Staccato Prochlorperazine in Migraine (Out Patient)

Study Overview
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Brief Summary
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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.

Official Title
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A Multi-center, Randomized, Double-Blind, Placebo-Controlled, Single Dose, Efficacy and Safety Outpatient Study of StaccatoTM Prochlorperazine for Inhalation in Patients With Migraine Headache

Conditions
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Migraine Headache, Aura

Intervention / Treatment
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* Drug: Inhaled Placebo
* Drug: Inhaled PCZ 5 mg
* Drug: Inhaled PCZ 7.5 mg
* Drug: Inhaled PCZ 10 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients between the ages of 18 to 70 years, inclusive. Patients who have migraine headache with or without aura (diagnosis according to International Headache Society guidelines) for at least 6 months. 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. 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. 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. 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. 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. 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: Patients who are currently taking tricyclic antidepressants, valproate, divalproex, barbitals, thiazolidinediones, phenothiazines, benzodiazepines, lithium or any hepatic toxic drugs must be excluded. Patients who are currently taking medications that prolong the QT/QTc interval (see Appendix 4) must be excluded. Patients with a history of contraindications to anticholinergics (bowel obstruction, urinary retention, acute glaucoma) must be excluded. Patients with a history of allergy or intolerance to phenothiazines and related drugs (prochlorperazine, chlorpromazine, promethazine, mesoridazine, thioridazine, fluphenazine, perphenazine) must be excluded. Patients with a history of extra-pyramidal disorders, movement disorders, neuroleptic malignant syndrome, or major affective disorder must be excluded. Female patients who have a positive pregnancy test at screening or are breastfeeding must be excluded. Patients who have a history within the past year of drug or alcohol dependence or abuse as defined by DSM-4 must be excluded. Patients who have a history of pheochromocytoma, seizure disorder or Parkinson's disease must be excluded. Patients who have a history of syncope, unstable angina, myocardial infarction (within 6 mos), congestive heart failure, or transient ischemic attack must be excluded. Patients who have a history of a major neurological disorder other than migraine (subarachnoidal bleeding, stroke, brain tumor) must be excluded. 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. Patients who have a history of asthma or chronic obstructive lung disease should be excluded. Patients who have received an investigational drug within 30 days prior to the Screening Visit must be excluded. 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. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Inhaled Placebo<br>Inhaled Staccato Placebo | Drug: Inhaled Placebo<br>* Inhaled Staccato Placebo<br>|
| Experimental: Inhaled PCZ 5 mg<br>Inhaled Staccato Prochlorperazine 5 mg | Drug: Inhaled PCZ 5 mg<br>* Inhaled Staccato Prochlorperazine 5 mg<br>|
| Experimental: Inhaled PCZ 7.5 mg<br>Inhaled Staccato Prochlorperazine 7.5 mg | Drug: Inhaled PCZ 7.5 mg<br>* Inhaled Staccato Prochlorperazine 7.5 mg<br>|
| Experimental: Inhaled PCZ 10 mg<br>Inhaled Staccato Prochlorperazine 10 mg | Drug: Inhaled PCZ 10 mg<br>* Inhaled Staccato Prochlorperazine 10 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Headache Pain Relief at 2 hr | Headache pain relief at 2 hr post-dose by IHS Definition (none=0 or mild=1), | 2 hr post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responders, Pain-Free at 2 Hours | Percentage of Responders, Pain-Free, by Treatment Group over Time | 2 hours | 
| Survival of Headache Pain Relief | Survival for time to the first successful headache pain relief by Pain-IHS definition over the 0 to 4 hr period by treatment assigned. Pairwise comparisons were made for each of the 3 active doses to placebo. Survival Analysis (Kaplan-Meyer) was included to evaluate treatment efficacy over the 0 to 4 hr period. All tests were 2-sided with a p-value at α=0.05. | 0 to 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine, Staccato Prochlorperazine, Migraine headache with or without aura.