Safety and Efficacy of Low-dose Mesylate Salt of Paroxetine (LDMP) for the Treatment of Vasomotor Symptoms (VMS) Due to Menopause: Pooled Results From Two Randomized, Placebo-controlled Phase 3 Studies

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 498-531-Female Repro Endocrinology & Case Reports
Clinical
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-510
James A Simon*1, Andrew Kaunitz2, Sailaja Bhaskar3 and Joel Lippman3
1George Washington University School of Medicine, Washington, DC, 2University of Florida College of Medicine, Jacksonville, FL, 3Noven Pharmaceuticals, Inc., New York, NY
Introduction: VMS, including hot flashes and night sweats, affect up to 80% of women experiencing menopause. Some women are unable or unwilling to use hormone therapy; therefore, nonhormonal therapies are needed. Preliminary study results found that LDMP (7.5 mg once daily for 8 weeks) was safe and efficacious in treating VMS due to menopause.

Methods: Two multicenter, double-blind, randomized, placebo-controlled, Phase 3 studies (one of 12- and the other of 24-wks’ duration) were conducted in postmenopausal women ≥40 years old with moderate to severe VMS (>7-8 hot flashes/d; 50-60/wk). Patients were randomized 1:1 to LDMP 7.5 mg or placebo once daily. Primary endpoints were mean change in frequency and severity of moderate to severe VMS from baseline (BL) to Wk 4 and Wk 12. In the 24-wk study, persistence of treatment benefit was also determined (responders = patients with ≥50% reduction in VMS frequency from BL to Wk 24). Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, electrocardiograms, and clinical laboratory abnormalities.

Results: Pooled efficacy and safety populations comprised 1174 (LDMP: 585; placebo: 589) and 1175 (LDMP: 586; placebo: 589) patients, respectively. Compared with placebo, LDMP significantly reduced the frequency of VMS at Wk 4 (p<0.0001) and Wk 12 (p<0.0001) and the severity of VMS at Wk 4 (p=0.0006) and Wk 12 (p=0.0110). Reduction in mean weekly VMS frequency and severity from BL became significantly different beginning at Wks 1 and 2, respectively, and continued through Wk 12 (p<0.0001 and p≤0.04 at all time points, respectively). Significantly more patients treated with LDMP than placebo were responders at Wk 24 (47.5% vs 36.3%, respectively; p=0.0066). Overall, 295/586 (50.3%) patients in the LDMP group and 275/589 (46.7%) patients in the placebo group experienced ≥1 TEAE; most were mild or moderate in severity. TEAEs reported in ≥2% of LDMP-treated patients and with ≥2-fold higher frequency than in the placebo group were nausea (LDMP: 3.8%; placebo: 1.4%), fatigue (LDMP: 3.4%; placebo: 1.5%), and dizziness (LDMP: 2.0%; placebo: 0.8%). No clinically meaningful changes in laboratory values, vital signs, or electrocardiograms were observed in either treatment group.

Conclusion:  LDMP was safe, well tolerated, and efficacious in reducing the frequency and severity of VMS due to menopause. Treatment benefit began as early as Wk 1 for frequency and Wk 2 for severity and persisted through Wk 24.

Disclosure: JAS: Consultant, Abbott Laboratories, Consultant, Agile Therapeutics, Advisory Group Member, Amgen, Consultant, Ascend, Consultant, BioSante, Consultant, Depomed, Consultant, Lelo Inc., Consultant, MD Therapeutics, Advisory Group Member, Merck & Co., Advisory Group Member, Novo Nordisk, Consultant, Novogyne, Advisory Group Member, Pfizer, Inc., Consultant, Shionogi Inc., Consultant, Slate Pharmaceuticals, Consultant, Sprout Pharmaceuticals, Advisory Group Member, Teva, Consultant, Warner Chilcott, Advisory Group Member, Watson Pharmaceuticals, Research Funding, BioSante, Research Funding, EndoCeutics Inc., Research Funding, Novo Nordisk, Research Funding, Novogyne, Research Funding, Palatin Technologies, Research Funding, Teva, Research Funding, Warner Chilcott, Speaker Bureau Member, Amgen, Speaker Bureau Member, Merck & Co., Speaker Bureau Member, Novartis Pharmaceuticals, Speaker Bureau Member, Novo Nordisk, Speaker Bureau Member, Novogyne, Speaker Bureau Member, Teva, Speaker Bureau Member, Warner Chilcott, Chief Scientific Officer, Sprout Pharmaceuticals. AK: Research Funding, Noven Pharmaceuticals. SB: Employee, Noven Pharmaceuticals. JL: Employee, Noven Pharmaceutical.

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: This study was funded by Noven Pharmaceuticals, Inc.