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

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.

• Authors: Gary Hattersley, Alan G Harris, James A Simon, Ginger D Constantine
• Journal: Menopause (New York, N.Y.) (Menopause) Vol. 24 Issue 1 Pg. 92-99 (01 2017) ISSN: 1530-0374 [Electronic] United States
• PMID: 27575546 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• RAD1901
• Selective Estrogen Receptor Modulators
• Tetrahydronaphthalenes

Topics

• Adult
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Hot Flashes (drug therapy)
• Humans
• Ligands
• Middle Aged
• Postmenopause (physiology)
• Selective Estrogen Receptor Modulators (administration & dosage, blood)
• Severity of Illness Index
• Tetrahydronaphthalenes (therapeutic use)
• Treatment Outcome
• Vasomotor System (drug effects)