Staccato Loxapine Pulmonary Safety in Healthy Volunteers

• Sponsor: Alexza Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00789360
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 5
• Patients Per Site Per Month: 6

Study Details

Study Description

Brief Summary

The objective of this trial is to assess the pulmonary safety of 2 inhaled doses of Staccato Loxapine within a day.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Inhaled Placebo; Drug: Inhaled Loxapine	Phase 1

Detailed Description

The planned study is a multiple dose, double-blind, placebo-controlled, randomized, 2-sequence, 2-period crossover study investigating pulmonary safety in healthy volunteers.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Pulmonary Safety of Repeat Doses of Staccato® Loxapine for Inhalation in Healthy Volunteers
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Inhaled Placebo crossed over to Inhaled Loxapine Inhaled Staccato Placebo, 2 inhalations, 8 hours apart; washout of at least 4 days; Inhaled Staccato Loxapine, 10 mg oses x 2, 8 hours apart	Drug: Inhaled Placebo; Inhaled Staccato Placebo, 2 inhalations, 8 hours apart; Drug: Inhaled Loxapine; Inhaled Staccato Loxapine, 10 mg doses x 2, 8 hours apart
Experimental: Inhaled Loxapine crossed over to Inhaled Placebo Inhaled Staccato Loxapine, 10 mg doses x 2, 8 hours apart; washout of at least 4 days; Inhaled Staccato Placebo, 2 inhalations, 8 hours apart;	Drug: Inhaled Placebo; Inhaled Staccato Placebo, 2 inhalations, 8 hours apart; Drug: Inhaled Loxapine; Inhaled Staccato Loxapine, 10 mg doses x 2, 8 hours apart

Outcome Measures

Primary Outcome Measures

1. The Largest Treatment Difference (Loxapine - Placebo) in Change in FEV1 From Baseline by Spirometry [17 post-treatment time points (15 min to 32 hr)]

   The largest treatment difference (Loxapine - Placebo) across the 17 post-treatment time points (15 min to 32 hr) in FEV1 Change from Same-Period Baseline,

Secondary Outcome Measures

1. The Largest Treatment Difference (Loxapine - Placebo) in Change in FVC From Baseline by Spirometry [17 post-treatment time points (15 min to 32 hr)]

   The largest treatment difference (Loxapine - Placebo) across the 17 post-treatment time points (15 min to 32 hr) in FVC Change from Same-Period Baseline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• nonsmoker subjects in good general health with normal spirometry at screening AND baseline

Exclusion Criteria:

• history of asthma, COPD, or any other acute or chronic pulmonary disease or bronchodilator use

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northeast Medical Research	North Dartmouth	Massachusetts	United States	02747

Sponsors and Collaborators

• Alexza Pharmaceuticals, Inc.

Investigators

• Principal Investigator: David S. Miller, MD, Northeast Medical Research, North Dartmouth, MA

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexza Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00789360
• Other Study ID Numbers: AMDC-004-104; 12 September 2008
• First Posted: Nov 11, 2008
• Last Update Posted: Mar 11, 2019
• Last Verified: May 1, 2009

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alexza Pharmaceuticals, Inc.: Healthy volunteers
• Additional relevant MeSH terms: Loxapine

Study Results

Participant Flow

Recruitment Details	Each investigator obtained approval from their IRB for their advertisements and other subject recruitment procedures
Pre-assignment Detail	At screening and before administration of Dose 1 in each treatment period, the following were confirmed: forced expiratory volume in 1 second (FEV1) ≥85% of predicted, forced vital capacity (FVC) ≥85% of predicted, and oxygen saturation by pulse oximetry (SpO2) ≥95% on room air.

Arm/Group Title	Inhaled Placebo / Loxapine	Inhaled Loxapine / Placebo
Arm/Group Description	Inhaled Staccato Placebo, 2 inhalations, 8 hours apart followed by Inhaled Staccato Loxapine, 10 mg doses x 2, 8 hours apart	Inhaled Staccato Loxapine, 10 mg oses x 2, 8 hours apart followed by Inhaled Staccato Placebo, 2 inhalations, 8 hours apart
Period Title: Overall Study
STARTED	15	15
COMPLETED	12	14
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Inhaled Placebo / Loxapine	Inhaled Loxapine / Placebo	Total
Arm/Group Description	Inhaled Staccato Placebo, 2 inhalations, 8 hours apart followed by Inhaled Staccato Loxapine, 10 mg doses x 2, 8 hours apart	Inhaled Staccato Loxapine, 10 mg oses x 2, 8 hours apart followed by Inhaled Staccato Placebo, 2 inhalations, 8 hours apart	Total of all reporting groups
Overall Participants	15	15	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	15 100%	30 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.4 (13.65)	28.7 (9.75)	30 (11.74)
Sex: Female, Male (Count of Participants)
Female	5 33.3%	5 33.3%	10 33.3%
Male	10 66.7%	10 66.7%	20 66.7%
Region of Enrollment (Count of Participants)
United States	15 100%	15 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	The Largest Treatment Difference (Loxapine - Placebo) in Change in FEV1 From Baseline by Spirometry
Description	The largest treatment difference (Loxapine - Placebo) across the 17 post-treatment time points (15 min to 32 hr) in FEV1 Change from Same-Period Baseline,
Time Frame	17 post-treatment time points (15 min to 32 hr)

