Abstract
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/m2. 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.
Key words
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Article info
Publication history
Published online: June 04, 2012
Accepted:
May 10,
2012
Identification
Copyright
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
