BACKGROUND:Phosphate binders are commonly used in tablet form to help patients with hyperphosphatemia limit their absorption of dietary phosphate. These patients frequently have a heavy tablet burden so alternative formulations provide choice and may support adherence. Lanthanum carbonate (LC) is a phosphate binder currently available as a chewable tablet. This study was conducted to support an application for marketing authorization for the oral powder formulation within the European Union. OBJECTIVE: The goal of this study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of an oral powder formulation of LC compared with the reference chewable tablet formulation. METHODS: A Phase I, single-center, randomized, open-label, 2-period, crossover study to assess pharmacodynamic equivalence of the 2 formulations was conducted in healthy adults aged 18 to 55 years receiving a diet standardized for phosphate content. Individuals were randomized to receive a different formulation in each period, taking 10 doses of 1000-mg LC at 3000 mg/d per period with an intervening washout of ≥14 days. The primary pharmacodynamic variable was mean daily excretion of urinary phosphorus over 3 days while receiving LC. Pharmacodynamic equivalence was confirmed if the 90% CI for the difference between formulations in least squares (LS) mean excreted urinary phosphorus was within ±20% of the LS mean value for the tablet formulation. Secondary end points included determination of pharmacokinetic parameters and assessment of tolerability by recording of adverse events. RESULTS: In total, 72 individuals entered the study. They were predominantly men (72.2%), with a mean (SD) age of 31.4 (8.26) years and a BMI of 25.8 (2.45) kg/m(2). The LS mean (SE) excreted urinary phosphorus was 16.8 (0.48) mmol/d during administration of LC tablets (±20% = ±3.35 mmol/d). The corresponding value during administration of LC oral powder was 15.2 (0.48) mmol/d; 90% CI for the difference between formulations was -2.38 to -0.82 mmol/d, confirming pharmacodynamic equivalence. The most common adverse events were gastrointestinal, and no serious adverse events were recorded. CONCLUSIONS: In this multiple-dose study, the oral powder and tablet formulations of LC were well tolerated and met the regulatory criteria for pharmacodynamic equivalence in these healthy volunteers. ClinicalTrials.gov identifier: NCT00880750.
RCT Entities:
BACKGROUND:Phosphate binders are commonly used in tablet form to help patients with hyperphosphatemia limit their absorption of dietary phosphate. These patients frequently have a heavy tablet burden so alternative formulations provide choice and may support adherence. Lanthanum carbonate (LC) is a phosphate binder currently available as a chewable tablet. This study was conducted to support an application for marketing authorization for the oral powder formulation within the European Union. OBJECTIVE: The goal of this study was to examine the pharmacodynamics, pharmacokinetics, and tolerability of an oral powder formulation of LC compared with the reference chewable tablet formulation. METHODS: A Phase I, single-center, randomized, open-label, 2-period, crossover study to assess pharmacodynamic equivalence of the 2 formulations was conducted in healthy adults aged 18 to 55 years receiving a diet standardized for phosphate content. Individuals were randomized to receive a different formulation in each period, taking 10 doses of 1000-mg LC at 3000 mg/d per period with an intervening washout of ≥14 days. The primary pharmacodynamic variable was mean daily excretion of urinary phosphorus over 3 days while receiving LC. Pharmacodynamic equivalence was confirmed if the 90% CI for the difference between formulations in least squares (LS) mean excreted urinary phosphorus was within ±20% of the LS mean value for the tablet formulation. Secondary end points included determination of pharmacokinetic parameters and assessment of tolerability by recording of adverse events. RESULTS: In total, 72 individuals entered the study. They were predominantly men (72.2%), with a mean (SD) age of 31.4 (8.26) years and a BMI of 25.8 (2.45) kg/m(2). The LS mean (SE) excreted urinary phosphorus was 16.8 (0.48) mmol/d during administration of LC tablets (±20% = ±3.35 mmol/d). The corresponding value during administration of LC oral powder was 15.2 (0.48) mmol/d; 90% CI for the difference between formulations was -2.38 to -0.82 mmol/d, confirming pharmacodynamic equivalence. The most common adverse events were gastrointestinal, and no serious adverse events were recorded. CONCLUSIONS: In this multiple-dose study, the oral powder and tablet formulations of LC were well tolerated and met the regulatory criteria for pharmacodynamic equivalence in these healthy volunteers. ClinicalTrials.gov identifier: NCT00880750.