Two-Way Randomized Crossover Study to Establish Pharmacodynamic Bioequivalence Between Oxylanthanum Carbonate and Lanthanum Carbonate

IF 3.2 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Vandana Mathur MD, FASN , Michael Walker PhD , Steve Hasal PhD , Guru Reddy PhD , Shalabh Gupta MD
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引用次数: 0

Abstract

Purpose

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.

Methods

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).

Findings

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.

Implications

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.

Clinical Trial Registration Number

NCT06218290.
建立碳酸氧镧和碳酸镧之间药效学生物等效性的双向随机交叉研究。
目的:磷酸盐结合剂(PB)是治疗终末期肾病患者高磷血症不可或缺的药物。不依从性和相对于饮食摄入的磷酸盐结合能力有限会对PB的功效产生不利影响。碳酸氧镧是一种正在研究的新型纳米技术产品,它将镧与可用PBs的最高结合能力结合在一起,并将其与较小的药丸尺寸结合在一起,可以用水吞下而不是咀嚼。本研究的目的是证明口服碳酸氧镧与碳酸镧(LC)在健康受试者体内的药效学等效性。方法:在这项单中心、随机、开放标签的一期研究中,采用双向交叉设计,健康受试者分别服用碳酸氧镧可吞片1000 mg / 3次/天和LC咀嚼片1000 mg / 3次/天。主要药效学变量是尿磷酸盐排泄从基线到评估期(治疗1-4天)的最小二乘平均值(LSM)变化。结果:共有80名受试者被随机分配,其中75人接受了所有剂量。从基线到评估(治疗)期尿磷酸盐排泄的LSM变化在碳酸氧镧组(-320.4 mg/天[90% CI: -349.7, -291.0])和LC组(-324.0 mg/天[90% CI: -353.3, -294.7])中相似;两组间LSM差异为3.6 mg/d [90% CI: -37.8, 45.1]。两种药物耐受性良好,不良事件发生率相等。因此,碳酸氧镧在健康受试者中与LC具有生物等效性,并且耐受性良好。口服碳酸氧镧可能为慢性肾脏疾病和高磷血症患者提供一种选择,他们不喜欢咀嚼片剂,不方便或困难。临床试验注册号:NCT06218290。
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
Clinical therapeutics
Clinical therapeutics 医学-药学
CiteScore
6.00
自引率
3.10%
发文量
154
审稿时长
9 weeks
期刊介绍: Clinical Therapeutics provides peer-reviewed, rapid publication of recent developments in drug and other therapies as well as in diagnostics, pharmacoeconomics, health policy, treatment outcomes, and innovations in drug and biologics research. In addition Clinical Therapeutics features updates on specific topics collated by expert Topic Editors. Clinical Therapeutics is read by a large international audience of scientists and clinicians in a variety of research, academic, and clinical practice settings. Articles are indexed by all major biomedical abstracting databases.
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