Evocalcet in patients with primary hyperparathyroidism: an open-label, single-arm, multicenter, 52-week, dose-titration phase III study
Evocalcet in patients with primary hyperparathyroidism: an open-label, single-arm, multicenter, 52-week, dose-titration phase III study
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DOI：
10.1007/s00774-020-01097-y
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发表时间：
2020-04-09
影响因子：
3.3
通讯作者：
Fukumoto, Seiji
中科院分区：
文献类型：
--
作者：
Takeuchi, Yasuhiro;Nishida, Yuichi;Fukumoto, Seiji
原发性甲状旁腺功能亢进（PHPT）是由甲状旁腺腺瘤、原发性甲状旁腺增生或甲状旁腺癌引起的疾病。对于一些PHPT患者，控制血钙水平是至关重要的。材料和方法我们在日本PHPT高钙血症患者中进行了一项开放标签、单组、52周的III期研究，以证明evocalcet（一种新的钙化剂）的有效性和安全性。纳入顽固性PHPT （n = 13）、术后复发（n = 2）和甲状旁腺癌（n = 3）患者。Evocalcet起始剂量为2mg，每日1次或2次，在滴定阶段连续两周滴定至达到血清校正钙（cCa）的目标浓度（从基线开始= 1.0 mg/dL）。16名患者进入维持期，15名患者完成研究。18例患者中有18例（100%）记录了治疗引起的不良事件（teae）， 8例（44.4%）记录了药物相关的teae。最常见的药物相关性TEAE是恶心（2/18）。未观察到意外的药物相关teae。所有药物相关teae的严重程度均为轻度。没有患者因为药物相关性teae而中断研究。结论Evocalcet在降低PHPT患者血清cCa浓度方面具有长期有效性，且安全性高，无意外药物相关teae。
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 (= 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.