Yasuhiro Takeuchi1,2, Yuichi Nishida3, Yuichiro Kondo3, Yasuo Imanishi4, Seiji Fukumoto5. 1. Toranomon Hospital Endocrine Center, 2-2-2, Toranomon, Minato-ku, Tokyo, 105-8470, Japan. takeuchi-tky@umin.ac.jp. 2. Okinaka Memorial Institute for Medical Research, Tokyo, Japan. takeuchi-tky@umin.ac.jp. 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.
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.
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.