Safety, Pharmacokinetic and -Dynamic Study of PR-15, an Inhibitor of Platelet Adhesion

An Open-Label, Dose-Escalating Safety and Pharmacokinetic Study of an Acute Intravenous Administration of PR-15, an Inhibitor of Platelet Adhesion, in Six Different Strengths in Healthy Male Volunteers

Primary objective:

To evaluate safety and tolerability, adverse events (AEs), vital signs, ECG, bleeding time, evaluation of antibody titer and safety laboratory tests

Secondary objectives:

To evaluate the pharmacokinetics and pharmacodynamics (platelet aggregation)of six ascending single intravenous doses of PR-15 in healthy volunteers

Primary objective:

To evaluate safety and tolerability by using adverse events (AEs), vital signs including blood pressure/pulse rate (BP/PR), electrocardiographic examinations (12 lead ECG), bleeding time, evaluation of antibody titer and safety laboratory tests (biochemistry, hematology, coagulation, urinalysis)

Secondary objectives:

To evaluate the pharmacokinetics and pharmacodynamics (collagen-induced platelet aggregation)of six ascending single intravenous doses of PR-15 in healthy, male volunteers

Inclusion Criteria:

• Healthy, male Caucasians between 18 and 45 years of age.
• Normotensive subjects (systolic BP < 140 mmHg and diastolic BP <90 mmHg;
• Body weight of 70 to 90 kg (BMI 20 - 25.
• Negative results in HIV antibody, HBs antigen (HBsAg) and HCV tests;
• Signed Informed Consent Form.
• Normal coagulation function (aPTT between 24 and 35 seconds, PT between 70 and 130%, INR between 0.85 and 1.15.

Exclusion Criteria:

• Subjects who are taking or have taken any prescription medication within the last 14 days or any non-prescription medication, especially, anti-platelet drugs, within the last seven days prior to the administration of trial medication on Day 1.
• Intake of any investigational drug within three months prior to the administration of study medication on Day 1.
• Concomitant use of any other medication including over-the-counter preparations.
• History of hypersensitivity, contraindication or serious adverse reaction to inhibitors of platelet aggregation or hypersensitivity to related drugs (cross-allergy) or to any of the excipients in the study drug.
• A history or clinical evidence of any cardiac, cardio- or cerebrovascular, hepatic, renal, pulmonary, endocrine, neurological, infectious, gastrointestinal, haematological, oncological or psychiatric disease or emotional problems or any other clinically relevant condition, physical finding, ECG- or laboratory test abnormality, which - in the opinion of the investigator - would pose a significant risk for the subject, invalidate the Informed Consent or limit the ability of the subject to comply with study requirements or interfere otherwise with the conduct of the study.
• Any laboratory value outside the normal laboratory reference range at Screening and before randomization, unless approved by the investigator.
• Subjects known to have experienced elevated liver enzyme values will also be excluded.
• History of alcohol and/or drug abuse (verified by drug screening).
• Blood loss of 450 ml or more during the last three months before Screening.
• Subjects who smoke more than 5 cigarettes per day and/or are unable to abstain from smoking during the entire in-house period.
• Subjects who were previously enrolled in this trial or who have received PR-15 in a previous trial.
• Subjects who have participated in other clinical trials in the last 3 months.