title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: 1Radius Health, Inc, Waltham, MA 2Women's Health & Research Consultants, Washington, DC 3EndoRheum Consultants LLC, Malvern, PA.
authors: Gary
authors: G
authors: Hattersley
authors: Alan G
authors: AG
authors: Harris
authors: James A
authors: JA
authors: Simon
authors: Ginger D
authors: GD
authors: Constantine
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D008024:Ligands; D008875:Middle Aged; D017698:Postmenopause / Q000502:physiology*; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000097:blood; D012720:Severity of Illness Index; D013764:Tetrahydronaphthalenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D014666:Vasomotor System / Q000187:drug effects*
chemical_list: D008024:Ligands; C000626184:RAD1901; D020845:Selective Estrogen Receptor Modulators; D013764:Tetrahydronaphthalenes