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Pharmacokinetics of Lacosamide and Omeprazole Coadministration in Healthy Volunteers: Results from a Phase I, Randomized, Crossover Trial

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Abstract

Background

The antiepileptic drug lacosamide has a low potential for drug–drug interactions, but is a substrate and moderate inhibitor of the cytochrome P450 (CYP) enzyme CYP2C19.

Objective

This phase I, randomized, open-label, two-way crossover trial evaluated the pharmacokinetic effects of lacosamide and omeprazole coadministration.

Methods

Healthy, White, male volunteers (n = 36) who were not poor metabolizers of CYP2C19 were randomized to treatment A (single-dose 40 mg omeprazole on days 1 and 8 together with 6 days of multiple-dose lacosamide [200–600 mg/day] on days 3–8) and treatment B (single doses of 300 mg lacosamide on days 1 and 8 with 7 days of 40 mg/day omeprazole on days 3–9) in pseudorandom order, separated by a ≥7-day washout period. Area under the concentration–time curve (AUC) and peak concentration (C max) were the primary pharmacokinetic parameters measured for lacosamide or omeprazole administered alone (reference) or in combination (test). Bioequivalence was determined if the 90  % confidence interval (CI) of the ratio (test/reference) fell within the acceptance range of 0.8–1.25.

Results

The point estimates (90 % CI) of the ratio of omeprazole + lacosamide coadministered versus omeprazole alone for AUC (1.098 [0.996–1.209]) and C max (1.105 [0.979–1.247]) fell within the acceptance range for bioequivalence. The point estimates (90 % CI) of the ratio of lacosamide + omeprazole coadministration versus lacosamide alone also fell within the acceptance range for bioequivalence (AUC 1.133 [1.102–1.165]); C max 0.996 (0.947–1.047).

Conclusion

Steady-state lacosamide did not influence omeprazole single-dose pharmacokinetics, and multiple-dose omeprazole did not influence lacosamide single-dose pharmacokinetics.

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Acknowledgments

The authors thank Pharm PlanNet Contract Research GmbH (Mönchengladbach, Germany) for performing the clinical part of the trial, in accordance with the current laws of Germany, and Independent Clinical Research Consulting (Berlin, Germany) for data management. We further thank IKP Bobenheim (Grünstadt, Germany) for the analytical work on both lacosamide and omeprazole samples and Medizinische Laboratorien Marienhof GmbH (Mönchengladbach, Germany) for the safety laboratory analyses. Biostatistical analysis was performed by the CRO M.A.R.C.O. Institute for Clinical Research and Statistics—Dr. Wargenau (Düsseldorf, Germany) under the supervision of UCB Pharma. UCB Pharma was responsible for clinical trial supply management and also helped supervise the clinical trial. Merrilee Johnstone, PhD, from Prescott Medical Communications Group (Chicago, IL, USA) provided writing assistance. Editorial support was provided by Karen Burrows of Evidence Scientific Solutions (Horsham, UK), which was funded by UCB Pharma.

Financial Disclosure

UCB Pharma (Monheim, Germany) provided the trial supplies and sponsored and funded the trial. The authors are employees of UCB Biosciences GmbH (part of UCB Pharma).

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Authors and Affiliations

  1. UCB Biosciences GmbH, UCB Pharma, Global Statistical Sciences, Alfred-Nobel-Str. 10, 40789, Monheim am Rhein, Germany

    Willi Cawello, Christa Mueller-Voessing & Andreas Fichtner

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  1. Willi Cawello
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  2. Christa Mueller-Voessing
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  3. Andreas Fichtner
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Correspondence to Willi Cawello.

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Cawello, W., Mueller-Voessing, C. & Fichtner, A. Pharmacokinetics of Lacosamide and Omeprazole Coadministration in Healthy Volunteers: Results from a Phase I, Randomized, Crossover Trial. Clin Drug Investig 34, 317–325 (2014). https://doi.org/10.1007/s40261-014-0177-2

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