Mathur Vandana, Walker Michael, Hasal Steve, Reddy Guru, Gupta Shalabh
Mathur Consulting, LLC, Woodside, CA.
Independent Consultant, Biostatistics, San Diego, CA.
Clin Ther. 2025 Jan;47(1):70-75. doi: 10.1016/j.clinthera.2024.11.009. Epub 2024 Nov 30.
Phosphate binders (PB) are integral to hyperphosphatemia management in patients with end-stage kidney disease. PB efficacy is adversely affected by nonadherence and limited phosphate-binding capacity relative to dietary intake. Oxylanthanum carbonate is an investigational novel nanotechnology product that combines lanthanum, which has the highest binding capacity of available PBs, with a smaller pill size that is swallowed with water rather than chewed. This study's objective was to demonstrate the pharmacodynamic equivalence of orally administered oxylanthanum carbonate to lanthanum carbonate (LC) in healthy subjects.
In this phase one, single-center, randomized, open-label study, healthy subjects were treated with oxylanthanum carbonate swallowable tablets 1000 mg three times/day and LC chewable tablets 1000 mg three times/day in a two-way crossover design. The primary pharmacodynamic variable was the least squares mean (LSM) change in urinary phosphate excretion from baseline to the evaluation period (Days 1-4 of treatment).
A total of 80 subjects were randomized and 75 received all doses. The LSM change in urinary phosphate excretion from Baseline to the Evaluation (Treatment) Period was similar for both oxylanthanum carbonate (-320.4 mg/day [90% CI: -349.7, -291.0]) and LC (-324.0 mg/day [90% CI: -353.3, -294.7]); the between-group LSM difference was 3.6 [90% CI: -37.8, 45.1] mg/day. Both drugs were well tolerated with an equal incidence of adverse events.
Thus, oxylanthanum carbonate was bioequivalent to LC in healthy subjects and well tolerated. Oral oxylanthanum carbonate may provide an option for patients with chronic kidney disease and hyperphosphatemia for whom chewing tablets is disliked, inconvenient, or difficult.
NCT06218290.
磷酸盐结合剂（PB）是终末期肾病患者高磷血症管理的重要组成部分。PB的疗效受到不依从性的不利影响，并且相对于饮食摄入量，其磷酸盐结合能力有限。氧化镧碳酸盐是一种研究中的新型纳米技术产品，它将镧（现有PB中结合能力最高的）与较小的药丸尺寸相结合，可随水吞服而非咀嚼。本研究的目的是在健康受试者中证明口服氧化镧碳酸盐与碳酸镧（LC）的药效学等效性。
在这项单中心、随机、开放标签的一期研究中，健康受试者采用双向交叉设计，接受每日三次、每次1000毫克的氧化镧碳酸盐可吞咽片剂和每日三次、每次1000毫克的LC咀嚼片剂治疗。主要药效学变量是从基线到评估期（治疗第1 - 4天）尿磷排泄的最小二乘均值（LSM）变化。
共有80名受试者被随机分组，75名接受了所有剂量。氧化镧碳酸盐（-320.4毫克/天[90%置信区间：-349.7，-291.0]）和LC（-324.0毫克/天[90%置信区间：-353.3，-294.7]）从基线到评估（治疗）期的尿磷排泄LSM变化相似；组间LSM差异为3.6[90%置信区间：-37.8，45.1]毫克/天。两种药物耐受性良好，不良事件发生率相同。
因此，氧化镧碳酸盐在健康受试者中与LC生物等效且耐受性良好。口服氧化镧碳酸盐可能为不喜欢咀嚼片剂、觉得咀嚼片剂不方便或困难的慢性肾病和高磷血症患者提供一种选择。
NCT06218290。
