Trial Outcomes & Findings for Staccato Loxapine in Agitation (Proof of Concept) (NCT NCT00369577)

NCT ID: NCT00369577

Last Updated: 2018-01-02

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 129 participants
• Primary outcome timeframe: 2 hours
• Results posted on: 2018-01-02

Participant Flow

The study was conducted at 19 centers between Sep-2006 and Jan-2007. Patients recruited for screening were: 1) admitted to a hospital or research unit with acute agitation, 2) inpatients being treated for chronic underlying conditions who presented with acute agitation, and 3) patients with agitation treated in a psychiatric ED.

Pre-Treatment Period was defined as the period immediately prior to dosing in which screening procedures and inclusion/exclusion criteria were used to evaluate all patients for eligibility to participate in the study.

Participant milestones

Measure	Inhaled Placebo Inhaled Staccato Placebo, single dose	Inhaled Loxapine 5 mg Inhaled Staccato Loxapine 5 mg, single dose	Inhaled Loxapine 10 mg Inhaled Staccato Loxapine 10 mg, single dose
Overall Study STARTED	43	45	41
Overall Study COMPLETED	43	45	40
Overall Study NOT COMPLETED	0	0	1

Reasons for withdrawal

Measure	Inhaled Placebo Inhaled Staccato Placebo, single dose	Inhaled Loxapine 5 mg Inhaled Staccato Loxapine 5 mg, single dose	Inhaled Loxapine 10 mg Inhaled Staccato Loxapine 10 mg, single dose
Overall Study Withdrawal by Subject	0	0	1

Baseline Characteristics

Staccato Loxapine in Agitation (Proof of Concept)

Baseline characteristics by cohort

Measure	Inhaled Placebo n=43 Participants Inhaled Staccato Placebo, single dose	Inhaled Loxapine 5 mg n=45 Participants Inhaled Staccato Loxapine 5 mg, single dose	Inhaled Loxapine 10 mg n=41 Participants Inhaled Staccato Loxapine 10 mg, single dose	Total n=129 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	43 Participants n=5 Participants	45 Participants n=7 Participants	41 Participants n=5 Participants	129 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	43.5 years STANDARD_DEVIATION 7.7 • n=5 Participants	40.8 years STANDARD_DEVIATION 7.45 • n=7 Participants	39.3 years STANDARD_DEVIATION 8.77 • n=5 Participants	41.2 years STANDARD_DEVIATION 8.09 • n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants	24 Participants n=4 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	38 Participants n=7 Participants	34 Participants n=5 Participants	105 Participants n=4 Participants
Region of Enrollment United States	43 participants n=5 Participants	45 participants n=7 Participants	41 participants n=5 Participants	129 participants n=4 Participants

PRIMARY outcome

Timeframe: 2 hours

Population: The ITT population consisted of all patients who took any study medication and had both baseline data and at least 1 efficacy assessment after the. Any observation recorded after the use of rescue medication was censored and subject to the last observation carried forward algorithm.

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.

Outcome measures

Measure	Inhaled Placebo n=43 Participants Inhaled Staccato Placebo, single dose	Inhaled Loxapine 5 mg n=45 Participants Inhaled Staccato Loxapine 5 mg, single dose	Inhaled Loxapine 10 mg n=41 Participants Inhaled Staccato Loxapine 10 mg, single dose
PANSS-EC Change From Baseline	-4.98 PANSS units Standard Deviation 4.13	-6.71 PANSS units Standard Deviation 5.14	-8.56 PANSS units Standard Deviation 4.9

SECONDARY outcome

Timeframe: 2 hours

Population: All patients receiving experimental treatment

Change from baseline on the Behavioral Activity Rating Scale (BARS) ranging from 1 to 7 where: 1 = difficult or unable to rouse, 2 = asleep but responds normally to verbal or physical contact, 3 = drowsy, appears sedated, 4 = quiet, and awake (normal level of activity), 5 = signs of overt (physical or verbal) activity, calms down with instructions, 6 = extremely or continuously active, not requiring restraint, 7 = violent, requires restraint.

