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Clinical investigation of RAD1901, a novel estrogen receptor ligand, for the treatment of postmenopausal vasomotor symptoms: a phase 2 randomized, placebo-controlled, double-blind, dose-ranging, proof-of-concept trial

Hattersley, Gary PhD; Harris, Alan G. MD; Simon, James A. MD; Constantine, Ginger D. MD

doi: 10.1097/GME.0000000000000726
Original Articles

Objective: The aim of the study was to assess the efficacy and safety of RAD1901, an oral estrogen receptor ligand, for the treatment of moderate-to-severe vasomotor symptoms of menopause.

Methods: This was a randomized, placebo-controlled, double-blind, dose-ranging, proof-of-concept trial. Postmenopausal women with a minimum of 7 moderate-to-severe, diary-reported hot flashes per day, or 50 per week, were randomized to one of five blinded dose groups (0 [placebo], 10, 25, 50, or 100 mg RAD1901 daily for 28 d). Efficacy endpoints included frequency and severity of hot flashes over 4 weeks of treatment.

Results: One hundred participants were randomized across the five treatment regimens. The frequency of moderate-to-severe hot flashes decreased in all groups over the treatment period (mean percent change from baseline at 4 wk, −54.1%, −77.2%, −51.8%, −53.8%, and −67.0% for placebo, 10, 25, 50, and 100 mg groups). The response in the 10 mg group was significantly different from placebo at 4 weeks (P = 0.024). No other dose group was significantly different from placebo. There were no statistically significant differences in severity of hot flashes between placebo and any dose group. Treatment was well tolerated; most treatment-emergent adverse events were mild to moderate in severity.

Conclusions: Daily treatment with 10 mg RAD1901 over 4 weeks resulted in a statistically significant reduction in the frequency of moderate-to-severe hot flashes compared with placebo, with an acceptable safety profile. Further clinical trials are warranted to investigate RAD1901's utility as a potential treatment for vasomotor symptoms.

1Radius Health, Inc, Waltham, MA

2Women's Health & Research Consultants, Washington, DC

3EndoRheum Consultants LLC, Malvern, PA.

Address correspondence to: Alan G. Harris, MD, Radius Health, Inc, 950 Winter St, Waltham, MA 02451. E-mail: aharris@radiuspharm.com

Received 2 March, 2016

Revised 15 June, 2016

Accepted 15 June, 2016

Funding/support: Financial support was provided by Radius Health, Inc.

Clinical trial registration: Clinicaltrials.gov, NCT00875420.

Financial disclosure/conflicts of interest: G.H. and A.G.H. are employees of Radius Health, Inc and have stock options; J.A.S. has served (within the last year) or is currently serving as a consultant to or on the advisory boards of: AbbVie, Inc, Allergan, Plc, AMAG Pharmaceuticals, Inc, Amgen Inc, Apotex, Inc, Ascend Therapeutics, JDS Therapeutics, LLC, Merck & Co, Inc, Noven Pharmaceuticals, Inc, Novo Nordisk, Nuelle, Inc, Perrigo Company, PLC, Radius Health, Inc, Regeneron Pharmaceuticals, Inc, Roivant Sciences, Inc, Sanofi SA, Sermonix Pharmaceuticals, Inc, Shionogi Inc, Sprout Pharmaceuticals, Symbiotec Pharmalab, TherapeuticsMD, Valeant Pharmaceuticals; and has also served (within the last year) or is currently serving on the speaker's bureaus of: Amgen Inc, Eisai, Inc, Merck, Noven Pharmaceuticals, Inc, Novo Nordisk, Shionogi Inc, Valeant Pharmaceuticals; and in the last year has received or is currently receiving grant/research support from: AbbVie, Inc, Actavis, PLC, Agile Therapeutics, Bayer Healthcare LLC, New England Research Institute, Inc, Novo Nordisk, Palatin Technologies, Symbio Research, Inc, TherapeuticsMD; and is a stockholder (direct purchase) in Sermonix Pharmaceuticals; G.D.C. consults to multiple pharmaceutical companies, including but not limited to Radius Health, Inc.

© 2017 by The North American Menopause Society.