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Phase 3 safety and efficacy study of Staccato Loxapine in the treatment of acute agitation in bipolar 1 disorder patients.
This is an in-clinic, multi-center, randomized, double-blind, placebo-controlled study of 2 dose levels of Staccato Loxapine, 5 and 10 mg. Patients may receive up to 3 doses of study drug in a 24-hour period, depending on their clinical status. The primary endpoint is the change from baseline in the PANSS (Positive and Negative Symptom Scale) Excited Component (also known as PEC) score, performed at 2 hours after the first dose.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Inhaled Placebo | Placebo Comparator | Inhaled Staccato Placebo, may repeat after 2 hours x 2 |
|
| Inhaled Loxapine 5 mg | Experimental | Inhaled Staccato Loxapine 5 mg, may repeat after 2 hours x 2 |
|
| Inhaled Loxapine 10 mg | Experimental | Inhaled Staccato Loxapine 10 mg, may repeat after 2 hours x 2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inhaled Placebo | Drug | Inhaled loxapine Placebo, may repeat after 2 hours x 2 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo | The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (min) to 7 (max). The PANSS-EC, the sum of these 5 subscales, thus ranges from 5 to 35. Individuals were eligible if they had a PANSS-EC of ≥14 (out of 35) and a score ≥4 (out of 7) on at least 1 of the 5 items. | Baseline and 2 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Global Impression-Improvement (CGI-I) Score Following Dose #1 of Staccato Loxapine, Compared With Placebo | Clinical Global Impression- Improvement (CGI-I) scores ranged from 1 to 7: 0=not assessed (missing), 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. | Baseline and 2 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Robert S Fishman, MD | Alexza Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Synergy Escondido | Escondido | California | 92025 | United States | ||
| Collaborative NeuroScience Network, Inc. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22329470 | Background | Kwentus J, Riesenberg RA, Marandi M, Manning RA, Allen MH, Fishman RS, Spyker DA, Kehne JH, Cassella JV. Rapid acute treatment of agitation in patients with bipolar I disorder: a multicenter, randomized, placebo-controlled clinical trial with inhaled loxapine. Bipolar Disord. 2012 Feb;14(1):31-40. doi: 10.1111/j.1399-5618.2011.00975.x. | |
| 29163985 |
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IPD submitted to regulatory authorities. Others may contact Alexza Pharmaceuticals, Inc. Please send your request to ClinicalTrialsInfo@alexza.com
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| ID | Title | Description |
|---|---|---|
| FG000 | Inhaled Placebo | Inhaled Staccato Placebo, may repeat after 2 hours x 2 Inhaled Placebo: Inhaled loxapine Placebo, may repeat after 2 hours x 2 |
| FG001 | Inhaled Loxapine 5 mg | Inhaled Staccato Loxapine 5 mg, may repeat after 2 hours x 2 Inhaled loxapine 5 mg: Inhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2 |
| FG002 | Inhaled Loxapine 10 mg | Inhaled Staccato Loxapine 10 mg, may repeat after 2 hours x 2 Inhaled loxapine 10 mg: Inhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Inhaled Placebo | Inhaled Staccato Placebo, may repeat after 2 hours x 2 Inhaled Placebo: Inhaled loxapine Placebo, may repeat after 2 hours x 2 |
| BG001 | Inhaled Loxapine 5 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in PANSS Excited Component (PEC) Score From Baseline Following Dose #1 of Staccato Loxapine, Compared With Placebo | The Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) comprises 5 items associated with agitation: poor impulse control, tension, hostility, uncooperativeness, and excitement; each scored 1 (min) to 7 (max). The PANSS-EC, the sum of these 5 subscales, thus ranges from 5 to 35. Individuals were eligible if they had a PANSS-EC of ≥14 (out of 35) and a score ≥4 (out of 7) on at least 1 of the 5 items. | ITT Population with LOCF | Posted | Mean | Standard Deviation | units on a scale | Baseline and 2 hours |
|
From informed consent through 30 days after last treatment
AEs were recorded when identified by the study center staff or volunteered by a patient.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Inhaled Placebo | Inhaled Staccato Placebo, may repeat after 2 hours x 2 Inhaled Placebo: Inhaled loxapine Placebo, may repeat after 2 hours x 2 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysgeusia | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
