Open-label extension of a randomized trial investigating safety and efficacy of rhPTH(1–84) in hypoparathyroidism

IF 3.4 Q2 ENDOCRINOLOGY & METABOLISM
JBMR Plus Pub Date : 2024-01-05 DOI:10.1093/jbmrpl/ziad010
Aliya A Khan, Lisa G Abbott, Intekhab Ahmed, O. Ayodele, Claudia Gagnon, Richard D Finkelman, Emese Mezosi, Lars Rejnmark, Istvan Takacs, Shaoming Yin, Steven W Ing
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Abstract

Hypoparathyroidism is a rare disease, often inadequately controlled by conventional treatment. PARALLAX was a mandatory post-marketing trial assessing pharmacokinetics and pharmacodynamics of different dosing regimens of recombinant human parathyroid hormone 1–84 (rhPTH[1–84]) for treating hypoparathyroidism. The present study (NCT03364738) was a Phase 4, 1-year open-label extension of PARALLAX. Patients received only two doses of rhPTH(1–84) in PARALLAX and were thus considered treatment-naive at the start of the current study. rhPTH(1–84) was initiated at 50 μg once daily, with doses adjusted based on albumin-corrected serum calcium levels. Albumin-corrected serum calcium (primary outcome measure), health-related quality of life (HRQoL), adverse events, and healthcare resource utilization (HCRU) were assessed. The mean age of the 22 patients included was 50.0 years; 81.8% were women, and 90.9% were White. By end of treatment (EOT), 95.5% of patients had albumin-corrected serum calcium values in the protocol-defined primary endpoint range of 1.88 mmol/L to the upper limit of normal. Serum phosphorus was within the healthy range, and albumin-corrected serum calcium-phosphorus product was below the upper healthy limit throughout, while mean 24-hour urine calcium excretion decreased from baseline to EOT. Mean supplemental doses of calcium and active vitamin D were reduced from baseline to EOT (2402–855 mg/day and 0.8–0.2 μg/day, respectively). Mean serum bone turnover markers, bone-specific alkaline phosphatase, osteocalcin, procollagen type I N-terminal propeptide, and type I collagen C-telopeptide increased 2–5 fold from baseline to EOT. HCRU, disease-related symptoms and impact on HRQoL improved numerically between baseline and EOT. Nine patients (40.9%) experienced treatment-related adverse events; no deaths were reported. Treatment with rhPTH(1–84) once daily for 1 year improved HRQoL, maintained eucalcemia in 95% of patients, normalized serum phosphorus, and decreased urine calcium excretion. The effects observed on urine calcium and the safety profile are consistent with previous findings.
研究rhPTH(1-84)对甲状旁腺功能减退症的安全性和有效性的随机试验的开放标签扩展研究
甲状旁腺功能减退症是一种罕见疾病,常规治疗往往无法控制病情。PARALLAX是一项上市后强制试验,评估了重组人甲状旁腺激素1-84(rhPTH[1-84])治疗甲状旁腺功能减退症的不同剂量方案的药代动力学和药效学。本研究(NCT03364738)是PARALLAX的一项为期1年的第四期开放标签扩展研究。在PARALLAX研究中,患者只接受了两次rhPTH(1-84)治疗,因此在本研究开始时被视为未接受过治疗。对白蛋白校正血清钙(主要结局指标)、健康相关生活质量(HRQoL)、不良事件和医疗资源利用率(HCRU)进行了评估。22名患者的平均年龄为50.0岁,81.8%为女性,90.9%为白人。治疗结束(EOT)时,95.5% 的患者白蛋白校正血清钙值在方案定义的主要终点范围(1.88 mmol/L 至正常值上限)内。血清磷在健康范围内,白蛋白校正血清钙磷乘积始终低于健康上限,而平均 24 小时尿钙排泄量从基线到 EOT 均有所下降。从基线到 EOT,钙和活性维生素 D 的平均补充剂量有所减少(分别为 2402-855 毫克/天和 0.8-0.2 微克/天)。平均血清骨转换标志物、骨特异性碱性磷酸酶、骨钙素、I型胶原蛋白N末端前肽和I型胶原蛋白C-三肽从基线到EOT增加了2-5倍。从基线到 EOT,HCRU、疾病相关症状和对 HRQoL 的影响在数值上有所改善。九名患者(40.9%)出现了与治疗相关的不良事件;无死亡报告。rhPTH(1-84)治疗1年,每天1次,改善了患者的HRQoL,维持了95%患者的白细胞减少,使血清磷恢复正常,减少了尿钙排泄。观察到的对尿钙的影响和安全性与之前的研究结果一致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
JBMR Plus
JBMR Plus Medicine-Orthopedics and Sports Medicine
CiteScore
5.80
自引率
2.60%
发文量
103
审稿时长
8 weeks
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