Safety of AT-1015, a novel 5-HT2A antagonist, in combination with high-dose aspirin: an open-label study.

Objective: To assess the safety of AT-1015 in combination with high-dose aspirin (300 mg daily). Study subjects were 17 healthy male volunteers.

Methods: This was an open-label, single-center study. Subjects received aspirin 300 mg once daily, alone on days 1-4, and together with AT-1015 40 mg twice daily on days 5-11. A follow-up assessment was performed on day 18. The primary outcome measure was bleeding time; secondary outcome measures were vital signs, adverse events, physical examinations, 12-lead electrocardiograms (ECG) and laboratory safety tests.

Results: There was a significant increase in bleeding time between screening and the end of the aspirin-only period (mean bleeding time 4.8 vs 7.6 min, p = 0.01), but there were no further significant increases during the combination treatment period. The most common adverse events were dry mouth, epistaxis, gingival bleeding and abdominal pain. All treatment-related adverse events were mild in severity and no major bleeding episodes occurred. There were no clinically significant changes in vital signs, physical examinations, 12-lead ECGs or laboratory safety tests.

Conclusions: AT-1015 was safe and well-tolerated in healthy male volunteers when taken in combination with high-dose aspirin, and did not significantly prolong bleeding time compared with aspirin alone.