HORMONAL EFFECTS OF MPV-2213AD, A NEW SELECTIVE AROMATASE INHIBITOR, IN HEALTHY MALE-SUBJECTS - A PHASE-I STUDY

Aims A novel non-steroidal competitive inhibitor of the aromatase enzy me, MPV-2213ad, was entered into an open dose-escalation study. The ob jective of this study was to investigate the tolerability and efficien cy of this new compound with assessment of the hormonal effects after study drug administration. Methods MPV-2213ad was given to 39 healthy male volunteers. Single increasing oral doses of 0.003, 0.03, 0.3, 3, 9, 30 and 100 mg were given to three subjects at each dose level, afte r which ten subjects received the 300 mg dose and eight subjects the h ighest 600 mg dose of MPV-2213ad. Results Serum oestradiol levels were suppressed by 58-65% when MPV-2213ad was given at doses between 0.3 a nd 30 mg. A reduction in serum oestradiol levels by 83% from baseline was achieved with the 300 mg dose. No additional decrease was seen wit h the highest dose. The suppression lasted longer with higher doses of MPV-2213ad. After the 300 and 600 mg doses serum oestradiol returned to baseline within 4 days. Marked increases in serum concentrations of testosterone, androstenedione, 17-OH-progesterone LH and FSH were als o observed at doses between 100 and 600 mg of MPV-2213ad. The drug was well-tolerated and the adverse events were mild or moderate including hot flushes, mild vertigo, nausea, acne and gastrointestinal discomfo rt. Conclusions MPV-2213ad has a potent, dose-dependent inhibitory eff ect on serum oestradiol. It was selective for the aromatase enzyme wit h no signs of adreno-cortical suppression or haematological or biochem ical toxicity.