Staccato Alprazolam in Panic Attack

Study Overview
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Brief Summary
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We are developing Staccato™ Alprazolam for the treatment of Panic attacks associated with panic disorder. This study will provide an initial assessment of efficacy, and to continue to describe the tolerability and pharmacokinetics, of a single inhaled dose of Staccato Alprazolam on a doxapram-induced panic attack in patients with panic disorder.

Detailed Description
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The study will be conducted at multiple centers. A total of 42 male and female panic disorder patients will be studied. The first 6 subjects will receive Staccato Alprazolam 1 mg open label to validate the dose selection. The remaining 36 subjects will be treated with either Staccato Alprazolam at the chosen dose; or with Staccato Placebo in a double blind, randomized order.

Official Title
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Investigation of a Single Dose of Staccato™ Alprazolam for Inhalation on Doxapram-Induced Panic Attack in Patients With Panic Disorder

Conditions
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Treatment of Induced Panic Attack

Intervention / Treatment
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* Drug: Inhaled placebo
* Drug: Inhaled alprazolam 1 mg
* Drug: Inhaled alprazolam 2 mg
* Drug: IV doxapram


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who meet DSM-IV criteria for panic disorder, with or without agoraphobia. Subjects who have had at least one panic attack per week in each of the four weeks prior to the start of treatment and/or have a Mobility Inventory Score of 3.3 (alone) or 2.5 (accompanied). Male or female subjects who are English-speaking between 18 and 55 years of age. Female subjects who are not pregnant, or are surgically sterile or 2 years postmenopausal. If of childbearing potential, she must be using a medically-accepted method of birth control and agree to continue use of this method for at least 30 days after the study (i.e., barrier method with spermicide, steroidal contraceptive [oral, transdermal, and implanted, including Depo-Provera; contraceptives must be used in conjunction with a barrier method], or intrauterine device). Subjects who are medically healthy (i.e. without a clinically significant unstable medical condition such as asthma, coronary artery disease, renal insufficiency, etc.) Subjects who are able to give informed consent for participation. Subjects who are able to be withdrawn from current panic disorder medication because it is ineffective. Exclusion Criteria: Subjects who have met DSM-IV criteria for substance abuse or dependence within six months of study entry must be excluded. Subjects with a baseline Acute Panic Inventory (22 item test) score of 41 or higher on the test day must be excluded. Subjects who are taking benzodiazepines, SSRIs, or medication that is effective for the prevention or treatment of the patient's panic disorder (i.e., no patient will be withdrawn for medication that is working for the purpose of entry into this study) must be excluded. Subjects who are clinically depressed must be excluded. Subjects who have received an investigational drug within 30 days (or within 5 half lives of the investigational drug) prior to test day must be excluded. Subjects with epilepsy or other convulsive disorders must be excluded. Subjects with a history of allergy or intolerance to benzodiazepines or related drugs (alprazolam, lorazepam, diazepam, etizolam, clonazepam, adinazolam) must be excluded. Subjects who test positive for alcohol or have a positive urine drug screen for illicit or disallowed drugs must be excluded. Subjects should refrain from consuming alcohol for at least 48 hours prior to dosing. Female subjects who are breastfeeding or have a positive pregnancy test must be excluded. Subjects who have any other disease or condition, by history, physical examination, or laboratory abnormalities that in the investigator's opinion, would present undue risk to the subject, or may confound the interpretation of study results must be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: RCT Placebo<br>Subjects received inhaled placebo after 0.5 mg/kg doxapram IV in the randomized controlled trial | Drug: Inhaled placebo<br>* Inhaled Staccato Alprazolam Placebo<br>Drug: IV doxapram<br>* 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo<br>|
| Experimental: RCT Alprazolam 1 mg<br>Subjects received 1 mg inhaled Staccato alprazolam 10 s after 0.5 mg/kg doxapram IV in the randomized controlled trial | Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato Alprazolam 1 mg<br>Drug: IV doxapram<br>* 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo<br>|
| Experimental: Open Label Inhaled Alprazolam 1 mg<br>Subjects received 1 mg inhaled Staccato alprazolam 10 s after 0.5 mg/kg doxapram IV in the open label dose validation | Drug: Inhaled alprazolam 1 mg<br>* Inhaled Staccato Alprazolam 1 mg<br>Drug: IV doxapram<br>* 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo<br>|
| Experimental: Initial Inhaled Alprazolam 2 mg<br>Subjects received 2 mg inhaled Staccato alprazolam 10 s after 0.5 mg/kg doxapram IV in the initial open label dose assessment | Drug: Inhaled alprazolam 2 mg<br>* Inhaled Staccato Alprazolam 2 mg<br>Drug: IV doxapram<br>* 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Doxapram-induced Panic Attack | doxapram-induced panic attack of sufficient intensity (DIPASI) defined as a 10 or greater increase from baseline in the acute panic inventory (API) | 0 to 2 hours | 
| Duration of the Doxapram-induced Panic Attack | Length of time from the doxapram injection to the time at which the acute panic inventory (API) value returns to within 10 points of the baseline API value. 0=never exceeded 0, 61=exceeded by more than 10 points still at end of assessment of 60 minutes. Thus each would have a duration whether or not they had a panic attack (DIPASI) | 1 hr post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Borg Max Change From Baseline | Subjects asked to Point to the number (0 to 10) which matches how breathless you feel now where 0=nothing at all to 10=very, very strong | 45 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Staccato™ Alprazolam, Panic Attack, Inhaled alprazolam