Efficacy and safety of evocalcet in Japanese peritoneal dialysis patients

Kazuhiko Tsuruya, Ryutaro Shimazaki, Masafumi Fukagawa, Tadao Akizawa, Evocalcet Study Group, Yoshimitsu Hayashi, Hidetomo Nakamoto, Shoji Koga, Ichiro Okido, Minoru Kubota, Fumihiko Koiwa, Masahiro Takeda, Terumasa Hayashi, Makoto Hiramatsu, Hideki Kawanishi, Hidetoshi Kanai, Sakuya Ito, Kazuhiko Tsuruya, Koji Mitsuiki, Hirofumi Ikeda, Kazuhiko Tsuruya, Ryutaro Shimazaki, Masafumi Fukagawa, Tadao Akizawa, Evocalcet Study Group, Yoshimitsu Hayashi, Hidetomo Nakamoto, Shoji Koga, Ichiro Okido, Minoru Kubota, Fumihiko Koiwa, Masahiro Takeda, Terumasa Hayashi, Makoto Hiramatsu, Hideki Kawanishi, Hidetoshi Kanai, Sakuya Ito, Kazuhiko Tsuruya, Koji Mitsuiki, Hirofumi Ikeda

Abstract

Background: Secondary hyperparathyroidism (SHPT) is a serious and common complication in patients receiving peritoneal dialysis (PD). Cinacalcet is currently the recommended therapy for SHPT; however, gastrointestinal (GI)-related symptoms can result in low adherence and high discontinuation rates. Evocalcet is a novel calcimimetic agent that has non-inferior efficacy while providing a more tolerable safety profile.

Methods: This was a multicenter, intra-subject dose-adjustment treatment study evaluating the efficacy and safety of 1-8 mg evocalcet orally administered once daily for 32 weeks for the treatment of SHPT in PD patients. Patients then entered a 20-week extension period (dose range 1-12 mg). The primary endpoint was the proportion of patients who achieved a mean intact parathyroid hormone (iPTH) level of 60-240 pg/mL during the evaluation period (weeks 30-32). Secondary efficacy endpoints included the proportion of patients achieving ≥ 30% decrease in iPTH levels.

Results: A total of 39 Japanese PD patients with SHPT received evocalcet. The target mean iPTH level of 60-240 pg/mL was achieved by 71.8% (28/39) of patients during the evaluation period and 83.3% (20/24) of patients at week 52. The proportion of patients who achieved ≥ 30% decrease in iPTH levels from baseline was 74.4% (29/39) during the evaluation period and 87.5% (21/24) at week 52. Adverse drug reactions occurred in 46.2% (18/39) of patients, with most being of mild-to-moderate severity including GI-related events.

Conclusion: This study shows the long-term efficacy and safety of evocalcet when orally administered to PD patients with SHPT once daily.

Clinical trial registration: ClinicalTrials.gov: NCT02549417, https://ichgcp.net/clinical-trials-registry/NCT02549417 ; JAPIC: JapicCTI-153016, http://www.clinicaltrials.jp/user/showCteDetailE.jsp?japicId=JapicCTI-153016 .

Keywords: Calcimimetic; Evocalcet; Parathyroid hormone; Peritoneal dialysis; Phase III study; Secondary hyperparathyroidism.

Conflict of interest statement

We have read and understood Clinical and Experimental Nephrology’s policy on disclosing conflicts of interest and declare the following interests: KT has received consulting fees from Astellas Pharma Inc.; lecture fees from Kyowa Hakko Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Torii Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd.; and grants from Kyowa Hakko Kirin Co., Ltd. and Chugai Pharmaceutical Co., Ltd. MF has received consulting fees from Kyowa Hakko Kirin Co., Ltd. and Ono Pharmaceutical Co., Ltd.; lecture fees from Kyowa Hakko Kirin Co., Ltd., Bayer Yakuhin, Ltd., Torii Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd.; and grants from Kyowa Hakko Kirin Co., Ltd. and Bayer Yakuhin, Ltd. TA has received consulting fees from Kyowa Hakko Kirin Co., Ltd., Astellas Pharma Inc., Bayer Yakuhin, Ltd., Fuso Pharmaceutical Industries, Ltd., Japan Tobacco Inc., Ono Pharmaceutical Co., Ltd. and NIPRO Industry, and lecture fees from Kyowa Hakko Kirin Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Kissei Pharmaceutical Co., Ltd., Torii Pharmaceutical Co., Ltd. and Ono Pharmaceutical Co., Ltd. RS is employed by Kyowa Hakko Kirin Co., Ltd., which funded this research.

Figures

Fig. 1
Fig. 1
Study design (a) and patient flow diagram (b). FAS full analysis set
Fig. 2
Fig. 2
Time course of evocalcet dose distribution and mean daily dose during the study
Fig. 3
Fig. 3
Time-course change in intact parathyroid hormone (iPTH) levels (a), corrected serum calcium levels (b), and serum phosphorus levels (c) during the study. Data are shown as mean ± SD. SD standard deviation

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