Esmirtazapine treatment of postmenopausal vasomotor symptoms: two randomized controlled trials.

OBJECTIVES

Two identical 12-week, randomized, double-blind, placebo-controlled, multi-arm, parallel-group Phase III studies (Study P012, NCT00560833; Study P013, NCT00535288) evaluated the efficacy and safety of esmirtazapine, an investigational medicine, for the treatment of moderate to severe vasomotor symptoms (VMS) in postmenopausal women.

METHODS

Participants were randomized to placebo or esmirtazapine (2.25, 4.5, 9.0, or 18.0 mg). Co-primary efficacy endpoints (daily frequency and severity of moderate to severe VMS, both at weeks 4 and 12) were based on participative LogPad daily diaries. Adverse events (AEs) were recorded.

RESULTS

In Studies P012 and P013, 942 and 946 participants were randomized, respectively. Compared with placebo, esmirtazapine significantly reduced the mean daily frequency by 1.4-2.2 moderate to severe VMS at weeks 4 and 12 (both ≥4.5 mg) and mean daily severity by 0.06-0.08 symptoms at weeks 4 (≥4.5 mg) and 12 (9.0 mg P012; 18.0 mg P013 only). Esmirtazapine was generally well tolerated with a more favorable safety profile at lower doses. Somnolence and fatigue were the most frequently reported AEs.

CONCLUSIONS

Esmirtazapine reduced the frequency and severity of moderate to severe VMS associated with menopause and was generally well tolerated in the study population.