DBP) between 50 and 89 mmHg (inclusive) (mean of 3 measurements).
• Supine Heart Rate (HR) between 45 and 90 bpm (inclusive).
• Oral body temperature (BT) between 36 and 37.5°C (inclusive).
• Subject must be able to understand the written information sheet and informed consent and comply with all study requirements.
• Subject must provide a written, dated and signed informed consent prior to any study procedure.

Exclusion criteria

• History of hypersensitivity reactions (such as asthma, rhinitis, or urticaria) to aspirin, naproxen or any other non steroidal anti-inflammatory drugs (NSAIDs); or hypersensitivity or contraindications to organic nitrate drugs; or to L-proline.
• History of any clinically relevant gastrointestinal (such as gastritis or gastric ulcer), respiratory, psychiatric, neurologic, kidney, liver, cardiac disease, bleeding disorder, other disease/condition or abnormal physical finding which may interfere with the study objectives, as judged by the Investigator.
• After 1 minute in a standing position, a drop of more than 20 mmHg in SBP or 10 mmHg in DBP compared to supine position (mean of 3 measurements) and a clinical manifestation of postural hypotension.
• Any clinically significant abnormal laboratory values, including creatinine clearance ≤ 80 mL/min as calculated with the Cockcroft-Gault formula.
• Seropositivity for HBs Ag, HCV Ab, HIV 1 or HIV 2 Ab.
• Any history of alcohol or drug abuse, or addiction within the last 2 years prior to enrollment.
• Positive drug screening (opiates, cannabinoids, cocaine, methadone, amphetamines, barbiturates, ecstasy).
• Positive alcohol or cotinine test.
• Donation of blood, plasma or platelets within 3 months prior to the Screening visit or donation planned during the 3 months following the study.
• Regular consumption of grapefruit juice or beverages containing xanthine bases (coffee, tea, cola: more than 5 cups or glasses a day).
• Current smokers or smoking history < 6 months.
• Current participation or participation within 3 months prior to the Screening visit, in another investigational drug or device study, or previous enrolment in the present study.
• Chronic use of any drugs (prescription or over the counter [OTC]) within 4 weeks prior to enrollment (single use of medication such as paracetamol for headache is allowed, except during the week before enrollment).
• Use of antioxidant vitamin supplements within 1 week prior to enrollment.
• Use of mouthwash or toothpaste containing chlorhexidine within 1 week prior to randomization (applicable only for study Part 1).
• In custody due to an administrative or a legal decision, or under tutelage, or being admitted to a sanitary or social institution.
• Any direct or indirect involvement with the study conduct or staff at site or any family link with study site staff.