Objective: The purpose of this study was to assess the 1-year maintenance of the efficacy of desvenlafaxine 100 mg/day (administered as desvenlafaxine succinate) established on week 12 in a 1-year, double-blind, randomized, placebo-controlled trial in postmenopausal women seeking treatment of bothersome vasomotor symptoms.
Methods: Primary efficacy endpoints were changes in hot flush (HF) frequency and severity on weeks 12, 26, and 52 in an efficacy substudy population (≥50 moderate and severe HFs per week at baseline). Secondary endpoints were Greene Climacteric Scale, Patient Global Impression Symptom Rating, and Patient Global Impression of Change scores (weeks 12, 26, and 52) for the main study efficacy population. Safety was assessed throughout the trial.
Results: The mean baseline HF frequency (efficacy substudy population, n = 365) was 12 moderate and severe HFs per day; the mean baseline severity score was 2.4. At 1 year, women treated with desvenlafaxine maintained the efficacy established on week 12. Desvenlafaxine reduced HF frequency by 7.47 moderate and severe HFs per day on week 12 (adjusted mean difference from placebo, −2.48; 95% CI, −3.47 to −1.50; P < 0.001) and by 7.70 moderate and severe HFs per day on month 12 (adjusted mean difference from placebo, −2.86; 95% CI, −4.14 to −1.57; P < 0.001). Desvenlafaxine reduced the mean severity score by 0.63 on week 12 (placebo, −0.30; P < 0.001) and by 0.75 on month 12 (placebo, −0.44; P = 0.003). Reductions in Greene Climacteric Scale total score (main study efficacy population, n = 1,950) were significantly greater for desvenlafaxine than for placebo on months 3, 6, and 12 (all P < 0.001). Treatment-emergent adverse event rates were 84% for desvenlafaxine and 79% for placebo (P = 0.006). Full safety results are reported separately.
Conclusions: The treatment efficacy of desvenlafaxine 100 mg/day achieved on week 12 in postmenopausal women with vasomotor symptoms is maintained for 1 year.
In this study, treatment efficacy achieved at week twelve with desvenlafaxine 100mg/d in postmenopausal women with vasomotor symptoms was maintained for one year.
From the 1University of Virginia Health System, Charlottesville, VA; 2Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA; and 3Pfizer Inc., Collegeville, PA.
Received May 31, 2012; revised and accepted August 15, 2012.
Trial registration: ClinicalTrials.gov (NCT00683800).
Disclaimer: In September 2011, Pfizer Inc. received a Complete Response Letter from the US Food and Drug Administration on its application for approval to market desvenlafaxine for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. The Complete Response Letter states that the data included in the application are not sufficient to establish an acceptable risk-benefit profile for the treatment of VMS in the general population of postmenopausal women and that, therefore, desvenlafaxine is not approved for the treatment of VMS in the United States at this time. This decision does not impact the approval of desvenlafaxine for the treatment of major depressive disorder in adults.
Funding/support: This study was sponsored by Wyeth Research, which was acquired by Pfizer Inc. in October 2009. Pfizer Inc. funded medical writing support and medical editing support, which were provided by Kathleen Dorries, PhD, and Lorraine Sweeney, BA, respectively, both formerly at Embryon (a division of Advanced Health Media LLC) and currently at Peloton Advantage LLC.
Financial disclosure/conflicts of interest: In the past 12 months, J.V.P. has served as consultant (fees to the University of Virginia) to Pfizer Inc., Noven Pharmaceuticals, and Novogyne Pharmaceuticals; received grants/research support (fees to the University of Virginia) from DepoMed, Bionova, and Endoceutics; and received travel funds from Pfizer Inc., Noven Pharmaceuticals, and Novogyne Pharmaceuticals.
Address correspondence to: JoAnn V. Pinkerton, MD, Women’s Midlife Health Center, University of Virginia Health System, 2955 Ivy Road, Suite 104, Charlottesville, VA 22903. E-mail: JVP9U@Virginia.edu