Staccato Alprazolam in Panic Attack

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

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.

Study Overview

• Status: Completed
• Conditions: Treatment of Induced Panic Attack
• Intervention / Treatment: Drug: Inhaled placebo; Drug: IV doxapram; Drug: Inhaled alprazolam 1 mg; Drug: Inhaled alprazolam 2 mg

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Brooklyn, New York, United States, 11203-2056
      • SUNY Downstate Medical Center
    • New York, New York, United States, 10029
      • Mt. Sinai School of Medicine
    • New York, New York, United States, 10021
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects who meet DSM-IV criteria for panic disorder, with or without agoraphobia.
2. 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).
3. Male or female subjects who are English-speaking between 18 and 55 years of age.
4. 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).
5. Subjects who are medically healthy (i.e. without a clinically significant unstable medical condition such as asthma, coronary artery disease, renal insufficiency, etc.)
6. Subjects who are able to give informed consent for participation.
7. Subjects who are able to be withdrawn from current panic disorder medication because it is ineffective.

Exclusion Criteria:

1. Subjects who have met DSM-IV criteria for substance abuse or dependence within six months of study entry must be excluded.
2. Subjects with a baseline Acute Panic Inventory (22 item test) score of 41 or higher on the test day must be excluded.
3. 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.
4. Subjects who are clinically depressed must be excluded.
5. 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.
6. Subjects with epilepsy or other convulsive disorders must be excluded.
7. Subjects with a history of allergy or intolerance to benzodiazepines or related drugs (alprazolam, lorazepam, diazepam, etizolam, clonazepam, adinazolam) must be excluded.
8. 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.
9. Female subjects who are breastfeeding or have a positive pregnancy test must be excluded.
10. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: RCT Placebo; Subjects received inhaled placebo after 0.5 mg/kg doxapram IV in the randomized controlled trial	Drug: Inhaled placebo; Inhaled Staccato Alprazolam Placebo; Drug: IV doxapram; 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo
Experimental: RCT Alprazolam 1 mg; Subjects received 1 mg inhaled Staccato alprazolam 10 s after 0.5 mg/kg doxapram IV in the randomized controlled trial	Drug: IV doxapram; 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo; Drug: Inhaled alprazolam 1 mg; Inhaled Staccato Alprazolam 1 mg
Experimental: Open Label Inhaled Alprazolam 1 mg; Subjects received 1 mg inhaled Staccato alprazolam 10 s after 0.5 mg/kg doxapram IV in the open label dose validation	Drug: IV doxapram; 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo; Drug: Inhaled alprazolam 1 mg; Inhaled Staccato Alprazolam 1 mg
Experimental: Initial Inhaled Alprazolam 2 mg; Subjects received 2 mg inhaled Staccato alprazolam 10 s after 0.5 mg/kg doxapram IV in the initial open label dose assessment	Drug: IV doxapram; 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo; Drug: Inhaled alprazolam 2 mg; Inhaled Staccato Alprazolam 2 mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Alexza Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Sanjay Mathew, MD, Mt. Sinai School of Medicine; Principal Investigator: Jeremy Coplan, MD, State University of New York - Downstate Medical Center; Principal Investigator: Laszlo Papp, MD, New York State Psychiatric Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2007
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: May 22, 2007
• First Submitted That Met QC Criteria: May 22, 2007
• First Posted (Estimate): May 23, 2007

Study Record Updates

• Last Update Posted (Actual): June 16, 2017
• Last Update Submitted That Met QC Criteria: June 15, 2017
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: Staccato™ Alprazolam, Panic Attack, Inhaled alprazolam
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Panic Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Respiratory System Agents; Central Nervous System Stimulants; Alprazolam; Doxapram
• Other Study ID Numbers: AMDC-002-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No