title: Orally active prostacyclin analogue beraprost sodium in patients with chronic kidney disease: a randomized, double-blind, placebo-controlled, phase II dose finding trial.
abstract: BACKGROUND
  Evidence increasingly points to the importance of chronic hypoxia in the tubulointerstitium as a final common pathway to end-stage renal disease (ESRD). Beraprost sodium (BPS) is an orally active prostacyclin (PGI2) analogue demonstrating prevention of the progression of chronic kidney disease (CKD) in various animal models by maintaining renal blood flow and attenuating renal ischemic condition.
  
  
  METHODS
  This multicenter, randomized, double-blind, placebo-controlled, phase II trial was designed to determine the recommended dose of the sustained-release form of BPS (TRK-100STP 120 μg/day or 240 μg/day) in Japanese patients with CKD. TRK-100STP was administered to a total of 112 patients. The primary efficacy endpoint was the difference in the slope of the regression line of reciprocal of serum creatinine (1/SCr) over time, obtained by the least-squares method.
  
  
  RESULTS
  Regarding the primary endpoint, statistical superiority of TRK-100STP 240 μg over placebo was not confirmed and so a recommended dose was not determined. Compared to placebo, however, the slope of regression line of 1/SCr, elevation of SCr and serum cystatin C during the treatment period revealed greater improvement at 120 μg, at both doses, and at 240 μg, respectively. In terms of safety, both TRK-100STP treatment groups were well tolerated.
  
  
  CONCLUSIONS
  Although the study failed to meet the primary endpoint, results indicate that TRK-100STP may potentially prevent the decline in renal function of CKD patients independent of blood pressure or urinary protein levels.
  
  
  BACKGROUND
  NCT02480751. June 21, 2015.
authors.affiliation: University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8577, Japan. koyama.akio.dy@alumni.tsukuba.ac.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Koyama
authors.affiliation: Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8904, Japan. Toshiro.FUJITA@rcast.u-tokyo.ac.jp.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Niigata University, 1-757, Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan. gejyo@med.niigata-u.ac.jp.
authors.forename: Fumitake
authors.initials: F
authors.lastname: Gejyo
authors.affiliation: Division of Biostatistics and Clinical Epidemiology, Graduate School of Medicine and Pharmaceutical Sciences, The University of Toyama, 2630 Sugitani, Toyama City, 930-0194, Japan. horigasa@las.u-toyama.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Origasa
authors.affiliation: Toray Industries, Inc., 1-1, Nihonbashi-Muromachi 2-chome, Chuo-ku, Tokyo, 103-8666, Japan. Masanao_Isono2@nts.toray.co.jp.
authors.forename: Masanao
authors.initials: M
authors.lastname: Isono
authors.affiliation: Toray Industries, Inc., 1-1, Nihonbashi-Muromachi 2-chome, Chuo-ku, Tokyo, 103-8666, Japan. Hajimu_Kurumatani@nts.toray.co.jp.
authors.forename: Hajimu
authors.initials: H
authors.lastname: Kurumatani
authors.affiliation: Toray Industries, Inc., 1-1, Nihonbashi-Muromachi 2-chome, Chuo-ku, Tokyo, 103-8666, Japan. Kiyonobu_Okada@nts.toray.co.jp.
authors.forename: Kiyonobu
authors.initials: K
authors.lastname: Okada
authors.affiliation: Astellas Pharma Inc., 2-5-1 Nihonbashi-honcho, Chuo-ku, Tokyo, 103-8411, Japan. hiroyuki.kanoh@astellas.com.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kanoh
authors.affiliation: Astellas Pharma Inc., 2-5-1 Nihonbashi-honcho, Chuo-ku, Tokyo, 103-8411, Japan. takashi.kiriyama@astellas.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kiriyama
authors.affiliation: Astellas Pharma Inc., 2-5-1 Nihonbashi-honcho, Chuo-ku, Tokyo, 103-8411, Japan. shunsuke.yamada@astellas.com.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D003404:Creatinine / Q000097:blood* / Q000652:urine; D055316:Cystatin C / Q000097:blood; D003692:Delayed-Action Preparations; D018450:Disease Progression; D004311:Double-Blind Method; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D055316:Cystatin C; D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; C048081:beraprost; D003404:Creatinine; D011464:Epoprostenol