Staccato Loxapine in Migraine (Out Patient)

• Sponsor: Alexza Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00825500
• Collaborator: (none)
• Enrollment: 366
• Locations: 3
• Arms: 3
• Duration (Months): 7
• Patients Per Site: 122
• Patients Per Site Per Month: 17.5

Study Details

Study Description

Brief Summary

Assess the safety and efficacy of Staccato Loxapine in patients with moderate to severe migraine headache with or without aura in an outpatient setting.

Condition or Disease	Intervention/Treatment	Phase
Migraine Headache	Drug: Inhaled Placebo; Drug: Inhaled Loxapine 1.25 mg; Drug: Inhaled Loxapine 2.5 mg	Phase 2

Detailed Description

This study was designed to compare the safety and pharmacodynamic profiles of concomitant administration of single doses of ADASUVE and intramuscular (IM) lorazepam compared to that of each agent administered alone. Respiratory pharmacodynamics were monitored through recordings of respirations/minute and pulse oximetry. Other pharmacodynamic safety measures included effects on blood pressure, heart rate, sedation, and psychomotor measures of attention, information processing speed, reaction time, and coordination.

Study Design

• Study Type: Interventional
• Actual Enrollment: 366 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-center, Randomized, Double-Blind, Placebo-Controlled, Single Dose Efficacy and Safety Study of Staccato® Loxapine for Inhalation in Outpatients With Migraine Headache
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Inhaled Placebo Inhaled Staccato Placebo (0 mg)	Drug: Inhaled Placebo; Inhaled Staccato placebo (0 mg)
Active Comparator: Inhaled Loxapine 1.25 mg Inhaled Staccato Loxapine 1.25 mg, single dose	Drug: Inhaled Loxapine 1.25 mg; Inhaled Staccato Loxapine 1.25 mg, single dose
Experimental: Inhaled Loxapine 2.5 mg Inhaled Staccato Loxapine 2.5 mg, single dose	Drug: Inhaled Loxapine 2.5 mg; Inhaled Staccato Loxapine 1.25 mg, single dose

Outcome Measures

Primary Outcome Measures

1. Pain-Relief at 2 Hours Post-treatment [2 hours]

   Pain-Relief=pretreatment pain rating of 2 (moderate) or 3 (severe) and a rating of 0 (none) or 1 (mild) at the designated assessment time

Secondary Outcome Measures

1. Photophobia Free [2 hours]

   Free of Photophobia at 2 Hours Post-treatment

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

• Male or female between the ages of 18 to 65 years, inclusive

• History of migraine headache with or without aura (according to IHS Criteria 1.1 or 1.2 for diagnosis beginning at least 6 months prior to study entry) (International Headache Society Clinical Trials Subcommittee, 2000)

• At least 3 migraine attacks in the last 3 month period (but not more than 8 migraine attacks in the last month)

• Pain rating of moderate or severe (on a none-mild- moderate-severe scale) prior to dosing

• Agreed not to use the study drug within 72 hours of a prior migraine attack

• Agreed not to use any acute migraine or pain medication within 48 hours prior to dosing (including over-the-counter [OTC] products); medications for migraine prophylaxis other than those that were exclusionary were permitted if stable doses had been given for at least 30 days prior to screening

• Agreed not to use medications (including OTC products) for motion sickness, tinnitus, or vertigo within 48 hours prior to dosing.

• Were able to speak, read, and understand English and were willing and able to provide written informed consent on an IRB-approved form prior to the initiation of any study procedures

• Were willing and able to comply with the study schedule and requirements, and agreed to return to the clinic within 5 working days of use of the study drug

• In good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead electrocardiogram (ECG), blood chemistry profile, hematology, urinalysis, and in the opinion of the investigator

• Female participants (if of child-bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) who agreed to use a medically acceptable and effective birth control method throughout the study and for 1 week following the end of the study. Medically acceptable methods of contraception that could be used by the participant and/or his/her partner included abstinence, birth control pills or patches, diaphragm with spermicide, intrauterine device (IUD), condom with foam or spermicide, vaginal spermicidal suppository, surgical sterilization, and progestin implant or injection. Prohibited methods included the rhythm method, withdrawal, condoms alone, or diaphragm alone.

