erteberel and Prostatic-Hyperplasia

To assess the efficacy and safety of LY500307, a selective estrogen receptor beta agonist, on lower urinary tract symptoms (LUTS) in patients with enlarged prostate secondary to BPH.. In a randomized, double-blind, placebo-controlled, parallel phase 2, efficacy and safety study, eligible patients with moderate to severe LUTS and prostatic enlargement (⩾30 ml) were randomized to placebo or LY500307 at 1, 3, 10 and 25 mg once daily for 24 weeks. Primary efficacy end point was change in total International Prostate Symptoms Score (IPSS) after 24 weeks. Secondary end points included changes in total prostate volume (TPV) that served as a proof of concept end point, as well as IPSS quality of life, maximum peak urine flow rate (Qmax) and PSA and safety (adverse events, laboratory test).. A total of 414 patients were randomized when the study was terminated because of insufficient TPV reduction, based on a priori defined interim analysis. The IPSS mean change from baseline to end point was -3.4±6.8 in the placebo group and -1.3±6.6, -2.6±7.0, -3.7±6.7 and -4.4±5.7 in the 1, 3, 10 and 25 mg LY500307-treated groups, respectively (P>0.05). Similarly, no treatment effect was observed for any of the secondary efficacy measures. Incidence of adverse events was comparable between treatment groups, and no clinically meaningful changes in laboratory tests were observed.. LY500307 was well tolerated in BPH patients with LUTS at doses up to 25 mg once daily for 24 weeks. The study was terminated early because of inadequate efficacy.

Topics: Aged; Aged, 80 and over; Benzopyrans; Estrogen Receptor beta; Humans; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Quality of Life; Urinary Tract

Benzopyran selective estrogen receptor beta agonist-1 (SERBA-1) shows potent, selective binding and agonist function in estrogen receptor beta (ERbeta) in vitro assays. X-ray crystal structures of SERBA-1 in ERalpha and beta help explain observed beta-selectivity of this ligand. SERBA-1 in vivo demonstrates involution of the ventral prostate in CD-1 mice (ERbeta effect), while having no effect on gonadal hormone levels (ERalpha effect) at 10x the efficacious dose, consistent with in vitro properties of this molecule.

Topics: Animals; Binding Sites; Crystallography, X-Ray; Estrogen Receptor alpha; Estrogen Receptor beta; Estrogens; Flavonoids; Humans; Ligands; Male; Mice; Models, Molecular; Molecular Structure; Prostate; Prostatic Hyperplasia; Selective Estrogen Receptor Modulators; Structure-Activity Relationship