一项评估碳酸镧在接受透析治疗的高磷血症慢性肾脏病儿童和青少年中的疗效、安全性和药代动力学的开放标签 2 期临床试验。

An open-label phase 2 trial to assess the efficacy, safety and pharmacokinetics of lanthanum carbonate in hyperphosphatemic children and adolescents with chronic kidney disease undergoing dialysis.

机构信息

Department of Pediatrics and Nephrology, Faculty of Medicine, Medical University of Bialystok, University Children's Clinical Hospital of Bialystok, Waszyngtona, Bialystok, Poland.

Shire Human Genetic Therapies, Inc., a Takeda Company, Cambridge, MA, USA.

出版信息

BMC Nephrol. 2022 Mar 2;23(1):84. doi: 10.1186/s12882-022-02688-9.

DOI:10.1186/s12882-022-02688-9

PMID:35236302

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8892701/

Abstract

BACKGROUND

This study assessed the efficacy, tolerability and pharmacokinetics (PK) of lanthanum carbonate (LC) in hyperphosphatemic children and adolescents with chronic kidney disease (CKD) undergoing dialysis.

METHODS

This was a three-part, multicenter, open-label study of LC (oral powder formulation) in patients 10 to < 18 years old with CKD undergoing dialysis. In part 1, the single-dose PK of LC (500 mg, ≤12 years old; 1000 mg, > 12 years old) were summarized. In part 2, patients received calcium carbonate (CC [chewable tablet formulation]) (1500-6500 mg [total daily dose]) followed by LC (powder formulation) (1500-3000 mg [total daily dose]), or LC only (1500-3000 mg [total daily dose]), each for 8 weeks. During part 3, patients received LC (1500-3000 mg [total daily dose]) for up to 6 months. The primary efficacy endpoint was the proportion of LC-treated patients achieving serum phosphorus control after 8 weeks during parts 2 and/or 3, defined as: ≤1.94 mmol/L, < 12 years old; ≤1.78 mmol/L, ≥12 years old. Secondary efficacy endpoints included: the proportion of patients who achieved serum phosphorus control after 8 weeks of treatment with CC followed by 8 weeks of treatment with LC (with a washout period between treatments). The safety of LC and CC was also evaluated.

RESULTS

In part 1, 20 patients received a single dose of LC. In part 2, 53 and 51 patients were treated with CC and LC for 8 weeks, respectively. During part 3, 42 patients received LC for up to 6 months. Most patients were white and male. For the primary efficacy endpoint, 50% (17/34) of patients who received LC for 8 weeks during parts 2 and/or 3 achieved serum phosphorus control. After 8 weeks of treatment with CC, 58.8% of patients achieved serum phosphorus control; after a subsequent washout period and 8 weeks of treatment with LC, 70.6% of patients achieved serum phosphorus control. T and t occurred within 3-8 h and ~ 19 h, respectively; however, variability was observed. LC and CC were generally well tolerated.

CONCLUSIONS

These data support the use of LC to manage hyperphosphatemia in pediatric patients with CKD undergoing dialysis.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT01696279; EudraCT identifier: 2012-000171-17. Date of registration: 01/10/2012.

摘要

背景

本研究评估了碳酸镧（LC）在接受透析的慢性肾脏病（CKD）儿童和青少年高磷血症患者中的疗效、耐受性和药代动力学（PK）。

方法

这是一项三部分、多中心、开放性研究，评估了接受透析的 10 至 <18 岁 CKD 患者使用 LC（口服粉末制剂）的情况。在第 1 部分中，总结了 LC（500mg，≤12 岁；1000mg，>12 岁）的单次剂量 PK。在第 2 部分中，患者接受碳酸钙（CC [咀嚼片制剂]）（1500-6500mg[总日剂量]）治疗，随后接受 LC（粉末制剂）（1500-3000mg[总日剂量]）或仅 LC（1500-3000mg[总日剂量]）治疗，各治疗 8 周。在第 3 部分中，患者接受 LC（1500-3000mg[总日剂量]）治疗长达 6 个月。主要疗效终点是第 2 和/或第 3 部分中 8 周时接受 LC 治疗的患者达到血清磷控制的比例，定义为：≤1.94mmol/L，≤12 岁；≤1.78mmol/L，≥12 岁。次要疗效终点包括：CC 治疗 8 周后再接受 LC 治疗 8 周的患者中达到血清磷控制的比例（治疗之间有洗脱期）。还评估了 LC 和 CC 的安全性。

结果

在第 1 部分中，20 名患者接受了单次 LC 剂量。在第 2 部分中，53 名和 51 名患者分别接受 CC 和 LC 治疗 8 周。在第 3 部分中，42 名患者接受 LC 治疗长达 6 个月。大多数患者为白人且为男性。对于主要疗效终点，在第 2 和/或第 3 部分接受 8 周 LC 治疗的 34 名患者中有 50%（17/34）达到血清磷控制。CC 治疗 8 周后，58.8%的患者达到血清磷控制；随后洗脱期后再接受 8 周 LC 治疗，70.6%的患者达到血清磷控制。T 和 t 分别在 3-8 小时和~19 小时内发生；然而，存在变异性。LC 和 CC 通常耐受性良好。