caa a22 4500 605462844 CHVBK 20210128100250.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00774-013-0558-2 doi (NATIONALLICENCE)springer-10.1007/s00774-013-0558-2 Bone turnover markers and pharmacokinetics of a new sustained-release formulation of the cathepsin K inhibitor, ONO-5334, in healthy post-menopausal women [Elektronische Daten] [Shinichi Nagase, Michiyo Ohyama, Yoshitaka Hashimoto, Maria Small, John Sharpe, Junichiro Manako, Tomohiro Kuwayama, Steve Deacon] A sustained-release tablet (SRT) of ONO-5334 was compared to the immediate-release tablet (IRT) dose, which demonstrated effects on bone mineral density (BMD) comparable to those of therapy with alendronate. The single-dose phase was a randomized, partial single-blind, crossover study where 50-, 100-, and 300-mg SRTs and 300-mg IRTs were administered to nine post-menopausal women. The multiple-dose phase was a randomized, double-blind, placebo-controlled, parallel-group study where 100- and 300-mg SRTs, or placebo were administered to 24 women. After a single administration of a 300-mg SRT, mean C max was 3.3-fold lower, mean AUCinf was 0.83-fold lower and mean C 24h was 5.4-fold higher compared to the 300-mg IRT. Repeated SRT dosing did not significantly affect PK, although C 24h increased slightly. After a single ONO-5334 dose, serum CTX-I was suppressed by ~50% within 1h, reaching maximum suppression 6h post-dose. Greater suppression was maintained longer by the 300-mg SRT vs. the 300-mg IRT. Second morning void and cumulative urine CTX-I showed clear dose-response effects at/over 24h for SRT, with maximum suppression occurring at/over 24h (except 50- and 300-mg cumulative urine). Repeated dosing suggested greater suppression of urine CTX-I. Compared with the IRT, the SRT showed reduced C max, greater C 24h, and slightly reduced AUCinf dose for dose. The SRT showed clear dose-response suppression on bone resorption and greater efficacy dose for dose vs. the IRT. The Japanese Society for Bone and Mineral Research and Springer Japan, 2014 Cathepsin K inhibitor nationallicence Osteoporosis nationallicence Sustained-release formulation nationallicence CTX-I nationallicence ONO-5334 nationallicence Nagase Shinichi Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut Ohyama Michiyo Clinical Development Planning, Ono Pharmaceutical Co., Ltd., 8-2, Kyutaromachi, Chuo-ku, 1-chome, 541-8564, Osaka, Japan aut Hashimoto Yoshitaka Pharmacokinetic Research Group, Ono Pharmaceutical Co., Ltd., 17-2 Wadai, 300-4247, Tsukuba, Ibaraki, Japan aut Small Maria Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut Sharpe John Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut Manako Junichiro Clinical Development Planning, Ono Pharmaceutical Co., Ltd., 8-2, Kyutaromachi, Chuo-ku, 1-chome, 541-8564, Osaka, Japan aut Kuwayama Tomohiro Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut Deacon Steve Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut Journal of Bone and Mineral Metabolism Springer Japan 33/1(2015-01-01), 93-100 0914-8779 33:1<93 2015 33 774 https://doi.org/10.1007/s00774-013-0558-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00774-013-0558-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nagase Shinichi Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut NATIONALLICENCE 700 1- Ohyama Michiyo Clinical Development Planning, Ono Pharmaceutical Co., Ltd., 8-2, Kyutaromachi, Chuo-ku, 1-chome, 541-8564, Osaka, Japan aut NATIONALLICENCE 700 1- Hashimoto Yoshitaka Pharmacokinetic Research Group, Ono Pharmaceutical Co., Ltd., 17-2 Wadai, 300-4247, Tsukuba, Ibaraki, Japan aut NATIONALLICENCE 700 1- Small Maria Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut NATIONALLICENCE 700 1- Sharpe John Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut NATIONALLICENCE 700 1- Manako Junichiro Clinical Development Planning, Ono Pharmaceutical Co., Ltd., 8-2, Kyutaromachi, Chuo-ku, 1-chome, 541-8564, Osaka, Japan aut NATIONALLICENCE 700 1- Kuwayama Tomohiro Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut NATIONALLICENCE 700 1- Deacon Steve Drug Development, ONO PHARMA UK LTD, MidCity Place, 71 High Holborn, WC1V 6EA, London, UK aut NATIONALLICENCE 773 0- Journal of Bone and Mineral Metabolism Springer Japan 33/1(2015-01-01), 93-100 0914-8779 33:1<93 2015 33 774