Exclusion Criteria

• Use of antipsychotics (including butryophenones, phenothiazines, thioxanthenes, aripiprazle, olanzapine, risperidone), tricyclic antidepressants, trazodone, anticonvulsants (except topiramate), barbiturates, benzodiazepines, or lithium within 14 days or 5 half-lives, whichever was longer, of randomization and at anytime throughout the study

• History of contraindications to anticholinergic agents (eg, bowel or urinary obstruction, stenosing peptic ulcers, narrow-angle glaucoma)

• History of allergy or intolerance to dibenzoxazepines (loxapine and amoxapine)

• History of extrapyramidal disorders, movement disorders including Parkinson's disease or neuroleptic malignant syndrome

• Female patients with a positive pregnancy test at screening or during randomization visit, or who were breastfeeding

• History within the past year of drug or alcohol dependence or abuse as defined by DSM IV

• History of syncope, unstable angina, myocardial infarction (within 6 months), congestive heart failure, or uncontrolled hypertension

• History of a major neurological disorder other than migraine (seizure disorder, subarachnoid bleeding, stroke, brain tumor, or transient ischemic attack)

• Any other disease(s), by history, physical examination, or laboratory abnormalities (including alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2-fold the upper limit of normal, total bilirubin > 1.5 mg/dL, or creatinine > 1.8 mg/dL), that in the investigator's opinion, would present undue risk to the patient or could confound the interpretation of study results

• History of asthma or chronic obstructive lung disease or any use of an inhaler prescribed for wheezing or bronchospasm in the past 5 years

• Receipt of an investigational drug within 30 days prior to the screening visit

• Considered by the investigator, for any reason, to be an unsuitable candidate for receiving loxapine, or unable to use the inhalation device

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Roger K. Cady	Springfield	Missouri	United States	65807
2	Elkind Headache Center	Mount Vernon	New York	United States	10550
3	CNS Research, Inc.	East Providence	Rhode Island	United States	02916

Sponsors and Collaborators

• Alexza Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Roger K. Cady, MD, Clinvest
• Principal Investigator: Peter J. Bellafiore, MD, CNS Research, Inc.
• Principal Investigator: Arthur Elkind, MD, Elkind Headache Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexza Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00825500
• Other Study ID Numbers: AMDC-104-202; 24-October-2008
• First Posted: Jan 21, 2009
• Last Update Posted: Apr 24, 2017
• Last Verified: Aug 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.: Migraine headache; Loxapine; Staccato
• Additional relevant MeSH terms: Migraine Disorders; Headache; Loxapine

Study Results

Participant Flow

Arm/Group Title	Inhaled Placebo	Inhaled Loxapine 1.25 mg	Inhaled Loxapine 2.5 mg
Arm/Group Description	Inhaled Staccato Placebo (0 mg) Inhaled Placebo: Inhaled Staccato placebo (0 mg)	Inhaled Staccato Loxapine 1.25 mg, single dose Inhaled Loxapine 1.25 mg: Inhaled Staccato Loxapine 1.25 mg, single dose	Inhaled Staccato Loxapine 2.5 mg, single dose Inhaled Loxapine 2.5 mg: Inhaled Staccato Loxapine 1.25 mg, single dose
Period Title: Overall Study
STARTED	125	121	120
COMPLETED	125	121	120
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Inhaled Placebo	Inhaled Loxapine 1.25 mg	Inhaled Loxapine 2.5 mg	Total
Arm/Group Description	Inhaled Staccato Placebo (0 mg) Inhaled Placebo: Inhaled Staccato placebo (0 mg)	Inhaled Staccato Loxapine 1.25 mg, single dose Inhaled Loxapine 1.25 mg: Inhaled Staccato Loxapine 1.25 mg, single dose	Inhaled Staccato Loxapine 2.5 mg, single dose Inhaled Loxapine 2.5 mg: Inhaled Staccato Loxapine 1.25 mg, single dose	Total of all reporting groups
Overall Participants	125	121	120	366
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	125 100%	121 100%	120 100%	366 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.5 (12.14)	41.2 (12.19)	42 (12.74)	41.5 (12.33)
Sex: Female, Male (Count of Participants)
Female	88 70.4%	100 82.6%	41 34.2%	229 62.6%
Male	37 29.6%	21 17.4%	79 65.8%	137 37.4%
Region of Enrollment (participants) [Number]
United States	125 100%	121 100%	120 100%	366 100%

