C G Roehrborn1, M E Spann2, S L Myers2, C R Serviss2, L Hu2, Y Jin2. 1. UT Southwestern Medical Center at Dallas, Dallas, TX, USA. 2. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
Abstract
BACKGROUND: 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. METHODS: 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). RESULTS: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. CONCLUSIONS: 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.
RCT Entities:
BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: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.
Authors: Michael Marberger; Claus G Roehrborn; Leonard S Marks; Timothy Wilson; Roger S Rittmaster Journal: J Clin Endocrinol Metab Date: 2006-01-24 Impact factor: 5.958
Authors: Bryan H Norman; Jeffrey A Dodge; Timothy I Richardson; Peter S Borromeo; Charles W Lugar; Scott A Jones; Keyue Chen; Yong Wang; Gregory L Durst; Robert J Barr; Chahrzad Montrose-Rafizadeh; Harold E Osborne; Robert M Amos; Sherry Guo; Amechand Boodhoo; Venkatesh Krishnan Journal: J Med Chem Date: 2006-10-19 Impact factor: 7.446
Authors: John D McConnell; Claus G Roehrborn; Oliver M Bautista; Gerald L Andriole; Christopher M Dixon; John W Kusek; Herbert Lepor; Kevin T McVary; Leroy M Nyberg; Harry S Clarke; E David Crawford; Ananias Diokno; John P Foley; Harris E Foster; Stephen C Jacobs; Steven A Kaplan; Karl J Kreder; Michael M Lieber; M Scott Lucia; Gary J Miller; Mani Menon; Douglas F Milam; Joe W Ramsdell; Noah S Schenkman; Kevin M Slawin; Joseph A Smith Journal: N Engl J Med Date: 2003-12-18 Impact factor: 91.245
Authors: Otabek Imamov; Andrea Morani; Gil-Jin Shim; Yoko Omoto; Christina Thulin-Andersson; Margaret Warner; Jan-Ake Gustafsson Journal: Proc Natl Acad Sci U S A Date: 2004-06-08 Impact factor: 11.205
Authors: Claus G Roehrborn; Paul Siami; Jack Barkin; Ronaldo Damião; Kim Major-Walker; Betsy Morrill; Francesco Montorsi Journal: J Urol Date: 2007-12-21 Impact factor: 7.450
Authors: Nienke Moret; Nicholas A Clark; Marc Hafner; Yuan Wang; Eugen Lounkine; Mario Medvedovic; Jinhua Wang; Nathanael Gray; Jeremy Jenkins; Peter K Sorger Journal: Cell Chem Biol Date: 2019-04-04 Impact factor: 8.116
Authors: Wan-Fu Wu; Laure Maneix; Jose Insunza; Ivan Nalvarte; Per Antonson; Juha Kere; Nancy Yiu-Lin Yu; Virpi Tohonen; Shintaro Katayama; Elisabet Einarsdottir; Kaarel Krjutskov; Yu-Bing Dai; Bo Huang; Wen Su; Margaret Warner; Jan-Åke Gustafsson Journal: Proc Natl Acad Sci U S A Date: 2017-04-24 Impact factor: 11.205
Authors: Kari B Wisinski; Wei Xu; Amye J Tevaarwerk; Sandeep Saha; KyungMann Kim; Anne Traynor; Leah Dietrich; Robert Hegeman; Dhimant Patel; Jules Blank; Josephine Harter; Mark E Burkard Journal: Clin Breast Cancer Date: 2016-03-31 Impact factor: 3.225
Authors: Teresa T Liu; Melanie J Grubisha; Krystle A Frahm; Stacy G Wendell; Jiayan Liu; William A Ricke; Richard J Auchus; Donald B DeFranco Journal: J Biol Chem Date: 2016-05-13 Impact factor: 5.157
Authors: Bin Yuan; Long Cheng; Kshama Gupta; Huai-Chin Chiang; Harshita B Gupta; Gangadhara R Sareddy; Degeng Wang; Kate Lathrop; Richard Elledge; Pei Wang; Stanton McHardy; Ratna Vadlamudi; Tyler J Curiel; Yanfen Hu; Qinong Ye; Rong Li Journal: Oncotarget Date: 2016-07-05
Authors: Gangadhara R Sareddy; Xiaonan Li; Jinyou Liu; Suryavathi Viswanadhapalli; Lauren Garcia; Aleksandra Gruslova; David Cavazos; Mike Garcia; Anders M Strom; Jan-Ake Gustafsson; Rajeshwar Rao Tekmal; Andrew Brenner; Ratna K Vadlamudi Journal: Sci Rep Date: 2016-04-29 Impact factor: 4.379