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Phase 3 safety and efficacy study of Staccato Loxapine in the treatment of acute agitation in schizophrenic 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 Loxapine 5 mg | Experimental | Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours |
|
| Inhaled Loxapine 10 mg | Experimental | Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours |
|
| Inhaled placebo | Placebo Comparator | Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Inhaled loxapine 5 mg | Drug | Inhaled loxapine 5 mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in PANSS-EC From Baseline | 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 | 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 |
| CGI-I Responders |
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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 |
|---|---|---|---|---|---|---|
| Atlanta Center for Medical Research | Atlanta | Georgia | 30308 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21200077 | Background | Lesem MD, Tran-Johnson TK, Riesenberg RA, Feifel D, Allen MH, Fishman R, Spyker DA, Kehne JH, Cassella JV. Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine. Br J Psychiatry. 2011 Jan;198(1):51-8. doi: 10.1192/bjp.bp.110.081513. | |
| 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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During the Pre-treatment Period, agitated schizophrenic patients were screened for inclusion in the study. This period lasted until the evaluations were begun.
The study was conducted at 24 centers - all in the US. Patients recruited for screening were admitted to a hospital or research unit with acute agitation, and were being treated for chronic underlying schizophrenia.
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| ID | Title | Description |
|---|---|---|
| FG000 | Inhaled Placebo | Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours |
| FG001 | Inhaled Loxapine 5 mg | Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours |
| FG002 | Inhaled Loxapine 10 mg | Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Inhaled Placebo | Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours |
| BG001 | Inhaled Loxapine 5 mg | Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours |
| 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-EC From Baseline | 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 Loxapine placebo, may repeat x 1 or 2 after 2 hours | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Exacerbation of schizophrenia | Psychiatric disorders | MedDRA 10.0 | Non-systematic Assessment | A 45 year-old white male assigned to the Placebo group experienced a severe exacerbation of schizophrenia and was hospitalized. |
| 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 | |
|---|---|---|---|---|
| Executive VP, Research & Development, Regulatory & Quality | Alexza Pharmaceuticals, Inc | 650.944.7071 | ClinicalTrialsInfo@alexza.com |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| D011595 | Psychomotor Agitation |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
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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 10 mg | Drug | Inhaled loxapine 10 mg |
|
|
| Inhaled placebo | Drug | Inhaled placebo |
|
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 |
| 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. |
| BG002 | Inhaled Loxapine 10 mg | Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours |
| 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 |
|
Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours
| OG002 | Inhaled Loxapine 10 mg | Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours |
|
|
|
| Secondary | Clinical Global Impression-Improvement (CGI-I) Score | 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 |
|
|
|
|
| 115 |
| 1 |
| 115 |
| 44 |
| 115 |
| EG001 | Inhaled Loxapine 5 mg | Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours | 0 | 116 | 0 | 116 | 35 | 116 |
| EG002 | Inhaled Loxapine 10 mg | Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours | 0 | 113 | 1 | 113 | 41 | 113 |
|
| Gastroenteritis | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment | A 37 year-old female assigned to the Staccato Loxapine 10-mg group had severe gastroenteritis that resulted in hospitalization. This event was reported as an SAE, was judged unrelated to study treatment |
|
| Nausea | Gastrointestinal disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
| Sedation | Nervous system disorders | MedDRA 10.0 | Non-systematic Assessment |
|
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
| D009422 | Nervous System Diseases |
| D011596 | Psychomotor Disorders |
| D019954 | Neurobehavioral Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000096762 | Aberrant Motor Behavior in Dementia |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| Superiority |
| Superiority |