Midazolam
Clinical Need
Ten percent of the U.S. population is expected to have seizures sometime in their lifetime, many requiring emergency interventions, according to epidemiological statistics. Prolonged or repetitive seizures can be life-threatening and cause neurological damage, which makes the effectiveness of initial interventions particularly important. Intravenously administered lorazepam or diazepam currently is standard care, but many circumstances and conditions make it difficult for paramedics to administer IV drugs. Rectal diazepam gel is the only drug approved for treating acute repetitive seizures in children outside a hospital setting.
Product Benefit
ITI’s midazolam spray is initially being developed for the treatment of acute repetitive seizures. We believe that our product is an excellent choice for seizure because of its anticonvulsant properties and emergency-ready attributes, i.e. rapid onset of action, ease of administration, and short duration. It could be self administered by patients and used by caregivers at home, emergency management staff prior to transporting patients to the hospital, and medical professionals in an emergency room.
Development Status
ITI has conducted three clinical studies in healthy volunteers. One study compared 5 mg of midazolam by intravenous (IV), intramuscular (IM) and intranasal routes of administration. Findings demonstrated that the intranasal dose was absorbed very rapidly and had 73% bioavailability; that its sedative effects were more similar to IV than to IM administration; and that it demonstrated rapid onset and short duration of action, ideal for seizure treatment.
A second Phase I clinical study investigated the pharmacokinetics and pharmacodynamics of the product. This study demonstrated similar peak time of effects, duration and plasma concentrations between intravenous and intranasal doses. As in the earlier clinical trial, intranasal midazolam appeared to be safe and well-tolerated by subjects.
A recent clinical program studied the pharmacokinetic and pharmacodynamic properties of a range of intranasally administered dose levels in patients on stable regimes of anti-epileptic drugs.
ITI Publications
Wermeling DP, Record KA, Kelly TH, Archer SM, Clinch T, Rudy AC. Pharmacokinetics and pharmacodynamics of a new intranasal midazolam folmulation in healthly volunteers. Anesth Analg 2006; 103:344-349.
Rudy AC, Record KE, Archer SM, Wermeling DP. Bioavailability and pharmacokinetics of intranasal midazolam. Presented at 2002 AAPS Annual Meeting. AAPS PharmSci 2002;4(4). Abstract W4175.
