Evocalcet in patients with primary hyperparathyroidism: an open-label, single-arm, multicenter, 52-week, dose-titration
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ORIGINAL ARTICLE
Evocalcet in patients with primary hyperparathyroidism: an open‑label, single‑arm, multicenter, 52‑week, dose‑titration phase III study Yasuhiro Takeuchi1,2 · Yuichi Nishida3 · Yuichiro Kondo3 · Yasuo Imanishi4 · Seiji Fukumoto5 Received: 24 December 2019 / Accepted: 4 March 2020 © The Japanese Society Bone and Mineral Research and Springer Japan KK, part of Springer Nature 2020
Abstract Introduction Primary hyperparathyroidism (PHPT) is caused by parathyroid adenoma, primary parathyroid hyperplasia, or parathyroid carcinoma. For some patients with PHPT controlling serum calcium levels is critical. Materials and methods We conducted an open-label, single-arm, 52-week, phase III study in Japanese patients with hypercalcemia due to PHPT to demonstrate efficacy and safety of evocalcet, a new calcimimetic. Patients with intractable PHPT (n = 13), postsurgical recurrence (n = 2), and parathyroid carcinoma (n = 3) were enrolled. Evocalcet administration started at a dose of 2 mg once or twice daily and was titrated to achieve the target serum corrected calcium (cCa) concentration (≤ 10.3 mg/dL) for two consecutive weeks (maximal dose 24 mg/day). Results Fourteen patients achieved the target (77.8%; 95% confidence interval [CI] 52.4–93.6). The lower limit of 95% CI exceeded the predetermined reference limit (11%), and thus, efficacy was confirmed. Of 18 patients, 12 (66.7%; 95% CI 41.0–86.7) showed decreased serum cCa of ≥ 1.0 mg/dL from the baseline for two consecutive weeks during the titration phase. Sixteen patients entered the maintenance phase, and 15 patients completed the study. Treatment-emergent adverse events (TEAEs) were recorded in 18/18 patients (100%) and drug-related TEAEs in 8/18 (44.4%). The most commonly observed drug-related TEAE was nausea (2/18 patients). No unexpected drug-related TEAEs were observed. All drug-related TEAEs were mild in severity. No patient discontinued the study because of drug-related TEAEs. Conclusion Evocalcet demonstrated long-term effectiveness in reducing serum cCa concentrations and safety without any unexpected drug-related TEAEs in PHPT patients. Keywords Primary hyperparathyroidism · Parathyroid carcinoma · Calcimimetic · Hypercalcemia · Evocalcet
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00774-020-01097-y) contains supplementary material, which is available to authorized users. * Yasuhiro Takeuchi takeuchi‑[email protected] 1
Toranomon Hospital Endocrine Center, 2‑2‑2, Toranomon, Minato‑ku, Tokyo 105‑8470, Japan
2
Okinaka Memorial Institute for Medical Research, Tokyo, Japan
3
Kyowa Kirin Co., Ltd, Tokyo, Japan
4
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
5
Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan
Introduction Primary hyperparathyroidism (PHPT) is an endocrine disorder exhibiting hypercalcemia. Its cause
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