Estradiol in micellar nanoparticles: the efficacy and safety of a novel transdermal drug-delivery technology in the management of moderate to severe vasomotor symptoms.

OBJECTIVE

To assess the efficacy and safety of topical micellar nanoparticle estradiol emulsion (MNPEE; Estrasorb; Novavax, Inc., Malvern, PA) in postmenopausal women with moderate to severe vasomotor symptoms.

DESIGN

A multicenter, randomized, double-blind, placebo-controlled study was conducted in 200 postmenopausal women with seven or more moderate to severe hot flushes per day. The study consisted of a 3-week screening period followed by a 1-week placebo emulsion run-in period and a 12-week active or placebo treatment period. Women were randomized (1:1) to receive MNPEE (3.45 g daily dose of emulsion containing 8.6 mg estradiol) or matching placebo emulsion. The primary efficacy variable was the change from baseline in the frequency of moderate and severe hot flushes at weeks 4 and 12. Adverse events were monitored throughout the trial.

RESULTS

Topical micellar nanoparticle estradiol emulsion was statistically significantly superior to placebo emulsion in reducing the mean frequency of moderate to severe vasomotor symptoms by week 3 (P = 0.003), with superiority to placebo maintained from weeks 4 to 12 (P < 0.001). At week 12 (peak benefit), MNPEE reduced mean daily frequency of hot flush count by 11.1 (P < 0.001 vs placebo). MNPEE significantly reduced mean symptom severity from weeks 4 to 12 (P < 0.001) compared with placebo. At endpoint, mean serum concentrations of estradiol and estrone were 63 and 89 pg/mL, respectively, in the MNPEE group. The mean endpoint ratio of estradiol to estrone in these patients was 0.774. MNPEE was safe and well tolerated.

CONCLUSION

Once-daily application of 3.45 g of micellar nanoparticle estradiol emulsion containing 8.6 mg of estradiol was safe and effective in providing significant relief of vasomotor symptom frequency and severity in postmenopausal women.