Outcome Measures

1. Primary Outcome

Title	Pain-Relief at 2 Hours Post-treatment
Description	Pain-Relief=pretreatment pain rating of 2 (moderate) or 3 (severe) and a rating of 0 (none) or 1 (mild) at the designated assessment time
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

ITT with LOCF Population

Arm/Group Title	Inhaled Placebo	Inhaled Loxapine 1.25 mg	Inhaled Loxapine 2.5 mg
Arm/Group Description	Inhaled Staccato Placebo (0 mg) Inhaled Placebo: Inhaled Staccato placebo (0 mg)	Inhaled Staccato Loxapine 1.25 mg, single dose Inhaled Loxapine 1.25 mg: Inhaled Staccato Loxapine 1.25 mg, single dose	Inhaled Staccato Loxapine 2.5 mg, single dose Inhaled Loxapine 2.5 mg: Inhaled Staccato Loxapine 1.25 mg, single dose
Measure Participants	124	121	119
Count of Participants [Participants]	56 44.8%	65 53.7%	66 55%

2. Secondary Outcome

Title	Photophobia Free
Description	Free of Photophobia at 2 Hours Post-treatment
Time Frame	2 hours

Outcome Measure Data

Analysis Population Description

ITT with LOCF Population

Arm/Group Title	Inhaled Placebo	Inhaled Loxapine 1.25 mg	Inhaled Loxapine 2.5 mg
Arm/Group Description	Inhaled Staccato Placebo (0 mg) Inhaled Placebo: Inhaled Staccato placebo (0 mg)	Inhaled Staccato Loxapine 1.25 mg, single dose Inhaled Loxapine 1.25 mg: Inhaled Staccato Loxapine 1.25 mg, single dose	Inhaled Staccato Loxapine 2.5 mg, single dose Inhaled Loxapine 2.5 mg: Inhaled Staccato Loxapine 1.25 mg, single dose
Measure Participants	124	121	119
Count of Participants [Participants]	59 47.2%	47 38.8%	54 45%

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	Subjects were instructed to carry out self-assessment for adverse events from dosing through 24 hours and recored in the patient diary
Arm/Group Title	Inhaled Placebo		Inhaled Loxapine 1.25 mg		Inhaled Loxapine 2.5 mg
Arm/Group Description	Inhaled Staccato Placebo (0 mg) Inhaled Placebo: Inhaled Staccato placebo (0 mg)		Inhaled Staccato Loxapine 1.25 mg, single dose Inhaled Loxapine 1.25 mg: Inhaled Staccato Loxapine 1.25 mg, single dose		Inhaled Staccato Loxapine 2.5 mg, single dose Inhaled Loxapine 2.5 mg: Inhaled Staccato Loxapine 1.25 mg, single dose
All Cause Mortality
	Inhaled Placebo		Inhaled Loxapine 1.25 mg		Inhaled Loxapine 2.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/125 (0%)		0/121 (0%)		0/120 (0%)
Serious Adverse Events
	Inhaled Placebo		Inhaled Loxapine 1.25 mg		Inhaled Loxapine 2.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/125 (0%)		0/121 (0%)		0/120 (0%)
Other (Not Including Serious) Adverse Events
	Inhaled Placebo		Inhaled Loxapine 1.25 mg		Inhaled Loxapine 2.5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/125 (17.6%)		27/121 (22.3%)		24/120 (20%)
Gastrointestinal disorders
Dysgeusia	6/125 (4.8%)	6	16/121 (13.2%)	16	10/120 (8.3%)	10
Nervous system disorders
Dizziness	12/125 (9.6%)	12	8/121 (6.6%)	8	6/120 (5%)	6
Somnolence	4/125 (3.2%)	4	3/121 (2.5%)	3	8/120 (6.7%)	8

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.