IV Topiramate

Topiramate (TPM) is a commonly prescribed antiepileptic drug (AED) which is also approved for prevention of migraine. Currently there are no options for patients on maintenance TPM therapy who are temporarily unable to take oral medications after hospital or emergency department (ED) admission. Captisol-enabled (CE) TPM was developed to enable intravenous (IV) or intramuscular administration of TPM. Two phase I clinical studies investigating the pharmacokinetics and safety of IV infusion of CE TPM in adult epilepsy or migraine patients and in volunteers have been completed in which IV TPM was shown to be well tolerated and to have rapid onset of action.

CURx has completed a licensing deal with Ligand Pharmaceuticals for development and commercialization of IV TPM. Orphan drug status has been granted by the FDA’s Office of Orphan Products Development. IV TPM is being developed in clinical trials as a replacement therapy for epilepsy patients on oral TPM maintenance therapy in hospital or the ED. Those benefiting from IV TPM approval will therefore include epilepsy patients who take TPM pills on a daily basis but who are unable to take oral medications due to scheduled surgical procedures, unscheduled hospitalizations or ED visits or gastrointestinal problems.

CURx has completed the Phase 1 Pivotal Trial for the first and only IV formulations of Anti-Epileptic Drug Topiramate. The results have been analyzed and we anticipate NDA submission to the FDA in the 4th Quarter of 2024 and marketing approval in the US in late 2025. The product uses Captisol (Cydex Pharma/ Ligand) to solubilize topiramate. Captisol has been successfully used to solubilize several products including products marketed by Merck, Pfizer and Gilead.

Publications

Intravenous topiramate: Safety and pharmacokinetics following a single dose in patients with epilepsy or migraines taking oral topiramate. Epilepsia 54; 1106–1111 (2013) Anne M. Clark, Robert L. Kriel, Ilo E. Leppik, James R. White, Thomas R. Henry, Richard C. Brundage and James C. Cloyd.

Intravenous topiramate: Comparison of pharmacokinetics and safety with the oral formulation in healthy volunteers. Epilepsia 54; 1099–1105 (2013) Anne M. Clark, Robert L. Kriel, Ilo E. Leppik, Susan E. Marino, Usha Mishra, Richard C. Brundage and James C. Cloyd.