Staccato Loxapine in Migraine (in Clinic)

• Sponsor: Alexza Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00489476
• Collaborator: (none)
• Enrollment: 168
• Location: 1
• Arms: 4
• Duration (Months): 6
• Patients Per Site Per Month: 27.9

Study Details

Study Description

Brief Summary

The objective of this trial is to assess the efficacy and safety of Staccato Loxapine in patients with migraine headache with or without aura in a clinical setting.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: Staccato Loxapine; Drug: Staccato Placebo	Phase 2

Detailed Description

This study will enroll male and female patients with migraine headache with or without aura.

The study will randomize ~160 patients, 1:1:1:1 to receive one of the following treatments:

1.25 mg Staccato Loxapine; 2.5 mg Staccato Loxapine; 5 mg Staccato Loxapine; Staccato Placebo.

Study Design

• Study Type: Interventional
• Actual Enrollment: 168 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• 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 Patients With Migraine Headache
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1.25 mg Staccato Loxapine 1.25 mg ADASUVE, single dose	Drug: Staccato Loxapine; Other Names: ADASUVE
Experimental: 2.5 mg Staccato Loxapine 2.5 mg ADASUVE, single dose	Drug: Staccato Loxapine; Other Names: ADASUVE
Experimental: 5 mg Staccato Loxapine 5 mg ADASUVE, single dose	Drug: Staccato Loxapine; Other Names: ADASUVE
Experimental: Staccato Placebo Staccato Placebo, 0 mg	Drug: Staccato Placebo; Placebo aerosol inhalation (0mg)

Outcome Measures

Primary Outcome Measures

1. Pain-relief Response (Pain Severity of NONE or MILD) at 2 Hours [Baseline and 2 h post-dose]

   The primary efficacy endpoint was Pain-relief response as defined by the International Headache Society (Pain-IHS) as a pain severity of NONE or MILD. Intent to treat (ITT) with last observation carried forward (LOCF)

Secondary Outcome Measures

1. Pain-free at 2 Hours [Baseline and 2 h post-dose]

   Pain-free (Pain-IHS) at the 2 hour time point

Other Outcome Measures

1. Responders, Sustained Freedom From Pain [Baseline through 24 h post-dose]

   The percentages of patients with sustained freedom from pain (pain-free at 2 hours after dosing with no rescue medication and no recurrence of headache from 2 to 24 hours)

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Male and female patients between the ages of 18 to 65 years, inclusive.

2. Patients who have migraine headache with or without aura (diagnosis according to International Headache Society guidelines) for at least 6 months.

3. Patients who have a history of migraine and have had at least 3 migraine attacks in the last 3 month period (but not more than 8 migraine attacks in the last month).

4. Patients who have been pain free for at least 48 hours since the end of their last migraine attack.

5. Patients who have not taken any acute migraine or pain medication within 48 hours prior to dosing (including OTC products).

6. Patients who have a pain rating of Moderate or Severe (on a None-Mild- Moderate-Severe Scale) prior to dosing.

7. Patients who speak, read, and understand English and are willing and able to provide written informed consent on an IRB approved form prior to the initiation of any study procedures.

8. Patients who are willing and able to comply with the study schedule and requirements, are willing and able to travel to the Clinical Research Unit (CRU) for treatment and stay at the CRU for approximately a 4-6 hour period, and agree to return to the clinic within 5 working days of use of the investigational treatment.

9. Patients who are in good general health prior to study participation as determined by a detailed medical history, physical examination, 12-lead ECG, blood chemistry profile, hematology, urinalysis, and in the opinion of the Principal Investigator.

10. Female participants (if of child-bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) who agree to use a medically acceptable and effective birth control method throughout the study and for one week following the end of the study. Medically acceptable methods of contraception that may be used by the participant and/or his/her partner include 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 include: the rhythm method, withdrawal, condoms alone, or diaphragm alone.

Exclusion Criteria:

1. Patients who are currently taking antipsychotics, tricyclic antidepressants, valproate, barbiturates, benzodiazepines, or lithium must be excluded.

2. Patients with a history of contraindications to anticholinergics (bowel obstruction, urinary retention, acute glaucoma) must be excluded.

3. Patients with a history of allergy or intolerance to dibenzoxazepines (loxapine and amoxapine) must be excluded.

4. Patients with a history of extra-pyramidal disorders, movement disorders including Parkinson's disease, and patients with a history of neuroleptic malignant syndrome must be excluded.

5. Female patients who have a positive pregnancy test at screening or during randomization visit, or are breastfeeding must be excluded.

6. Patients who have a history within the past year of drug or alcohol dependence or abuse as defined by DSM-4 must be excluded.

7. Patients who have a history of syncope, unstable angina, myocardial infarction (within 6 months), congestive heart failure, transient ischemic attack, or pheochromocytoma must be excluded.

