Staccato Prochlorperazine in Migraine (Out Patient)
Condition: Migraine Headache; Aura
MeSH terms: Migraine Disorders; Headache
Intervention: Inhaled Placebo; Inhaled PCZ 5 mg; Inhaled PCZ 7.5 mg; Inhaled PCZ 10 mg
Intervention description: Inhaled Staccato Placebo; Inhaled Staccato Prochlorperazine 5 mg; Inhaled Staccato Prochlorperazine 7.5 mg; Inhaled Staccato Prochlorperazine 10 mg
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 400.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Migraine, Staccato Prochlorperazine; Migraine headache with or without aura.

Summary:

      Staccato Prochlorperazine is being developed to treat patients suffering from acute migraine
      headaches. In October 2005, we completed a 75 patient, multi-center, double-blind
      placebo-controlled Phase 2A clinical trial in patients suffering from moderate to severe
      acute migraine headaches. This Phase 2B clinical trial of Staccato Prochlorperazine has been
      initiated to assess the efficacy and safety in outpatients with migraine headache with or
      without aura.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male and female patients between the ages of 18 to 70 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 per month). Current and
             past migraine medication history must be recorded.

          4. Patients who agree to: not use the study drug within 72 hr of a prior migraine attack,
             and to use the investigational medication when they have a pain rating of Moderate or
             Severe (on a None, Mild, Moderate or Severe Scale) prior to dosing.

          5. Patients who speak, read, and understand English sufficiently well and are willing and
             able to provide written informed consent on an IRB approved form prior to the
             initiation of any study procedures.

          6. Patients who are willing and able comply with the study schedule and study
             requirements, and agree to return to the clinic within 5 working days of use of the
             investigational treatment.

          7. 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.

          8. 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 tricyclic antidepressants, valproate, divalproex,
             barbitals, thiazolidinediones, phenothiazines, benzodiazepines, lithium or any hepatic
             toxic drugs must be excluded.

          2. Patients who are currently taking medications that prolong the QT/QTc interval (see
             Appendix 4) must be excluded.

          3. Patients with a history of contraindications to anticholinergics (bowel obstruction,
             urinary retention, acute glaucoma) must be excluded.

          4. Patients with a history of allergy or intolerance to phenothiazines and related drugs
             (prochlorperazine, chlorpromazine, promethazine, mesoridazine, thioridazine,
             fluphenazine, perphenazine) must be excluded.

          5. Patients with a history of extra-pyramidal disorders, movement disorders, neuroleptic
             malignant syndrome, or major affective disorder must be excluded.

          6. Female patients who have a positive pregnancy test at screening or are breastfeeding
             must be excluded.

          7. Patients who have a history within the past year of drug or alcohol dependence or
             abuse as defined by DSM-4 must be excluded.

          8. Patients who have a history of pheochromocytoma, seizure disorder or Parkinson's
             disease must be excluded.

          9. Patients who have a history of syncope, unstable angina, myocardial infarction (within
             6 mos), congestive heart failure, or transient ischemic attack must be excluded.

         10. Patients who have a history of a major neurological disorder other than migraine
             (subarachnoidal bleeding, stroke, brain tumor) must be excluded.

         11. 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.

         12. Patients who have a history of asthma or chronic obstructive lung disease should be
             excluded.

         13. Patients who have received an investigational drug within 30 days prior to the
             Screening Visit must be excluded.

         14. Patients who have a history of risk factors for Torsade de Pointes (e.g., heart
             failure, hypokalemia, family history of Long QT Syndrome) must be excluded.

         15. Patients who have a marked prolongation of QT/QTc interval (e.g., demonstration of a
             QT interval >450 ms on screening ECG) must be excluded.

         16. Patients who are considered by the investigator, for any reason, to be an unsuitable
             candidate for receiving prochlorperazine, or unable to use the inhalation device, must
             be excluded.