Because of the need to provide informed consent, the types of patients enrolled in the study may not have been representative of the most severely agitated patients who present for emergency care.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Scientific Officer | Alexza Pharmaceuticals, Inc | 650.944.7777 | :jcassella@alexza.com |
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| ID | Term |
|---|---|
| D011595 | Psychomotor Agitation |
| ID | Term |
|---|---|
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D011596 | Psychomotor Disorders |
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| ID | Term |
|---|---|
| D008152 | Loxapine |
| ID | Term |
|---|---|
| D003989 | Dibenzoxazepines |
| D006575 | Heterocyclic Compounds, 3-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| Inhaled loxapine 5 mg | Drug | Inhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2 |
|
|
| Inhaled loxapine 10 mg | Drug | Inhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2 |
|
|
| CGI-I Responders | Frequency of response based on the CGI-I (defined as achieving a CGI-I score of 1 or 2 at 2 hours after administration of the inhalation) | Baseline and 2 hours |
| Garden Grove |
| California |
| 92845 |
| United States |
| Atlanta Center for Medical Research | Atlanta | Georgia | 30308 | United States |
| FutureSearch Trials | Austin | Texas | 78756 | United States |
| Claghorn-Lesem Research Clinic | Houston | Texas | 77008 | United States |
| Northwest Clinical Research Center | Bellevue | Washington | 98004 | United States |
| Zeller S, Zun L, Cassella JV, Spyker DA, Yeung PP. Response to inhaled loxapine in patients with schizophrenia or bipolar I disorder: PANSS-EC responder analyses. BJPsych Open. 2017 Nov 10;3(6):285-290. doi: 10.1192/bjpo.bp.117.005363. eCollection 2017 Nov. |
Inhaled Staccato Loxapine 5 mg, may repeat after 2 hours x 2
Inhaled loxapine 5 mg: Inhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2
| BG002 | Inhaled Loxapine 10 mg | Inhaled Staccato Loxapine 10 mg, may repeat after 2 hours x 2 Inhaled loxapine 10 mg: Inhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2 |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| Inhaled Loxapine 5 mg |
Inhaled Staccato Loxapine 5 mg, may repeat after 2 hours x 2 Inhaled loxapine 5 mg: Inhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2 |
| OG002 | Inhaled Loxapine 10 mg | Inhaled Staccato Loxapine 10 mg, may repeat after 2 hours x 2 Inhaled loxapine 10 mg: Inhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2 |
|
|
|
| Secondary | Clinical Global Impression-Improvement (CGI-I) Score Following Dose #1 of Staccato Loxapine, Compared With Placebo | Clinical Global Impression- Improvement (CGI-I) scores ranged from 1 to 7: 0=not assessed (missing), 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse, 7=very much worse. | ITT Population with LOCF | Posted | Mean | Standard Deviation | units on a scale | Baseline and 2 hours |
|
|
|
|
| Secondary | CGI-I Responders | Frequency of response based on the CGI-I (defined as achieving a CGI-I score of 1 or 2 at 2 hours after administration of the inhalation) | ITT Population with LOCF | Posted | Count of Participants | Participants | Baseline and 2 hours |
|
|
|
| 0 |
| 105 |
| 0 |
| 105 |
| 26 |
| 105 |
| EG001 | Inhaled Loxapine 5 mg | Inhaled Staccato Loxapine 5 mg, may repeat after 2 hours x 2 Inhaled loxapine 5 mg: Inhaled Staccato loxapine 5 mg, may repeat after 2 hours x 2 | 0 | 104 | 0 | 104 | 35 | 104 |
| EG002 | Inhaled Loxapine 10 mg | Inhaled Staccato Loxapine 10 mg, may repeat after 2 hours x 2 Inhaled loxapine 10 mg: Inhaled Staccato loxapine 10 mg, may repeat after 2 hours x 2 | 0 | 105 | 0 | 105 | 31 | 105 |
| Dizziness | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Headache | Musculoskeletal and connective tissue disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Sedation | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
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| D019954 |
| Neurobehavioral Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000096762 | Aberrant Motor Behavior in Dementia |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| <0.0001 |
-values (adjusted) using Dunnett's t-test in main effects ANCOVA model |
| Superiority |