Staccato Loxapine in Migraine (in Clinic)

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

The objective of this trial is to assess the efficacy and safety of Staccato Loxapine in patients with migraine headache with or without aura in a clinical setting.

This study will enroll male and female patients with migraine headache with or without aura. The study will randomize ~160 patients, 1:1:1:1 to receive one of the following treatments: 1.25 mg Staccato Loxapine; 2.5 mg Staccato Loxapine; 5 mg Staccato Loxapine; Staccato Placebo.

Inclusion Criteria:

1. Male and female patients between the ages of 18 to 65 years, inclusive.
2. Patients who have migraine headache with or without aura (diagnosis according to International Headache Society guidelines) for at least 6 months.
3. Patients who have a history of migraine and have had at least 3 migraine attacks in the last 3 month period (but not more than 8 migraine attacks in the last month).
4. Patients who have been pain free for at least 48 hours since the end of their last migraine attack.
5. Patients who have not taken any acute migraine or pain medication within 48 hours prior to dosing (including OTC products).
6. Patients who have a pain rating of Moderate or Severe (on a None-Mild- Moderate-Severe Scale) prior to dosing.
7. Patients who speak, read, and understand English and are willing and able to provide written informed consent on an IRB approved form prior to the initiation of any study procedures.
8. Patients who are willing and able to comply with the study schedule and requirements, are willing and able to travel to the Clinical Research Unit (CRU) for treatment and stay at the CRU for approximately a 4-6 hour period, and agree to return to the clinic within 5 working days of use of the investigational treatment.
9. Patients who are in good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, urinalysis, and in the opinion of the Principal Investigator.
10. Female participants (if of child-bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method throughout the study and for one week following the end of the study. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include 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 include: the rhythm method, withdrawal, condoms alone, or diaphragm alone.

Exclusion Criteria:

1. Patients who are currently taking antipsychotics, tricyclic antidepressants, valproate, barbiturates, benzodiazepines, or lithium must be excluded.
2. Patients with a history of contraindications to anticholinergics (bowel obstruction, urinary retention, acute glaucoma) must be excluded.
3. Patients with a history of allergy or intolerance to dibenzoxazepines (loxapine and amoxapine) must be excluded.
4. Patients with a history of extra-pyramidal disorders, movement disorders including Parkinson's disease, and patients with a history of neuroleptic malignant syndrome must be excluded.
5. Female patients who have a positive pregnancy test at screening or during randomization visit, or are breastfeeding must be excluded.
6. Patients who have a history within the past year of drug or alcohol dependence or abuse as defined by DSM-4 must be excluded.
7. Patients who have a history of syncope, unstable angina, myocardial infarction (within 6 months), congestive heart failure, transient ischemic attack, or pheochromocytoma must be excluded.
8. Patients who have a history of a major neurological disorder other than migraine (seizure disorder, subarachnoid bleeding, stroke, brain tumor) must be excluded.
9. Patients who have any other disease(s), by history, physical examination, or laboratory abnormalities (ALT or AST > 2-fold the upper limit of normal, Bilirubin > 1.5 mg/dL, or creatinine > 1.8 mg/dL) or that in the investigator's opinion, would present undue risk to the patient or may confound the interpretation of study results must be excluded.
10. Patients who have a history of asthma or chronic obstructive lung disease should be excluded.
11. Patients who have received an investigational drug within 30 days prior to the Screening Visit must be excluded.
12. Patients who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving loxapine, or unable to use the inhalation device, must be excluded.