Abstracts

Rationale: Lyrica (pregabalin) is an alpha-2-delta (A2D) ligand, approved in more than 120 countries including indications for neuropathic pain (NeP) associated with diabetic peripheral neuropathy, postherpetic neuralgia (PHN) or spinal cord injury, for fibromyalgia (FM), and adjunctive therapy for partial onset seizures (POS) in the US; peripheral and central (NeP), generalized anxiety disorder, and adjunctive therapy for POS in the EU; NeP and FM in Japan and PHN in China. The dose range for pregabalin as adjunctive therapy for POS in adults is 150 to 600 mg/day two or three times daily. Greater than 25,000 subjects have been exposed to pregabalin in clinical trials; approximately 15% from epilepsy studies. Since initial approval, the estimated cumulative post-marketing exposure to pregabalin exceeds 28 million patient-years. A clinical program in pediatric epilepsy is ongoing to potentially extend the adult indication to the pediatric population and to fulfill regulatory commitments.Methods: The pediatric epilepsy program is comprised of 6 multicenter studies and includes: a completed pharmacokinetic (PK), safety/tolerability study; 2 ongoing safety and efficacy studies to evaluate the efficacy and safety of pregabalin for the adjunctive treatment of partial onset seizures, one 12-week diary based study in children 4 to 16 years of age and one 2-week vEEG study in children age 1 month to 3 years; one 12-week diary based study in children and adults age 5 to 65 years to investigate the efficacy and safety of pregabalin for the adjunctive treatment of Primary Generalized Tonic Clonic seizures; 1 completed 1 year safety study for children who participated in the PK/safety/tolerability study and; a second ongoing 1 year safety trial for those patients who participated in the efficacy and safety trials.Results: Sixty five children across 4 age cohorts; 1-23 months, 2 - 6 years, 7 - 11 years, 12 - 16 years participated in the placebo controlled, parallel group, escalating dose, multiple dose PK safety/tolerability trial. Pregabalin at doses up to 10 mg/kg/day in children aged 1 month to 16 years and at doses up to 15 mg/kg/day in those < 6 years demonstrated acceptable safety and tolerability. For children weighing < 30 kg a 40% increase of body weight adjusted pregabalin daily dose (mg/kg/day) is required to achieve comparable exposure to children ≥ 30 kg or adults. Fifty four patients were enrolled in the completed long-term safety study; 29 subjects (53.7%) completed 12 months of pregabalin treatment. Long-term safety and tolerability evaluations indicate that pregabalin at doses up to and including 15 mg/kg/day appeared to be safe and well-tolerated in pediatric subjects 3 months through 16 years of age with partial onset seizures.Conclusions: An extensive global pregabalin development program in pediatric epilepsy in children 1 month and older is underway. Data in pediatric patients to date indicates that pregabalin is well tolerated with predictable pharmacokinetics.