Outcome measures

Measure	Inhaled Placebo n=43 Participants Inhaled Staccato Placebo, single dose	Inhaled Loxapine 5 mg n=45 Participants Inhaled Staccato Loxapine 5 mg, single dose	Inhaled Loxapine 10 mg n=41 Participants Inhaled Staccato Loxapine 10 mg, single dose
BARS Change From Baseline After Drug Treatment	-0.930 BARS Score, Change from Baseline, units Standard Deviation 0.936	-1.53 BARS Score, Change from Baseline, units Standard Deviation 1.38	-2.02 BARS Score, Change from Baseline, units Standard Deviation 1.35

SECONDARY outcome

Timeframe: 2 hours

Population: All patients receiving treatment

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.

Outcome measures

Measure	Inhaled Placebo n=43 Participants Inhaled Staccato Placebo, single dose	Inhaled Loxapine 5 mg n=45 Participants Inhaled Staccato Loxapine 5 mg, single dose	Inhaled Loxapine 10 mg n=40 Participants Inhaled Staccato Loxapine 10 mg, single dose
Clinical Global Impressions-Improvement Scale (CGI-I) After Drug Administration	3.19 CGI-I Units (7=worse, 1=better) Standard Deviation 0.932	2.53 CGI-I Units (7=worse, 1=better) Standard Deviation 1.10	2.28 CGI-I Units (7=worse, 1=better) Standard Deviation 1.18

SECONDARY outcome

Timeframe: 2 hours

Population: All patients treated

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)

Outcome measures

Measure	Inhaled Placebo n=43 Participants Inhaled Staccato Placebo, single dose	Inhaled Loxapine 5 mg n=45 Participants Inhaled Staccato Loxapine 5 mg, single dose	Inhaled Loxapine 10 mg n=40 Participants Inhaled Staccato Loxapine 10 mg, single dose
CGI-I Responders	9 Participants	22 Participants	25 Participants

Adverse Events

Inhaled Placebo

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Inhaled Loxapine 5 mg

Serious events: 1 serious events

Other events: 14 other events

Deaths: 0 deaths

Inhaled Loxapine 10 mg

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Measure	Inhaled Placebo n=43 participants at risk Inhaled Staccato Placebo, single dose	Inhaled Loxapine 5 mg n=45 participants at risk Inhaled Staccato Loxapine 5 mg, single dose	Inhaled Loxapine 10 mg n=41 participants at risk Inhaled Staccato Loxapine 10 mg, single dose
Injury, poisoning and procedural complications Overdose	2.3% 1/43 • Number of events 1 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	0.00% 0/45 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	0.00% 0/41 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.
Vascular disorders Worsening of hypertension	0.00% 0/43 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	2.2% 1/45 • Number of events 1 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	0.00% 0/41 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.
Psychiatric disorders Exacerbation of schizophrenia	0.00% 0/43 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	0.00% 0/45 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	2.4% 1/41 • Number of events 1 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.

Other adverse events

Measure	Inhaled Placebo n=43 participants at risk Inhaled Staccato Placebo, single dose	Inhaled Loxapine 5 mg n=45 participants at risk Inhaled Staccato Loxapine 5 mg, single dose	Inhaled Loxapine 10 mg n=41 participants at risk Inhaled Staccato Loxapine 10 mg, single dose
Gastrointestinal disorders Dysgeusia	9.3% 4/43 • Number of events 4 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	4.4% 2/45 • Number of events 2 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	17.1% 7/41 • Number of events 7 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.
Nervous system disorders Dizziness	9.3% 4/43 • Number of events 4 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	11.1% 5/45 • Number of events 5 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	4.9% 2/41 • Number of events 2 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.
Nervous system disorders Headache	2.3% 1/43 • Number of events 1 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	4.4% 2/45 • Number of events 2 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	12.2% 5/41 • Number of events 5 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.
Nervous system disorders Sedation	14.0% 6/43 • Number of events 6 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	13.3% 6/45 • Number of events 6 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.	22.0% 9/41 • Number of events 9 • From informed consent through 30 days after last treatment Adverse events observed by the Investigator or study personnel during study assessments or when volunteered by the patient were recorded on the Adverse Event CRF. The severity of the AE and relationship to study drug was determined by the investigator. Medications used to treat the adverse event were recorded on the Concomitant Medication CRF.

Additional Information

Executive VP, Research & Development, Regulatory & Quality

Alexza Pharmaceuticals, Inc

Phone: 650.944.7071

Email: ClinicalTrialsInfo@alexza.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60