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

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.