Staccato Loxapine in Migraine (Out Patient)

A Multi-center, Randomized, Double-Blind, Placebo-Controlled, Single Dose Efficacy and Safety Study of Staccato® Loxapine for Inhalation in Outpatients With Migraine Headache

Assess the safety and efficacy of Staccato Loxapine in patients with moderate to severe migraine headache with or without aura in an outpatient setting.

This study was designed to compare the safety and pharmacodynamic profiles of concomitant administration of single doses of ADASUVE and intramuscular (IM) lorazepam compared to that of each agent administered alone. Respiratory pharmacodynamics were monitored through recordings of respirations/minute and pulse oximetry. Other pharmacodynamic safety measures included effects on blood pressure, heart rate, sedation, and psychomotor measures of attention, information processing speed, reaction time, and coordination.

Inclusion Criteria

• Male or female between the ages of 18 to 65 years, inclusive
• History of migraine headache with or without aura (according to IHS Criteria 1.1 or 1.2 for diagnosis beginning at least 6 months prior to study entry) (International Headache Society Clinical Trials Subcommittee, 2000)
• At least 3 migraine attacks in the last 3 month period (but not more than 8 migraine attacks in the last month)
• Pain rating of moderate or severe (on a none-mild- moderate-severe scale) prior to dosing
• Agreed not to use the study drug within 72 hours of a prior migraine attack
• Agreed not to use any acute migraine or pain medication within 48 hours prior to dosing (including over-the-counter [OTC] products); medications for migraine prophylaxis other than those that were exclusionary were permitted if stable doses had been given for at least 30 days prior to screening
• Agreed not to use medications (including OTC products) for motion sickness, tinnitus, or vertigo within 48 hours prior to dosing.
• Were able to speak, read, and understand English and were willing and able to provide written informed consent on an IRB-approved form prior to the initiation of any study procedures
• Were willing and able to comply with the study schedule and requirements, and agreed to return to the clinic within 5 working days of use of the study drug
• In good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead electrocardiogram (ECG), blood chemistry profile, hematology, urinalysis, and in the opinion of the investigator
• Female participants (if of child-bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) who agreed to use a medically acceptable and effective birth control method throughout the study and for 1 week following the end of the study. Medically acceptable methods of contraception that could be used by the participant and/or his/her partner included abstinence, birth control pills or patches, diaphragm with spermicide, intrauterine device (IUD), condom with foam or spermicide, vaginal spermicidal suppository, surgical sterilization, and progestin implant or injection. Prohibited methods included the rhythm method, withdrawal, condoms alone, or diaphragm alone.

Exclusion Criteria

• Use of antipsychotics (including butryophenones, phenothiazines, thioxanthenes, aripiprazle, olanzapine, risperidone), tricyclic antidepressants, trazodone, anticonvulsants (except topiramate), barbiturates, benzodiazepines, or lithium within 14 days or 5 half-lives, whichever was longer, of randomization and at anytime throughout the study
• History of contraindications to anticholinergic agents (eg, bowel or urinary obstruction, stenosing peptic ulcers, narrow-angle glaucoma)
• History of allergy or intolerance to dibenzoxazepines (loxapine and amoxapine)
• History of extrapyramidal disorders, movement disorders including Parkinson's disease or neuroleptic malignant syndrome
• Female patients with a positive pregnancy test at screening or during randomization visit, or who were breastfeeding
• History within the past year of drug or alcohol dependence or abuse as defined by DSM IV
• History of syncope, unstable angina, myocardial infarction (within 6 months), congestive heart failure, or uncontrolled hypertension
• History of a major neurological disorder other than migraine (seizure disorder, subarachnoid bleeding, stroke, brain tumor, or transient ischemic attack)
• Any other disease(s), by history, physical examination, or laboratory abnormalities (including alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2-fold the upper limit of normal, total bilirubin > 1.5 mg/dL, or creatinine > 1.8 mg/dL), that in the investigator's opinion, would present undue risk to the patient or could confound the interpretation of study results
• History of asthma or chronic obstructive lung disease or any use of an inhaler prescribed for wheezing or bronchospasm in the past 5 years
• Receipt of an investigational drug within 30 days prior to the screening visit
• Considered by the investigator, for any reason, to be an unsuitable candidate for receiving loxapine, or unable to use the inhalation device