Phase III studies show LDMP to be safe and effective for treatment of vasomotor symptoms in menopausal women.
Pooled results of recent phase III clinical studies indicate that low-dose mesylate salt of paroxetine (LDMP) is both well-tolerated and effective for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause.
James A. Simon, MD, clinical professor of Obstetrics and Gynecology at the George Washington University School of Medicine in Washington, DC, and colleagues reported their findings at ENDO 2013: The Endocrine Society’s 95th Annual Meeting and Expo in San Francisco on June 15, 2013.
According to the researchers, up to 80% of menopausal women in the United States are affected by vasomotor symptoms, such as hot flashes and night sweats, and hormone therapy is currently the only FDA-approved treatment. However, they opine, alternative treatments are needed because many of these patients cannot or choose not to take hormone therapy.
Previous studies have shown LDMP to be efficacious and well-tolerated for the treatment of moderate to severe menopausal VMS. The current study was designed to further evaluate the safety and efficacy of LDMP, as compared with placebo, by pooling the results of two multicenter, randomized, placebo-controlled Phase III studies.
After a 12-day run-in period, postmenopausal women who reported at least 7-8 moderate to severe hot flashes per day (or 50-60 per week) were randomly assigned 1:1 to receive LDMP 7.5 mg or placebo daily. Primary endpoints included the mean changes in frequency and severity of hot flashes from baseline to week 4 and also from baseline to week 12. Secondary endpoints included safety and persistence of treatment benefit.
LDMP was associated with significant reductions in the frequency of VMS both at 4 weeks (p < 0.0001) and at 12 weeks (p < 0.0001) compared with placebo. A significant difference was noted as early as week 1. LDMP also reduced the severity of VMS at week 4 (p = 0.0006) and week 12 (p = 0.0110) when compared with placebo, with a significant difference beginning at week 2. At week 24, 47.5% of patients treated with LDMP were responders, compared to 36.3% of the patients treated with placebo (p = 0.0066).
Most treatment-emergent adverse effects (TEAEs) were considered mild or moderate in severity and were experienced by 50.3% of patients receiving LDMP and 46.7% of patients receiving placebo. The rate of discontinuation for the LDMP treatment group was 4.4%, compared with 3.6% of the placebo group. Serious adverse events were reported by 2.4% and 1.4% of patients receiving LDMP and placebo, respectively. One death was reported in the treatment group; a 55 year old woman experienced fatal acute respiratory failure 68 days after starting treatment. This was deemed by the investigator to be unrelated to treatment.
Compared with placebo, LDMP significantly reduced the frequency and severity of VMS in postmenopausal women. With early treatment effect and low discontinuation rate, the authors conclude that “LDMP represents a potential nonhormonal treatment option for women with VMS who seek symptom relief.”