Migraine Disorders
Conditions
Keywords
Migraine
Brief summary
This is a randomized, double blind, placebo controlled, parallel group study of MAP0004 in adult migraineurs. Subjects will self administer study drug in the outpatient setting.
Interventions
DRUGMAP0004
MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks. Placebo treated patients will receive MAP0004 1.0mg inhaled to treat qualifying migraines for up to 52 weeks only.
DRUGPlacebo
Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks.
Sponsors
MAP Pharmaceuticals, Inc., a wholly owned subsidiary of Allergan
Allergan
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
No
Inclusion criteria
Major Inclusion Criteria: * Male or female between 18 and 65 years of age. * History of episodic, acute migraine (with or without aura) with onset prior to 50 Major
Exclusion criteria
* Known allergy or sensitivity or contraindication to study drugs or their formulations * History of chronic pulmonary disease, coronary artery disease (CAD), liver disease, kidney disease, seizures, stroke, or major psychiatric condition. * Any condition that, in the opinion of the Investigator, would make the subject unsuitable for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Nausea Free at 2 Hours From Time of First Dose | 2 hours from time of first dose | Nausea free was defined as a rating of none (score 0) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours post-dose. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities |
| Number of Subjects With Pain Relief at 2 Hours From Time of First Dose | 2 hours from time of first dose | Pain relief at 2 hours was defined as change in rating from severe or moderate (score 3 or 2) to a rating of none or mild (score 0 or 1) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities |
| Number of Subjects Photophobia Free at 2 Hours From Time of First Dose | 2 hours from time of first dose | Photophobia free at 2 hours was defined as a rating of none (score 0) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities |
| Number of Subjects Phonophobia Free at 2 Hours From Time of First Dose | 2 hours from time of first dose | Phonophobia free at 2 hours was defined as a rating of none (score 0) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Sustained Pain Relief From 2 to 24 Hours | From 2 to 24 hours from time of first dose | Sustained Pain Relief was defined as a rating of none or mild (score 0 or 1) at the 2-hour time point that was maintained during the 2-24 hour post-dose period and no use of rescue medication from the time of first dose to 24 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities |
| Number of Subjects Whose Time to Pain Relief Occurred Within 2 Hours | 2 hours from the first dose | The number of subjects who reported pain relief (score of 0 or 1) at any time within the 2 hours following the time of first dose and who did not use rescue medication on or prior to this point. Subjects who did not reach pain relief by the end of the time period were not included. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities |
| Number of Subjects With Pain Relief at 4 Hours | 4 hours from time of first dose | Pain Relief at 4 hours was defined as a change in rating from severe or moderate (score 3 or 2) to none or mild (score 0 or 1) at the 4-hour time point and no use of rescue medication from the time of first dose to 4 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities |
| Number of Subjects With Pain Relief at 10 Minutes | 2 hours from time of first dose | Pain Relief at 10 minutes was defined as a change in rating from severe or moderate (score 3 or 2) to none or mild (score 0 or 1) at the 10 minute time point and no use of rescue medication from the time of first dose to 2 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities |
Countries
United States
Participant flow
Pre-assignment details
This study included a Double-blind period for 8 weeks followed by an open-label period that lasted an additional 52 weeks. All patients participating in the open-label period received MAP0004.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat a qualifying migraine for up to an additional 52 weeks. | 397 |
| MAP0004 MAP0004 1.0mg inhaled to treat a qualifying migraine up to 8 weeks followed by MAP0004 1.0mg inhaled to treat qualifying migraines for up to an additional 52 weeks. | 397 |
| Total | 794 |
Baseline characteristics
| Characteristic | Placebo | MAP0004 | Total |
|---|---|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 11.67 | 40.5 years STANDARD_DEVIATION 11.3 | 40.1 years STANDARD_DEVIATION 11.49 |
| Sex: Female, Male Female | 362 Participants | 365 Participants | 727 Participants |
| Sex: Female, Male Male | 35 Participants | 32 Participants | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 60 / 404 | 86 / 410 | 454 / 638 |
| serious Total, serious adverse events | 0 / 404 | 0 / 410 | 14 / 638 |
Outcome results
Primary
Number of Subjects Nausea Free at 2 Hours From Time of First Dose
