Skip Over Navigation Links

Pre-Investigational New Drug Application Toxicity Studies of Nebulized Propofol Hemisuccinate

We are developing an inhaler system to treat intractable epilepsy and migraine. The system has two uses in epilepsy. In the first epilepsy application, the system is used by a patient experiencing a seizure aura to prevent a full-blown (motor) seizure. In the second epilepsy application, the system is used by a caregiver or by a bystander to treat a patient with epilepsy who is experiencing status epilepticus or seizure clusters in an out-of-hospital setting. The system may also be used to treat migraine: a patient experiencing a migraine aura or early migraine attack will use the system to abort the migraine symptoms and prevent the development of a full-blown headache.

The system administers a proprietary water-soluble prodrug form of propofol by nebulization into the deep lung. We have conducted extensive proof-of-principle studies demonstrating that intrapulmonary PHS effectively protects against seizures in animal models. We have also acquired preliminary data in an animal model of cortical spreading depression supporting the use of PHS in the treatment of migraine. Finally, we have shown that intrapulmonary PHS does not cause pulmonary damage or inflammation. We plan to conduct human safety and efficacy studies of nebulized PHS in normal volunteers and in persons with epilepsy who experience seizure auras prior to a full-blown motor seizure. In these early clinical trials, PHS solution will be administered with an off-the-shelf nebulizer system. At a later stage in this project, we anticipate developing a custom-designed miniaturized portable electronic nebulizer system that can easily be carried by patients. Following the development of the portable delivery system, we may conduct studies in the treatment of status epilepticus or seizure clusters or migraine.

Key Investigator

Regents of the University of California
Michael Rogawski, M.D.

Public Health Impact

Epilepsy and migraine are neurological disorders whose therapeutic approach is commonly preventive; treatment of acute attacks is difficult and frequently dependent on the assistance by a health-care professional. The proposed research seeks to develop a portable drug inhaler that can be used to stop a developing seizure or a migraine headache.

Outcomes

Approved studies are ongoing.

Project Details

  • Synthesis of GMP material
  • Formulation development
  • PK/ADME studies
  • IND-directed toxicology

Contact

Tony Jackson