Phase I--study with aprosulate, a new synthetic anticoagulant

Area of Science:

• Pharmacology
• Clinical Trials
• Hemostasis

Background:

• Anticoagulant therapy is crucial for managing thrombotic disorders.
• Development of novel anticoagulants with defined structures is ongoing.
• Aprosulate is a new chemically synthesized anticoagulant with a molecular weight of 2388.

Purpose of the Study:

• To evaluate the safety, pharmacokinetics, and anticoagulant activity of aprosulate in healthy human volunteers.
• To determine the dose-response relationship of aprosulate.
• To assess the impact of aprosulate on coagulation parameters and bleeding time.

Main Methods:

• First-in-human, placebo-controlled, dose-escalation study.
• Twelve healthy male volunteers received subcutaneous injections.
• Ascending doses of aprosulate (0.25-2.0 mg/kg) administered on alternate days.
• Assessment of anticoagulant parameters (aPTT, Heptest), bleeding time, pharmacokinetics, and safety for 48 hours post-injection.

Main Results:

• Aprosulate showed a dose-dependent increase in activated partial thromboplastin time (aPTT) and Heptest.
• Anticoagulant effects persisted for up to ten hours post-injection.
• A trend towards prolonged bleeding time was observed at higher doses.
• Aprosulate was generally well-tolerated, with transient, spontaneous normalization of elevated plasma transaminase levels in some subjects.

Conclusions:

• Aprosulate exhibits predictable dose-dependent anticoagulant activity in humans.
• The drug demonstrates a generally favorable safety profile in the studied dose range.
• Further investigation is warranted to explore the therapeutic potential of aprosulate.