Nausea free was defined as a rating of none (score 0) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours post-dose. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities
Time frame: 2 hours from time of first dose
Population: mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects Nausea Free at 2 Hours From Time of First Dose | 234 participants |
| MAP0004 | Number of Subjects Nausea Free at 2 Hours From Time of First Dose | 266 participants |
Primary
Number of Subjects Phonophobia Free at 2 Hours From Time of First Dose
Phonophobia free at 2 hours was defined as a rating of none (score 0) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities
Time frame: 2 hours from time of first dose
Population: mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects Phonophobia Free at 2 Hours From Time of First Dose | 133 participants |
| MAP0004 | Number of Subjects Phonophobia Free at 2 Hours From Time of First Dose | 208 participants |
Primary
Number of Subjects Photophobia Free at 2 Hours From Time of First Dose
Photophobia free at 2 hours was defined as a rating of none (score 0) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities
Time frame: 2 hours from time of first dose
Population: mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects Photophobia Free at 2 Hours From Time of First Dose | 107 participants |
| MAP0004 | Number of Subjects Photophobia Free at 2 Hours From Time of First Dose | 182 participants |
Primary
Number of Subjects With Pain Relief at 2 Hours From Time of First Dose
Pain relief at 2 hours was defined as change in rating from severe or moderate (score 3 or 2) to a rating of none or mild (score 0 or 1) at the 2-hour time point and no usage of rescue medications from the time of first dose to 2 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities
Time frame: 2 hours from time of first dose
Population: mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects With Pain Relief at 2 Hours From Time of First Dose | 136 participants |
| MAP0004 | Number of Subjects With Pain Relief at 2 Hours From Time of First Dose | 231 participants |
Secondary
Number of Subjects Whose Time to Pain Relief Occurred Within 2 Hours
The number of subjects who reported pain relief (score of 0 or 1) at any time within the 2 hours following the time of first dose and who did not use rescue medication on or prior to this point. Subjects who did not reach pain relief by the end of the time period were not included. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities
Time frame: 2 hours from the first dose
Population: mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects Whose Time to Pain Relief Occurred Within 2 Hours | 156 participants |
| MAP0004 | Number of Subjects Whose Time to Pain Relief Occurred Within 2 Hours | 244 participants |
Secondary
Number of Subjects With Pain Relief at 10 Minutes
Pain Relief at 10 minutes was defined as a change in rating from severe or moderate (score 3 or 2) to none or mild (score 0 or 1) at the 10 minute time point and no use of rescue medication from the time of first dose to 2 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities
Time frame: 2 hours from time of first dose
Population: mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects With Pain Relief at 10 Minutes | 30 participants |
| MAP0004 | Number of Subjects With Pain Relief at 10 Minutes | 37 participants |
Secondary
Number of Subjects With Pain Relief at 4 Hours
Pain Relief at 4 hours was defined as a change in rating from severe or moderate (score 3 or 2) to none or mild (score 0 or 1) at the 4-hour time point and no use of rescue medication from the time of first dose to 4 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities
Time frame: 4 hours from time of first dose
Population: mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects With Pain Relief at 4 Hours | 145 participants |
| MAP0004 | Number of Subjects With Pain Relief at 4 Hours | 254 participants |
Secondary
Number of Subjects With Sustained Pain Relief From 2 to 24 Hours
Sustained Pain Relief was defined as a rating of none or mild (score 0 or 1) at the 2-hour time point that was maintained during the 2-24 hour post-dose period and no use of rescue medication from the time of first dose to 24 hours. The 4-point scale from the International Headache Society was used: 0 = none; 1 = mild symptom, not interfering with normal daily activities; 2 = moderate symptom, causing some restriction to normal activities; 3 = severe, leading to inability to perform daily activities
Time frame: From 2 to 24 hours from time of first dose
Population: mITT population was defined as all randomized subjects who reported a qualifying migraine and received at least one dose of study treatment, and had at least one post-treatment efficacy evaluation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Subjects With Sustained Pain Relief From 2 to 24 Hours | 76 participants |
| MAP0004 | Number of Subjects With Sustained Pain Relief From 2 to 24 Hours | 166 participants |