PII‐34

PURPOSE To evaluate safety and tolerability of PRX‐00023 following multiple oral doses of PRX‐00023 in healthy subjects. METHODS 32 healthy subjects were administered placebo or PRX‐00023 (10 to 60 mg) QD in a 28 day ascending dose study and 16 healthy subjects were dose titrated up to 150 mg QD in an open‐label multiple dose study. As a part of the drug development program, PK and 12‐lead ECG data were routinely collected in all subjects throughout the dose titration portion of the study. In addition, other safety parameters were measured and AEs were monitored throughout the study. RESULTS The most common AEs were headache and lightheadedness and there were no SAEs. Plot of PRX‐00023 serum concentration versus change from baseline in the QTcF interval length (Delta QTcF) suggest lack of effect with increase in serum concentration (highest C max observed was 649 ng/mL). In the 28‐day multiple dose study, the number of subjects with ≥ 30 msec to < 60 msec increase observed in the placebo group were comparable to those in the PRX‐00023 treatment groups. Moreover, in all the clinical studies, no subjects had ≥ 60 msec increase in change from baseline in the QTcF interval length. There were no clinically significant changes in vital signs in this study. CONCLUSIONS PRX‐00023 was well tolerated. The serum concentration‐delta QTcF relationship showed lack of ECG changes with increase in PRX‐00023 exposure. There were minimal adverse effects at any dose, consistent with expectation of a selective 5HT1A agonist. Clinical Pharmacology & Therapeutics (2005) 79 , P45–P45; doi: 10.1016/j.clpt.2005.12.159