8. Patients who have a history of a major neurological disorder other than migraine (seizure disorder, subarachnoid bleeding, stroke, brain tumor) must be excluded.

9. Patients who have any other disease(s), by history, physical examination, or laboratory abnormalities (ALT or AST > 2-fold the upper limit of normal, Bilirubin > 1.5 mg/dL, or creatinine > 1.8 mg/dL) or that in the investigator's opinion, would present undue risk to the patient or may confound the interpretation of study results must be excluded.

10. Patients who have a history of asthma or chronic obstructive lung disease should be excluded.

11. Patients who have received an investigational drug within 30 days prior to the Screening Visit must be excluded.

12. Patients who are considered by the investigator, for any reason, to be an unsuitable candidate for receiving loxapine, or unable to use the inhalation device, must be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medvadis	Wellesley Hills	Massachusetts	United States	02481-2106

Sponsors and Collaborators

• Alexza Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Egilius Spierings, MD, MedVadis Research Corporation

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alexza Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT00489476
• Other Study ID Numbers: AMDC-104-201
• First Posted: Jun 21, 2007
• Last Update Posted: Jul 6, 2017
• Last Verified: Apr 1, 2008

• 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.: Staccato® Loxapine, Migraine
• Additional relevant MeSH terms: Migraine Disorders; Loxapine

Study Results

Participant Flow

Arm/Group Title	Staccato Placebo	1.25 mg Staccato Loxapine	2.5 mg Staccato Loxapine	5 mg Staccato Loxapine
Arm/Group Description	Staccato Placebo, 0 mg Staccato Placebo: Placebo aerosol inhalation (0mg)	1.25 mg ADASUVE, single dose Staccato Loxapine	2.5 mg ADASUVE, single dose Staccato Loxapine	5 mg ADASUVE, single dose Staccato Loxapine
Period Title: Overall Study
STARTED	39	43	43	43
COMPLETED	39	42	43	43
NOT COMPLETED	0	1	0	0

Baseline Characteristics

Arm/Group Title	Staccato Placebo	1.25 mg Staccato Loxapine	2.5 mg Staccato Loxapine	5 mg Staccato Loxapine	Total
Arm/Group Description	Staccato Placebo, 0 mg Staccato Placebo: Placebo aerosol inhalation (0mg)	1.25 mg ADASUVE, single dose Staccato Loxapine	2.5 mg ADASUVE, single dose Staccato Loxapine	5 mg ADASUVE, single dose Staccato Loxapine	Total of all reporting groups
Overall Participants	39	43	43	43	168
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	39 100%	43 100%	43 100%	43 100%	168 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.2 (10.94)	41.7 (13.09)	38.5 (11.89)	42.3 (12.68)	41.1 (2.20)
Sex: Female, Male (Count of Participants)
Female	29 74.4%	38 88.4%	32 74.4%	35 81.4%	134 79.8%
Male	10 25.6%	5 11.6%	11 25.6%	8 18.6%	34 20.2%
Region of Enrollment (participants) [Number]
United States	39 100%	43 100%	43 100%	43 100%	168 100%

Outcome Measures

1. Primary Outcome

Title	Pain-relief Response (Pain Severity of NONE or MILD) at 2 Hours
Description	The primary efficacy endpoint was Pain-relief response as defined by the International Headache Society (Pain-IHS) as a pain severity of NONE or MILD. Intent to treat (ITT) with last observation carried forward (LOCF)
Time Frame	Baseline and 2 h post-dose

Outcome Measure Data

Analysis Population Description

ITT Population with LOCF

Arm/Group Title	Staccato Placebo	1.25 mg Staccato Loxapine	2.5 mg Staccato Loxapine	5 mg Staccato Loxapine
Arm/Group Description	Staccato Placebo, 0 mg Staccato Placebo: Placebo aerosol inhalation (0mg)	1.25 mg ADASUVE, single dose Staccato Loxapine	2.5 mg ADASUVE, single dose Staccato Loxapine	5 mg ADASUVE, single dose Staccato Loxapine
Measure Participants	39	43	43	43
Number [participants]	20 51.3%	29 67.4%	34 79.1%	33 76.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Staccato Placebo, 5 mg Staccato Loxapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0212
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Staccato Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0106
	Comments
	Method	Fisher Exact
	Comments

2. Secondary Outcome

Title	Pain-free at 2 Hours
Description	Pain-free (Pain-IHS) at the 2 hour time point
Time Frame	Baseline and 2 h post-dose

