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Staccato Loxapine in Agitated Patients With Schizophrenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00628589
Recruitment Status : Completed
First Posted : March 5, 2008
Results First Posted : June 29, 2017
Last Update Posted : July 26, 2017
Sponsor:
Information provided by (Responsible Party):
Alexza Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Patients With Schizophrenia and Acute Agitation
Interventions Drug: Inhaled loxapine 5 mg
Drug: Inhaled loxapine 10 mg
Drug: Inhaled placebo
Enrollment 344
Recruitment Details 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.
Pre-assignment Details During the Pre-treatment Period, agitated schizophrenic patients were screened for inclusion in the study. This period lasted until the evaluations were begun.
Arm/Group Title Inhaled Placebo Inhaled Loxapine 5 mg Inhaled Loxapine 10 mg
Hide Arm/Group Description Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours
Period Title: Overall Study
Started 115 116 113
Completed 114 114 110
Not Completed 1 2 3
Arm/Group Title Inhaled Placebo Inhaled Loxapine 5 mg Inhaled Loxapine 10 mg Total
Hide Arm/Group Description Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours Total of all reporting groups
Overall Number of Baseline Participants 115 116 113 344
Hide Baseline Analysis Population Description
Safety Population
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 116 participants 113 participants 344 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
115
 100.0%
116
 100.0%
113
 100.0%
344
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants 116 participants 113 participants 344 participants
43.9  (9.45) 43.2  (10.24) 42.2  (9.82) 43.1  (9.84)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 116 participants 113 participants 344 participants
Female
35
  30.4%
29
  25.0%
27
  23.9%
91
  26.5%
Male
80
  69.6%
87
  75.0%
86
  76.1%
253
  73.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 115 participants 116 participants 113 participants 344 participants
115 116 113 344
1.Primary Outcome
Title Change in PANSS-EC From Baseline
Hide Description 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.
Time Frame Baseline and 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF
Arm/Group Title Inhaled Placebo Inhaled Loxapine 5 mg Inhaled Loxapine 10 mg
Hide Arm/Group Description:
Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours
Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours
Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours
Overall Number of Participants Analyzed 115 116 112
Mean (Standard Deviation)
Unit of Measure: units on a scale
-5.5  (4.92) -8.1  (5.17) -8.6  (4.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inhaled Placebo, Inhaled Loxapine 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments LS mean was used in the primary efficacy analysis
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments p-values (adjusted) using Dunnett's t-test in main effects ANCOVA model
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inhaled Placebo, Inhaled Loxapine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments p-values (adjusted) using Dunnett's t-test in main effects ANCOVA model
2.Secondary Outcome
Title Clinical Global Impression-Improvement (CGI-I) Score
Hide Description 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.
Time Frame Baseline and 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF
Arm/Group Title Inhaled Placebo Inhaled Loxapine 5 mg Inhaled Loxapine 10 mg
Hide Arm/Group Description:
Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours
Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours
Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours
Overall Number of Participants Analyzed 115 116 112
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.8  (1.11) 2.3  (1.24) 2.1  (1.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inhaled Placebo, Inhaled Loxapine 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inhaled Placebo, Inhaled Loxapine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title CGI-I Responders
Hide Description 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)
Time Frame Baseline and 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population with LOCF
Arm/Group Title Inhaled Placebo Inhaled Loxapine 5 mg Inhaled Loxapine 10 mg
Hide Arm/Group Description:
Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours
Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours
Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours
Overall Number of Participants Analyzed 115 116 112
Measure Type: Count of Participants
Unit of Measure: Participants
41
  35.7%
66
  56.9%
75
  67.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inhaled Placebo, Inhaled Loxapine 5 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0015
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inhaled Placebo, Inhaled Loxapine 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Time Frame From informed consent through 30 days after last treatment
Adverse Event Reporting Description AEs were recorded when identified by the study center staff or volunteered by a patient.
 
Arm/Group Title Inhaled Placebo Inhaled Loxapine 5 mg Inhaled Loxapine 10 mg
Hide Arm/Group Description Inhaled Loxapine placebo, may repeat x 1 or 2 after 2 hours Inhaled Loxapine 5 mg, may repeat x 1 or 2 after 2 hours Inhaled Loxapine 10 mg, may repeat x 1 or 2 after 2 hours
All-Cause Mortality
Inhaled Placebo Inhaled Loxapine 5 mg Inhaled Loxapine 10 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/115 (0.00%)      0/116 (0.00%)      0/113 (0.00%)    
Hide Serious Adverse Events
Inhaled Placebo Inhaled Loxapine 5 mg Inhaled Loxapine 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/115 (0.87%)      0/116 (0.00%)      1/113 (0.88%)    
Gastrointestinal disorders       
Gastroenteritis * 1 [1]  0/115 (0.00%)  0 0/116 (0.00%)  0 1/113 (0.88%)  1
Psychiatric disorders       
Exacerbation of schizophrenia * 1 [2]  1/115 (0.87%)  1 0/116 (0.00%)  0 0/113 (0.00%)  0
1
Term from vocabulary, MedDRA 10.0
*
Indicates events were collected by non-systematic assessment
[1]
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
[2]
A 45 year-old white male assigned to the Placebo group experienced a severe exacerbation of schizophrenia and was hospitalized.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Inhaled Placebo Inhaled Loxapine 5 mg Inhaled Loxapine 10 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/115 (38.26%)      35/116 (30.17%)      41/113 (36.28%)    
Gastrointestinal disorders       
Dysgeusia * 1  3/115 (2.61%)  3 10/116 (8.62%)  10 12/113 (10.62%)  12
Nausea * 1  6/115 (5.22%)  6 1/116 (0.86%)  1 2/113 (1.77%)  2
Nervous system disorders       
Dizziness * 1  11/115 (9.57%)  11 6/116 (5.17%)  6 12/113 (10.62%)  12
Headache * 1  16/115 (13.91%)  16 3/116 (2.59%)  3 3/113 (2.65%)  3
Sedation * 1  11/115 (9.57%)  11 15/116 (12.93%)  15 12/113 (10.62%)  12
1
Term from vocabulary, MedDRA 10.0
*
Indicates events were collected by 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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Executive VP, Research & Development, Regulatory & Quality
Organization: Alexza Pharmaceuticals, Inc
Phone: 650.944.7071
EMail: ClinicalTrialsInfo@alexza.com
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Alexza Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00628589    
Other Study ID Numbers: AMDC-004-301
First Submitted: February 25, 2008
First Posted: March 5, 2008
Results First Submitted: February 4, 2017
Results First Posted: June 29, 2017
Last Update Posted: July 26, 2017