Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
MAP0004 · 5 trials · 3 indications
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
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
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
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
The corrected QT interval, individualized (QTcI) is a measurement of the electrical impulses through the largest part of the heart muscle individualized for subject pre-dose values. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.
The corrected QT interval, individualized (QTcI) is a measurement of the electrical impulses through the largest part of the heart muscle individualized for subject pre-dose values. A negative change is a shortening of the QTc interval, a positive change is a lengthening of the QTc interval.
The maximum concentration (Cmax) is the highest concentration of a drug measured in the plasma. Plasma is the clear portion of the blood. The Cmax of Dihydroergotamine is reported in picograms per milliliter (pg/ml).
The AUC(0-48) is the area under the plot of plasma concentration of drug against time after drug administration. Dihydroergotamine AUC(0-48) is reported in picograms times hour per milliliter (pg\*h/ml).
AUC(0-2hrs) (Area Under the Curve, time 0-2 hours post-1st dose) in PASP millimeters of mercury times minutes (mmHg\*min). PASP is the highest pressure exerted on the walls of the pulmonary artery.
The maximum concentration (Cmax) is the highest concentration of a drug measured in the plasma. Plasma is the clear portion of the blood. The Cmax of Dihydroergotamine is reported in picograms per milliliter (pg/ml).
The AUC(0-48) is the area under the plot of plasma concentration of drug against time after drug administration. Dihydroergotamine AUC(0-48) is reported in picograms times hour per milliliter (pg\*h/ml).
| Arm | Type | Description |
|---|---|---|
| MAP0004 | EXPERIMENTAL | 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 | OTHER | Placebo 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 52 weeks. |
| Treatment A, then Treatment B, then Treatment C | OTHER | There was 48 hour wash-out between treatment visits. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 2. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 3. Treatment C = inhaler placebo and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing. |
| Treatment A, then Treatment C, then Treatment B | OTHER | There was 48 hour wash-out between treatment visits. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 2. Treatment C = inhaler placebo and placebo capsules at Visit 3. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing. |
| Treatment B, then Treatment A, then Treatment C | OTHER | There was 48 hour wash-out between treatment visits. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 2. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 3. Treatment C = inhaler placebo and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing. |
| Treatment B, then Treatment C, then Treatment A | OTHER | There was 48 hour wash-out between treatment visits. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 2. Treatment C = inhaler placebo and placebo capsules at Visit 3. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 4. Tablets were orally administered after oral inhalation dosing. |
| Treatment C, then Treatment A, then Treatment B | OTHER | There was 48 hour wash-out between treatment visits. Treatment C = inhaler placebo and placebo capsules at Visit 2. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 3. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 4. Tablets were orally administered after oral inhalation dosing. |
| Treatment C, then Treatment B, then Treatment A | OTHER | There was 48 hour wash-out between treatment visits. Treatment C = inhaler placebo and placebo capsules at Visit 2. Treatment B = MAP0004 3.0mg (via inhalation) and placebo capsules at Visit 3. Treatment A = inhaler placebo and moxifloxacin 400mg encapsulated tablet at Visit 4. Tablets were orally administered after oral inhalation dosing. |
| All subjects | OTHER | Subjects received MAP0004 on Day 1 of Visit 2, Ketoconazole on Days 3 through 6 of Visit 2, and MAP0004 again on Day 6 of Visit 2. Subjects then returned for Visit 3, 7-11 days from the end of Visit 2. At Visit 3 subjects received 1.0 mg IV DHE (Intravenous Dihydroergotamine Mesylate). |
| IV DHE then MAP0004 | OTHER | Smokers and non-smokers received Intravenous Dihydroergotamine Mesylate (IV DHE) at Visit 2 followed by MAP0004 7-11 days later at Visit 3. |
| MAP0004 then IV DHE | OTHER | Smokers and non-smokers received MAP0004 at Visit 2 followed by Intravenous Dihydroergotamine Mesylate (IV DHE) 7-11 days later at Visit 3. |
| Name | Type | Description |
|---|---|---|
| MAP0004 | DRUG | 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. |
| Placebo | DRUG | Placebo 1.0mg inhaled to treat a qualifying migraine up to 8 weeks. |
| Inhaler Placebo | DRUG | Placebo for Inhaler administered in Treatments A and C |
| Moxifloxacin | DRUG | 400mg encapsulated tablet administered in Treatment A as per protocol |
| Placebo Capsule | DRUG | Placebo for Moxifloxacin administered in Treatment B and Treatment C |
| IV DHE | DRUG | IV DHE (Intravenous Dihydroergotamine Mesylate) administered at Visit 3 |
| Ketoconazole | DRUG | Ketoconazole 400 mg administered once a day on days 3-6 of Visit 2 |
| IV Placebo (Saline) | DRUG | IV Placebo (Saline) administered in Treatment B and Treatment C as per protocol |
| Placebo Inhaler | DRUG | Orally inhaled Placebo administered in Treatment A and Treatment C as per protocol. |
| IV Dihydroergotamine Mesylate (DHE) | DRUG | IV DHE administered in Treatment A as per protocol |
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 pul...
MAP0004 is an investigational small molecule being developed by AbbVie Inc. for the treatment of migraine disorders. It is also studied in healthy subjects for pharmacodynamic, pharmacokinetic, and safety evaluations. The drug is delivered via oral inhalation and contains dihydroergotamine mesylate (DHE).
MAP0004 contains dihydroergotamine mesylate (DHE), which is an ergot alkaloid that acts as an agonist at serotonin (5-HT) receptors, including 5-HT1B and 5-HT1D. This mechanism is thought to constrict cranial blood vessels and inhibit neurogenic inflammation, which may help relieve migraine symptoms.
MAP0004 is being developed by AbbVie Inc., a biopharmaceutical company traded on the New York Stock Exchange under the ticker symbol ABBV. The drug is an orally inhaled formulation of dihydroergotamine mesylate (DHE) intended for the treatment of migraine.
MAP0004 has completed Phase 1 and Phase 3 clinical trials. The Phase 3 study (NCT00623636) evaluated the drug in adult migraineurs, while Phase 1 studies assessed its effects on pulmonary arterial pressure, QT intervals, and pharmacokinetics when co-administered with ketoconazole. All trials are completed, and the drug remains investigational.
MAP0004 has been studied in three completed clinical trials. NCT00623636 was a Phase 3 study in 902 adult migraineurs. NCT01089062 was a Phase 1 pharmacodynamic study in 24 healthy subjects. NCT01191723 was a Phase 1 QT interval study in 54 healthy subjects. NCT01468558 was a Phase 1 pharmacokinetics study in 24 healthy subjects.
MAP0004 is an orally inhaled formulation of dihydroergotamine mesylate (DHE), a well-known ergot alkaloid used for migraine. While MAP0004 contains DHE as its active ingredient, it is a distinct drug product with a unique route of administration compared to other DHE formulations.