Migraine
Conditions
Keywords
Staccato® Loxapine, Migraine
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.
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.
Interventions
DRUGStaccato Loxapine
DRUGStaccato Placebo
Placebo aerosol inhalation (0mg)
Sponsors
Alexza Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Pain-free at 2 Hours | Baseline and 2 h post-dose | Pain-free (Pain-IHS) at the 2 hour time point |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Staccato Placebo Staccato Placebo, 0 mg
Staccato Placebo: Placebo aerosol inhalation (0mg) | 39 |
| 1.25 mg Staccato Loxapine 1.25 mg ADASUVE, single dose
Staccato Loxapine | 43 |
| 2.5 mg Staccato Loxapine 2.5 mg ADASUVE, single dose
Staccato Loxapine | 43 |
| 5 mg Staccato Loxapine 5 mg ADASUVE, single dose
Staccato Loxapine | 43 |
| Total | 168 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | 1.25 mg Staccato Loxapine | 2.5 mg Staccato Loxapine | Staccato Placebo | 5 mg Staccato Loxapine | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 43 Participants | 43 Participants | 39 Participants | 43 Participants | 168 Participants |
| Age, Continuous | 41.7 years STANDARD_DEVIATION 13.09 | 38.5 years STANDARD_DEVIATION 11.89 | 42.2 years STANDARD_DEVIATION 10.94 | 42.3 years STANDARD_DEVIATION 12.68 | 41.1 years STANDARD_DEVIATION 2.2 |
| Region of Enrollment United States | 43 participants | 43 participants | 39 participants | 43 participants | 168 participants |
| Sex: Female, Male Female | 38 Participants | 32 Participants | 29 Participants | 35 Participants | 134 Participants |
| Sex: Female, Male Male | 5 Participants | 11 Participants | 10 Participants | 8 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 39 | 0 / 43 | 0 / 43 | 0 / 43 |
| other Total, other adverse events | 14 / 39 | 18 / 43 | 21 / 43 | 27 / 43 |
| serious Total, serious adverse events | 0 / 39 | 0 / 43 | 0 / 43 | 0 / 43 |
Outcome results
Primary
Pain-relief Response (Pain Severity of NONE or MILD) at 2 Hours
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
Population: ITT Population with LOCF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Staccato Placebo | Pain-relief Response (Pain Severity of NONE or MILD) at 2 Hours | 20 participants |
| 1.25 mg Staccato Loxapine | Pain-relief Response (Pain Severity of NONE or MILD) at 2 Hours | 29 participants |
| 2.5 mg Staccato Loxapine | Pain-relief Response (Pain Severity of NONE or MILD) at 2 Hours | 34 participants |
| 5 mg Staccato Loxapine | Pain-relief Response (Pain Severity of NONE or MILD) at 2 Hours | 33 participants |
p-value: 0.0212Fisher Exact
p-value: 0.0106Fisher Exact
Secondary
Pain-free at 2 Hours
Pain-free (Pain-IHS) at the 2 hour time point
Time frame: Baseline and 2 h post-dose
Population: ITT with LOCF Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staccato Placebo | Pain-free at 2 Hours | 3 Participants |
| 1.25 mg Staccato Loxapine | Pain-free at 2 Hours | 12 Participants |
| 2.5 mg Staccato Loxapine | Pain-free at 2 Hours | 13 Participants |
| 5 mg Staccato Loxapine | Pain-free at 2 Hours | 9 Participants |
p-value: 0.0123Fisher Exact
p-value: 0.0228Fisher Exact
Other Pre-specified
Responders, Sustained Freedom From Pain
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
Population: ITT with LOCF Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Staccato Placebo | Responders, Sustained Freedom From Pain | 3 Participants |
| 1.25 mg Staccato Loxapine | Responders, Sustained Freedom From Pain | 9 Participants |
| 2.5 mg Staccato Loxapine | Responders, Sustained Freedom From Pain | 11 Participants |
| 5 mg Staccato Loxapine | Responders, Sustained Freedom From Pain | 7 Participants |
p-value: 0.0409Fisher Exact