Outcome Measure Data

Analysis Population Description

ITT with LOCF Population

Arm/Group Title	Staccato Placebo	1.25 mg Staccato Loxapine	2.5 mg Staccato Loxapine	5 mg Staccato Loxapine
Arm/Group Description	Staccato Placebo, 0 mg Staccato Placebo: Placebo aerosol inhalation (0mg)	1.25 mg ADASUVE, single dose Staccato Loxapine	2.5 mg ADASUVE, single dose Staccato Loxapine	5 mg ADASUVE, single dose Staccato Loxapine
Measure Participants	39	43	43	43
Count of Participants [Participants]	3 7.7%	12 27.9%	13 30.2%	9 20.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Staccato Placebo, 2.5 mg Staccato Loxapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0123
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Staccato Placebo, 1.25 mg Staccato Loxapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0228
	Comments
	Method	Fisher Exact
	Comments

3. Other Pre-specified Outcome

Title	Responders, Sustained Freedom From Pain
Description	The percentages of patients with sustained freedom from pain (pain-free at 2 hours after dosing with no rescue medication and no recurrence of headache from 2 to 24 hours)
Time Frame	Baseline through 24 h post-dose

Outcome Measure Data

Analysis Population Description

ITT with LOCF Population

Arm/Group Title	Staccato Placebo	1.25 mg Staccato Loxapine	2.5 mg Staccato Loxapine	5 mg Staccato Loxapine
Arm/Group Description	Staccato Placebo, 0 mg Staccato Placebo: Placebo aerosol inhalation (0mg)	1.25 mg ADASUVE, single dose Staccato Loxapine	2.5 mg ADASUVE, single dose Staccato Loxapine	5 mg ADASUVE, single dose Staccato Loxapine
Measure Participants	39	43	43	43
Count of Participants [Participants]	3 7.7%	9 20.9%	11 25.6%	7 16.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Staccato Placebo, 2.5 mg Staccato Loxapine
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0409
	Comments
	Method	Fisher Exact
	Comments

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 at 9 pre-specified time points as well as whenever spontaneously reported by the subjects or study staff
Arm/Group Title	Staccato Placebo		1.25 mg Staccato Loxapine		2.5 mg Staccato Loxapine		5 mg Staccato Loxapine
Arm/Group Description	Staccato Placebo, 0 mg Staccato Placebo: Placebo aerosol inhalation (0mg)		1.25 mg ADASUVE, single dose Staccato Loxapine		2.5 mg ADASUVE, single dose Staccato Loxapine		5 mg ADASUVE, single dose Staccato Loxapine
All Cause Mortality
	Staccato Placebo		1.25 mg Staccato Loxapine		2.5 mg Staccato Loxapine		5 mg Staccato Loxapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/43 (0%)		0/43 (0%)		0/43 (0%)
Serious Adverse Events
	Staccato Placebo		1.25 mg Staccato Loxapine		2.5 mg Staccato Loxapine		5 mg Staccato Loxapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/43 (0%)		0/43 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Staccato Placebo		1.25 mg Staccato Loxapine		2.5 mg Staccato Loxapine		5 mg Staccato Loxapine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/39 (35.9%)		18/43 (41.9%)		21/43 (48.8%)		27/43 (62.8%)
Gastrointestinal disorders
Dry Mouth	2/39 (5.1%)	2	1/43 (2.3%)	1	2/43 (4.7%)	2	2/43 (4.7%)	2
Dysgeusia	5/39 (12.8%)	5	8/43 (18.6%)	8	10/43 (23.3%)	10	16/43 (37.2%)	16
Hypoaesthesia Oral	0/39 (0%)	0	1/43 (2.3%)	1	2/43 (4.7%)	2	1/43 (2.3%)	1
Oral Discomfort	1/39 (2.6%)	1	0/43 (0%)	0	1/43 (2.3%)	1	3/43 (7%)	3
General disorders
Fatigue	3/39 (7.7%)	3	0/43 (0%)	0	3/43 (7%)	3	6/43 (14%)	6
Nervous system disorders
Disturbance in Attention	0/39 (0%)	0	2/43 (4.7%)	2	0/43 (0%)	0	1/43 (2.3%)	1
Dizziness	2/39 (5.1%)	2	1/43 (2.3%)	1	3/43 (7%)	3	1/43 (2.3%)	1
Somnolence	5/39 (12.8%)	5	2/43 (4.7%)	2	10/43 (23.3%)	10	10/43 (23.3%)	10
Respiratory, thoracic and mediastinal disorders
Pharyngeal Hypoaesthesia	0/39 (0%)	0	0/43 (0%)	0	0/43 (0%)	0	3/43 (7%)	3
Throat Irritation	0/39 (0%)	0	3/43 (7%)	3	0/43 (0%)	0	0/43 (0%)	0
Vascular disorders
Hypotension	1/39 (2.6%)	1	0/43 (0%)	0	1/43 (2.3%)	1	2/43 (4.7%)	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.