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 enzyme, MPV-2213ad, was entered into an open dose-escalation study. The objective of this study was to investigate the tolerability and efficiency 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, after which ten subjects received the 300 mg dose and eight subjects the highest 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 and 30 mg. A reduction in serum oestradiol levels by 83% from baseline was achieved with the 300 mg dose. No additional decrease was seen with 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 also 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 discomfort. Conclusions MPV-2213ad has a potent, dose-dependent inhibitory effect on serum oestradiol. It was selective for the aromatase enzyme with no signs of adreno-cortical suppression or haematological or biochemical toxicity.