Outcome Measure Data

Analysis Population Description

Crossover Spirometry Population (all subjects receiving both inhaled loxapine and inhaled placebo) LSM and CI statistics were based on the individual (within subject) differences between loxapine and placebo exposures

Arm/Group Title	Inhaled Loxapine	Inhaled Staccato Placebo
Arm/Group Description	Inhaled Staccato Loxapine, 10 mg doses x 2, 8 hours apart	Inhaled Staccato Placebo, 2 inhalations, 8 hours apart
Measure Participants	23	25
Least Squares Mean (90% Confidence Interval) [liters]	-0.1042	-0.1025

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Loxapine, Inhaled Staccato Placebo
	Comments	The largest treatment difference (Loxapine - Placebo) in change in FEV1 from baseline by spirometry
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum LS mean change difference
	Estimated Value	0.0917
	Confidence Interval	(2-Sided) 90%; -0.028 to 0.212
	Parameter Dispersion	Type: Value:
	Estimation Comments	Maximum difference occurred at 10 hours

2. Secondary Outcome

Title	The Largest Treatment Difference (Loxapine - Placebo) in Change in FVC From Baseline by Spirometry
Description	The largest treatment difference (Loxapine - Placebo) across the 17 post-treatment time points (15 min to 32 hr) in FVC Change from Same-Period Baseline
Time Frame	17 post-treatment time points (15 min to 32 hr)

Outcome Measure Data

Analysis Population Description

Crossover Spirometry Population (all subjects receiving both inhaled loxapine and inhaled placebo) LSM and CI statistics were based on the individual (within subject) differences between loxapine and placebo exposures

Arm/Group Title	Inhaled Loxapine	Inhaled Staccato
Arm/Group Description	Inhaled Staccato Loxapine, 10 mg doses x 2, 8 hours apart	Inhaled Staccato Placebo, 2 inhalation, 8 hours apart
Measure Participants	25	25
Least Squares Mean (90% Confidence Interval) [liters]	-0.271	-0.149

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Inhaled Loxapine, Inhaled Staccato Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Maximum LS mean change difference
	Estimated Value	-0.154
	Confidence Interval	(2-Sided) 90%; -0.290 to -0.019
	Parameter Dispersion	Type: Value:
	Estimation Comments	Greatest difference occurred at 9 hours after Dose 1

Adverse Events

Time Frame	Adverse events (AEs) were considered treatment related from the first exposure to study treatment until 30 days after the last treatment
Adverse Event Reporting Description	Adverse events (AEs) were assessed predose and at 16 pre-specified time points for the 24-hour period after dosing, as well as whenever spontaneously reported by the subjects or study staff
Arm/Group Title	Inhaled Placebo		Inhaled Loxapine
Arm/Group Description	Inhaled Staccato Placebo, 2 inhalations, 8 hours apart Inhaled Placebo: Inhaled Staccato Placebo, 2 inhalations, 8 hours apart		Inhaled Staccato Loxapine, 10 mg doses x 2, 8 hours apart Inhaled Loxapine: Inhaled Staccato Loxapine, 10 mg doses x 2, 8 hours apart
All Cause Mortality
	Inhaled Placebo		Inhaled Loxapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/29 (0%)		0/27 (0%)
Serious Adverse Events
	Inhaled Placebo		Inhaled Loxapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/29 (3.4%)		0/27 (0%)
Gastrointestinal disorders
Appendicitis	1/29 (3.4%)	1	0/27 (0%)	0
Other (Not Including Serious) Adverse Events
	Inhaled Placebo		Inhaled Loxapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/29 (17.2%)		16/27 (59.3%)
Gastrointestinal disorders
Dysgeusia	1/29 (3.4%)	1	12/27 (44.4%)	12
Vomiting	0/29 (0%)	0	2/27 (7.4%)	2
Nervous system disorders
Dizziness	0/29 (0%)	0	2/27 (7.4%)	2
Headache	4/29 (13.8%)	4	2/27 (7.4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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. The sponsor cannot require changes to the communication and cannot extend the embargo.