Treatment of Induced Panic Attack
Conditions
Keywords
Staccato™ Alprazolam, Panic Attack, Inhaled alprazolam
Brief summary
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
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.
Interventions
DRUGInhaled placebo
Inhaled Staccato Alprazolam Placebo
Inhaled Staccato Alprazolam 1 mg
Inhaled Staccato Alprazolam 2 mg
DRUGIV doxapram
0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo
Sponsors
Alexza Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Doxapram-induced Panic Attack | 0 to 2 hours | doxapram-induced panic attack of sufficient intensity (DIPASI) defined as a 10 or greater increase from baseline in the acute panic inventory (API) |
| Duration of the Doxapram-induced Panic Attack | 1 hr post-dose | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Borg Max Change From Baseline | 45 minutes | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RCT Placebo Subjects received inhaled placebo after 0.5 mg/kg doxapram IV in the randomized controlled trial
Inhaled placebo: Inhaled Staccato Alprazolam Placebo
IV doxapram: 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo | 20 |
| 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
Inhaled alprazolam 1 mg: Inhaled Staccato Alprazolam 1 mg
IV doxapram: 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo | 20 |
| 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
Inhaled alprazolam 1 mg: Inhaled Staccato Alprazolam 1 mg
IV doxapram: 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo | 7 |
| 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
Inhaled alprazolam 2 mg: Inhaled Staccato Alprazolam 2 mg
IV doxapram: 0.5 mg/kg doxapram IV approximately 10s after receiving inhaled alprazolam or placebo | 2 |
| Total | 49 |
Baseline characteristics
| Characteristic | RCT Alprazolam 1 mg | Open Label Inhaled Alprazolam 1 mg | RCT Placebo | Initial Inhaled Alprazolam 2 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 7 Participants | 20 Participants | 2 Participants | 49 Participants |
| Age, Continuous | 32.1 years STANDARD_DEVIATION 9.45 | 43.1 years STANDARD_DEVIATION 13.6 | 33.2 years STANDARD_DEVIATION 10.2 | 37.5 years STANDARD_DEVIATION 0.707 | 34.3 years STANDARD_DEVIATION 10.66 |
| Region of Enrollment United States | 20 Participants | 7 Participants | 20 Participants | 2 Participants | 49 Participants |
| Sex: Female, Male Female | 12 Participants | 1 Participants | 9 Participants | 1 Participants | 23 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 11 Participants | 1 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 7 | 0 / 2 |
| other Total, other adverse events | 2 / 20 | 11 / 20 | 1 / 7 | 1 / 2 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 7 | 0 / 2 |
Outcome results
Primary
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)
Time frame: 1 hr post-dose
Population: RCT Population (N=40)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RCT Placebo | Duration of the Doxapram-induced Panic Attack | 12.2 minutes | Standard Deviation 17.2 |
| RCT Alprazolam 1 mg | Duration of the Doxapram-induced Panic Attack | 9.25 minutes | Standard Deviation 14.1 |
p-value: 0.368Wilcoxon (Mann-Whitney)
Primary
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)
Time frame: 0 to 2 hours
Population: RCT Population (N=40)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| RCT Placebo | Number of Participants With Doxapram-induced Panic Attack | 14 Participants |
| RCT Alprazolam 1 mg | Number of Participants With Doxapram-induced Panic Attack | 9 Participants |
p-value: 0.2Fisher Exact
Secondary
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
Time frame: 45 minutes
Population: RCT Population (N=40)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RCT Placebo | Borg Max Change From Baseline | 5.73 units on a scale | Standard Deviation 2.85 |
| RCT Alprazolam 1 mg | Borg Max Change From Baseline | 4.63 units on a scale | Standard Deviation 2.56 |
p-value: 0.207t-test, 2 sided