Date: 2014-10-14
Type of information: Publication of results in a medical journal
phase: 3
Announcement: publication of results in Menopause
Company: Noven Pharmaceuticals (USA - FL)
Product: Brisdelle® (paroxetine)
Action mechanism:
Disease: moderate to severe hot flashes associated with menopause
Therapeutic area: Women health
Country:
Trial details:
Latest
news: * On October 14, 2014, Noven Pharmaceuticals announced the publication of data on the effects of low-dose mesylate salt of paroxetine (LDMP), marketed as Brisdelle® (paroxetine) capsules, 7.5 mg, in the October 2014 issue of Menopause, the peer-reviewed, scientific journal of The North American Menopause Society (NAMS). The article, “Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause,” presents exploratory analyses from pooled results that measured the impact of Brisdelle® on weight and sexual function within two, double-blind, randomized, placebo-controlled Phase 3 trials of women with moderate to severe vasomotor symptoms (VMS), commonly referred to as hot flashes. The article describes the exploratory analyses of pooled data from the two Phase 3 Brisdelle trials. The analyses showed that the frequency of treatment-emergent sexual dysfunction and weight change from baseline were similar between Brisdelle and placebo. As noted in the article, there are limitations to these analyses and it is unknown whether either might appear as an adverse event with longer term therapy. To view the full article published in Menopause please click here for article access. Brisdelle was specifically studied and FDA-approved to treat moderate to severe VMS associated with menopause. Brisdelle, at 7.5 mg, is a lower dose of paroxetine than that used to treat a number of psychiatric disorders. Brisdelle has not been studied in or approved for any psychiatric use. Data collected in the 12 week and 24 week Phase 3 studies and analyzed in the article included changes in body mass index (BMI) and weight, Arizona Sexual Experiences Scale (ASEX), Hot Flash-Related Daily Interference Scale (HFRDIS) sexuality subscore, and adverse events (AEs) related to weight or sexual dysfunction. The article includes results for each of these assessments at week 4, 12 (pooled data) and 24 (24-week study). Percentage change in median body weight from baseline to Week 4 was 0% in the Brisdelle arm and +0.21% in the placebo arm. The change from baseline in mean body weight at week 12 was +0.17% with Brisdelle and +0.52% with placebo and at week 24 was +0.48% with Brisdelle and +0.09% with placebo. Median change from baseline in BMI and proportion of subjects with weight gain of ≥7% compared to baseline were also analyzed, and the difference between Brisdelle and placebo trended similarly. As noted in the article, at the onset of these studies almost 60% of participants reported sexual dysfunction based on the ASEX. The proportion of participants reporting sexual dysfunction in the Brisdelle group compared to placebo at 4 weeks was 56% in both arms, 55% vs 52% at week 12, and 56% vs 57% at week 24, respectively. HFRDIS subscore results were also analyzed and the difference between Brisdelle and placebo trended similarly. Data regarding weight gain and sexual function (as measured by ASEX) were prospectively collected in both Phase 3 clinical trials. They were not, however, primary endpoints nor pre-specified in the statistical analysis plan and the article presents exploratory analyses of pooled data. The ASEX scale has only been validated in psychiatric patients taking antidepressants. HFRDIS was a pre-specified secondary endpoint in these studies, but the sexuality subscore was evaluated separately in the analyses in this article. The HFRDIS sexuality subscore is not validated for standalone use. The article notes other limitations of the study, including that the study was not specifically designed to evaluate sexual dysfunction in VMS and that the study had a relatively short 24-week duration of treatment and follow-up. The results of these analyses were also selected for oral presentation at the 2013 Annual Meeting of The North American Menopause Society and are publicly available on clinicaltrials.gov. The authors include: David J. Portman, M.D., Columbus Center for Women’s Health Research, Columbus, OH; Andrew M. Kaunitz, M.D., University of Florida College of Medicine, Jacksonville, FL; Kazem Kazempour, Ph.D. and Hana Mekonnen, M.A., Amarex Clinical Research, Germantown, M.D.; and Sailaja Bhaskar, Ph.D. and Joel Lippman, M.D., Noven Pharmaceuticals, Inc., New York, NY. Conflicts of interest and financial disclosures are presented below.
