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Phase 3 randomized controlled study of gastroretentive gabapentin for the treatment of moderate-to-severe hot flashes in menopause

Pinkerton, JoAnn V. MD1; Kagan, Risa MD2; Portman, David MD3; Sathyanarayana, Rekha BS4; Sweeney, Michael MD4for the Breeze 3 Investigators

doi: 10.1097/GME.0b013e3182a7c073
Original Articles
Editorial

Objective The goal of this study was to evaluate the efficacy and safety of gastroretentive gabapentin (G-GR) for the treatment of moderate-to-severe menopausal hot flashes.

Methods The primary endpoints of this randomized, placebo-controlled study of G-GR (600 mg am/1,200 mg pm) were the mean daily frequency and severity of hot flashes at weeks 4 and 12. Secondary endpoints included Patients’ Global Impression of Change, Clinicians’ Global Impression of Change, and daily sleep interference at week 24.

Results Six hundred women with 7 or more moderate-to-severe hot flashes/day enrolled; 66.2% completed 24 weeks of treatment. At weeks 4 and 12, G-GR–treated women experienced significantly greater reductions in mean hot flash frequency and severity than placebo-treated women (frequency: week 4, −1.7, P < 0.0001; week 12, −1.14, P = 0.0007; severity: week 4, −0.21, P < 0.0001; week 12, −0.19, P = 0.012). Similar reductions were maintained up to week 24. On the Patient Global Impression of Change, more women receiving G-GR than placebo were “much” or ”very much” improved (week 12: 58% vs 44%, P = 0.0008; week 24: 76% vs 55%, P < 0.0001). G-GR significantly reduced sleep interference compared with placebo at week 12 (P = 0.0056) and week 24 (P = 0.0084). Approximately 5% more women taking G-GR withdrew because of adverse events (G-GR/placebo, 16.7%/11.5%). The most common adverse events were dizziness (12.7%/3.4%), headache (9.3%/8.1%), and somnolence (6.0%/2.7%); incidences dropped to sustained low levels after a few weeks.

Conclusions G-GR is a modestly effective nonhormone therapy option for the treatment of moderate-to-severe hot flashes due to menopause and is well tolerated with titration.

From the 1Division of Midlife, Department of Obstetrics and Gynecology, University of Virginia Health Sciences Center, Charlottesville, VA; 2East Bay Physicians Medical Group, Sutter East Bay Medical Foundation, Berkeley, CA; 3Columbus Center for Women’s Health Research, Columbus, OH; and 4Depomed Inc, Newark, CA.

Received May 31, 2013; revised and accepted August 1, 2013.

Clinical trial registration: NCT01080300 (www.clinicaltrials.gov).

Funding/support: This study was funded by Depomed Inc.

Financial disclosure/conflicts of interest: J.V.P. has served as a consultant (fees to the University of Virginia) for Pfizer, Noven Pharmaceuticals, Depomed, and Shionogi; received grants/research support (fees to the University of Virginia) from Depomed, Bionova, and Endoceutics; and received travel funds from Pfizer, Noven Pharmaceuticals, Shionogi, and Depomed. R.K. has served as a consultant and advisory board member for Merck, Pfizer, Amgen, Noven, Novo Nordisk, Depomed, and Shionogi; has received research support and travel support from Depomed; has served on the speakers bureaus of Novo Nordisk, Noven, Novogyne, and Shionogi; is a member of the scientific advisory boards of the American Bone Health, The North American Menopause Society (through October 2012), and the American Orthopedics Association—Own the Bone; and has provided legal consulting for Merck and Warner Chilcott. D.P. has served as a consultant to Noven, Meda, and Teva; has received research grants from Noven, Depomed, Teva, Pfizer, and Bayer (paid to Columbus Center for Women’s Health Research); and has served on the speakers bureaus of Noven, Teva, and Warner Chilcott. M.S. and R.S. are employees of Depomed Inc and are shareholders in the company.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.menopause.org).

Address correspondence to: JoAnn V. Pinkerton, MD, Box 801104, University of Virginia Health System, Charlottesville, VA 22908. E-mail: jvp9u@virginia.edu

© 2014 by The North American Menopause Society.