UCB today announced findings from new studies of the once-daily antiepileptic drug (AED) Keppra XR™ (levetiracetam) extended-release tablets comparing tolerability vs. levetiracetam immediate release and reporting on additional dosing schedules. The data were among five studies that were presented at the 62nd annual meeting of the American Epilepsy Society in Seattle.
Keppra XR was approved by the U.S. Food and Drug Administration in September 2008 for use as adjunctive treatment for people with partial-onset seizures who are 16 years of age and older.
"In this new meta-analysis, patients taking Keppra XR experienced fewer nervous system side effects than those taking the same dose of twice daily levetiracetam," said James Zackheim, Medical Director, CNS, UCB. "Keppra XR is the only once-daily, extended-release formulation of levetiracetam, and there is no generic alternative available."
Summary of Keppra XR Data Presented at 2008 AES Annual Meeting
Safety Profile of Levetiracetam Extended Release Compared to Immediate Release: An Indirect Comparison Using a Meta-Analytic Approach
Researchers conducted a meta-analysis of Phase III data to determine whether Keppra XR is associated with any tolerability advantages versus the same daily dose of levetiracetam IR. According to the meta-analysis, patients taking Keppra XR once-daily had lower rates of some adverse events versus levetiracetam IR twice-daily.
- In terms of overall tolerability, 52.8% of Keppra XR patients reported any adverse event, compared with 79% of patients taking levetiracetam IR.
- While adverse events associated with levetiracetam IR were also observed with Keppra XR, patients treated with Keppra XR once-daily experienced statistically significantly lower rates of adverse events related to nervous system disorders (i.e., headache, somnolence and dizziness) versus levetiracetam IR twice-daily.
- Keppra XR-treated patients reported numerically lower rates of psychiatric disorders (i.e., nervousness, anxiety and depression) and nutrition/metabolism disorders.
- No other differences in rates of adverse events were statistically significant.
Poster Session 3, Monday, December 8, 8:00 am – 1:30 pm (Abstract 3.243)Florent Richy, MPH, PhD, Soutrik Banerjee, MD, PhD, Christophe Gervasoni, MS, Patricia Grossman, PharmD, MBA, Sandra Helmers, MDUCB Pharma, Inc.; University of Liège, Belgium; Joseph Fourier University, France; Stendhal University, France; Emory University Hospital, USA
Single Dose Bioequivalence between Levetiracetam 2 x 750 mg XR Tablets and 3 x 500 mg XR Tablets and Food Effect on 2 x 750 mg XR Tablets in Healthy Subjects
This study demonstrated that an investigational 750 mg tablet strength of Keppra XR is bioequivalent to the approved 500 mg tablet when these are each combined to achieve a 1,500 mg dose. Results show that a single dose of 2 x 750 mg Keppra XR tablets was bioequivalent to a 3 x 500 mg single dose of Keppra XR in healthy adults, and that food intake did not significantly modify Keppra XR 2 x 750 mg disposition.
- The median time to peak plasma concentration was approximately 4 to 5 hours for each dose.
- Each dose resulted in a similar half-life (the time required for half the quantity of a drug in the body to be metabolized or eliminated), apparent total clearance (the rate at which a drug in the body is metabolized or eliminated), and apparent total distribution (the amount of fluid that would be required to dissolve the total amount of drug needed to achieve the same concentration as that found in the blood).
- When the 2 x 750 mg Keppra XR dose was taken with food, the time to peak concentration was increased by 2 hours relative to fasted intake, while Cmax (the peak concentration of a drug in the body) remained within bioequivalence limits.
- For all three Keppra XR dosing schedules (3 x 500 mg, 2 x 750 fasted and 2 x 750 fed), tolerability was good and the rates of trea™ent-emergent adverse events were similar across all groups; in addition, adverse events were virtually all mild, and all resolved by the end of the study.
Poster Session 3, Monday, December 8, 8:00 am – 1:30 pm (Abstract 3.239)Christian Otoul, Elisabeth Rouits, Ingrid Burton, Evelyne Guénolé, Mona Troenaru, Ans Valgaeren, Pierre Boulanger, Maria Laura Sargentini-MaierUCB Pharma SA, Braine-L'Alleud, Belgium; Depar™ent of Pharmacokinetics, SGS Life Science Services, Wavre, Belgium; Therapharm Recherches, Caen, France
Additional Keppra XR Data Presented at 2008 AES Annual Meeting:
- Population Pharmacokinetics of Levetiracetam Extended-Release 500 mg Tablets
Poster Session 3, Monday, December 8, 8:00 am – 1:30 pm (Abstract 3.247)Elisabeth Rouits, M. Lovern, Maria Laura Sargentini-Maier and Armel StockisUCB Pharma, Braine-l'Alleud, Belgium
- Population Dose–Response Modeling of Levetiracetam Extended- and Immediate-Release Formulations in Adults with Partial-Onset Seizures
Poster Session 3, Monday, December 8, 8:00 am – 1:30 pm (Abstract 3.25)Rik Schoemaker, Eric Snoeck, Armel Stockis, Christian Otoul, Maria Laura Sargentini-MaierExprimo NV, Mechelen, Belgium; Pharmacometrics Depar™ent, UCB Pharma SA, Braine-l'Alleud, Belgium
- Dose-Proportionality of Levetiracetam 500 mg Extended-Release Tablets from 1 g to 3 g Once Daily
Poster Session 3, Monday, December 8, 8:00 am – 1:30 (Abstract 3.263)Ans Valgaeren, Nathalie Toublanc, Ingrid Burton, Sandrine Gelu-Mantoulet, Mona Troenaru, Christian Otoul, Maria Laura Sargentini-Maier, Armel StockisUCB Pharma SA, Braine-L'Alleud, Belgium; Depar™ent of Pharmacokinetics, SGS Life Science Services, Wavre, Belgium; Therapharm Recherches, Caen, France
Keppra XR cannot be substituted with any IR levetiracetam or any other antiepileptic medication at the pharmacy counter without a physician's approval.
Source: UCB Group