Publications (3)11.15 Total impact
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Article: Assessment of pharmacodynamic equivalence and tolerability of lanthanum carbonate oral powder and tablet formulations: a single-center, randomized, open-label, 2-period crossover study in healthy subjects.
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ABSTRACT: 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. 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. 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. 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. 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.Clinical Therapeutics 05/2012; 34(6):1290-1300.e2. · 2.32 Impact Factor -
Article: Comparison of dietary phosphate absorption after single doses of lanthanum carbonate and sevelamer carbonate in healthy volunteers: a balance study.
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ABSTRACT: Lanthanum carbonate and sevelamer carbonate are noncalcium phosphate binders used to treat hyperphosphatemia in patients with chronic kidney disease. This is the first study to compare phosphate absorption from a standardized meal ingested with a typical clinical dose of these binders. Randomized open-label crossover study. Healthy volunteers were confined to a clinical research center during 4 study periods. Of 31 volunteers randomly assigned, 19 completed all treatments and 18 were analyzed in the pharmacodynamic set (1 was excluded because of vomiting). Participants were assigned in random order to meal alone, meal plus lanthanum carbonate (1 tablet containing 1,000 mg of elemental lanthanum), and meal plus sevelamer carbonate (three 800-mg tablets). The gastrointestinal tract was cleared, the meal was ingested (± treatment), and rectal effluent was collected. In a fourth period, volunteers repeated the study procedures while fasting. The primary end point, net phosphate absorption, was analyzed using a mixed-effect linear model. Phosphorus content of effluent and duplicate meal samples were measured using inductively coupled plasma-optical emission spectroscopy. The standard meal contained ∼375 mg of phosphate, 75% of which was absorbed (net absorption, 281.7 ± 14.1 mg [adjusted mean ± standard error]). Lanthanum carbonate decreased net phosphate absorption by 45% (net absorption, 156.0 ± 14.2 mg) compared with 21% (net absorption, 221.8 ± 14.1 mg) for sevelamer carbonate (P < 0.001). Lanthanum carbonate bound 135.1 ± 12.3 mg of phosphate, whereas sevelamer carbonate bound 63.2 ± 12.3 mg, a 71.9-mg difference (95% CI, 40.0-103.8; P < 0.001). Per tablet, this equates to 135 mg of phosphate bound with lanthanum carbonate versus 21 mg with sevelamer carbonate. A single-dose study. In healthy volunteers, 1,000 mg of lanthanum carbonate decreased phosphate absorption by 45% compared with a 21% decrease with 2,400 mg of sevelamer carbonate.American Journal of Kidney Diseases 02/2011; 57(5):700-6. · 5.43 Impact Factor -
Article: The effect of sevelamer carbonate and lanthanum carbonate on the pharmacokinetics of oral calcitriol.
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ABSTRACT: Lanthanum carbonate and sevelamer carbonate are non-calcium-based phosphate binders used to manage hyperphosphataemia in patients with chronic kidney disease (CKD). Patients with CKD may require intravenous or oral active vitamin D. We investigated the effects of lanthanum carbonate and sevelamer carbonate on the bioavailability of oral calcitriol. This was a three-period, crossover study in healthy volunteers. Forty-one individuals were randomized to one of six possible sequences, each consisting of three treatment periods separated by washouts. The treatments were calcitriol (1 μg at lunch), calcitriol with lanthanum carbonate (3000 mg/day) and calcitriol with sevelamer carbonate (7200 mg/day). Serum calcitriol levels were assessed at baseline and throughout the study. Co-administration of lanthanum carbonate with calcitriol had no significant effect on area under the curve over 48 h (AUC(0-48)) for serum exogenous calcitriol [least-squares (LS) mean, calcitriol with lanthanum carbonate vs calcitriol alone: 429 pg h/mL vs 318 pg h/mL, respectively; P = 0.171]. Similarly, there was no significant effect on maximum concentration (C(max)). In contrast, co-administration with sevelamer was associated with a significant reduction in bioavailability parameters for calcitriol (calcitriol with sevelamer carbonate vs calcitriol alone, LS mean AUC(0-48): 137 pg h/mL vs 318 pg h/mL, respectively; P = 0.024; LS mean C(max): 40.1 pg/mL vs 49.7 pg/mL, respectively; P < 0.001). Sevelamer carbonate significantly reduces serum concentrations of exogenous calcitriol when administered concomitantly with oral calcitriol, whereas lanthanum carbonate has no significant effect. This should be considered when treating CKD patients who require phosphate binders and oral vitamin D.Nephrology Dialysis Transplantation 10/2010; 26(5):1615-21. · 3.40 Impact Factor
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2011–2012
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Shire Plc
London, ENG, United Kingdom
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