MAP0004, orally inhaled DHE: A randomized, controlled study in the acute treatment of migraine

Sheena K. Aurora, Stephen D. Silberstein, Shashidhar H. Kori, Stewart J. Tepper, Scott W. Borland, Min Wang, David William Dodick

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Objective. - To evaluate the efficacy and tolerability of MAP0004 compared with placebo for a single migraine in adult migraineurs: The FREEDOM-301 Study. Background. - Acute treatment of migraine remains a clinical challenge despite the availability of triptans and other agents. Injectable dihydroergotamine, although effective, is considered invasive and inconvenient, and intranasal dihydroergotamine is associated with inconsistent systemic dosage delivery. MAP0004 is an orally inhaled formulation of dihydroergotamine delivered to the systemic circulation. In a phase 2 study, MAP0004 provided significant early onset of pain relief (10 minutes, P < .05) and sustained pain relief for up to 48 hours with a favorable adverse event profile. Methods. - A phase 3, randomized, double-blind, placebo-controlled, parallel-group, single-attack, outpatient study of MAP0004, an inhaled dihydroergotamine was conducted at 102 sites in 903 adults with a history of episodic migraine. Patients were randomized (1:1) to receive MAP0004 (0.63 mg emitted dose; 1.0 mg nominal dose) or placebo, administered after onset of a migraine headache with moderate to severe pain. The co-primary endpoints were patient-assessed pain relief and absence of photophobia, phonophobia, and nausea at 2 hours after treatment. Results. - A total of 903 patients (450 active, 453 placebo) were randomized, and 792 (395 active, 397 placebo) experienced a qualifying migraine. MAP0004 was superior to placebo in all 4 co-primary endpoints: pain relief (58.7% vs 34.5%, P < .0001), phonophobia free (52.9% vs 33.8%, P < .0001), photophobia free (46.6% vs 27.2%, P < .0001), and nausea free (67.1% vs 58.7%, P = .0210). Additionally, significantly more patients were pain-free at 2 hours following treatment with MAP0004 than with placebo (28.4% vs 10.1%, P < .0001). MAP0004 was well tolerated; no drug-related serious adverse events occurred. Conclusions. - In this study, MAP0004 was effective and well tolerated for the acute treatment of migraine with or without aura, providing statistically significant pain relief and freedom from photophobia, phonophobia, and nausea in adults with migraine compared with placebo.

Original languageEnglish (US)
Pages (from-to)507-517
Number of pages11
JournalHeadache
Volume51
Issue number4
DOIs
StatePublished - Apr 2011

Fingerprint

Migraine Disorders
Placebos
Dihydroergotamine
Hyperacusis
Pain
Photophobia
Nausea
Therapeutics
Tryptamines
Migraine without Aura
Migraine with Aura
Outpatients
Injections
Pharmaceutical Preparations

Keywords

  • Clinical trial
  • Dihydroergotamine
  • MAP0004
  • Migraine
  • Oral inhalation
  • Sustained pain relief

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Aurora, S. K., Silberstein, S. D., Kori, S. H., Tepper, S. J., Borland, S. W., Wang, M., & Dodick, D. W. (2011). MAP0004, orally inhaled DHE: A randomized, controlled study in the acute treatment of migraine. Headache, 51(4), 507-517. https://doi.org/10.1111/j.1526-4610.2011.01869.x

MAP0004, orally inhaled DHE : A randomized, controlled study in the acute treatment of migraine. / Aurora, Sheena K.; Silberstein, Stephen D.; Kori, Shashidhar H.; Tepper, Stewart J.; Borland, Scott W.; Wang, Min; Dodick, David William.

In: Headache, Vol. 51, No. 4, 04.2011, p. 507-517.

Research output: Contribution to journalArticle

Aurora, SK, Silberstein, SD, Kori, SH, Tepper, SJ, Borland, SW, Wang, M & Dodick, DW 2011, 'MAP0004, orally inhaled DHE: A randomized, controlled study in the acute treatment of migraine', Headache, vol. 51, no. 4, pp. 507-517. https://doi.org/10.1111/j.1526-4610.2011.01869.x
Aurora SK, Silberstein SD, Kori SH, Tepper SJ, Borland SW, Wang M et al. MAP0004, orally inhaled DHE: A randomized, controlled study in the acute treatment of migraine. Headache. 2011 Apr;51(4):507-517. https://doi.org/10.1111/j.1526-4610.2011.01869.x
Aurora, Sheena K. ; Silberstein, Stephen D. ; Kori, Shashidhar H. ; Tepper, Stewart J. ; Borland, Scott W. ; Wang, Min ; Dodick, David William. / MAP0004, orally inhaled DHE : A randomized, controlled study in the acute treatment of migraine. In: Headache. 2011 ; Vol. 51, No. 4. pp. 507-517.
@article{174f010b080c4de9a43e83b0428480f1,
title = "MAP0004, orally inhaled DHE: A randomized, controlled study in the acute treatment of migraine",
abstract = "Objective. - To evaluate the efficacy and tolerability of MAP0004 compared with placebo for a single migraine in adult migraineurs: The FREEDOM-301 Study. Background. - Acute treatment of migraine remains a clinical challenge despite the availability of triptans and other agents. Injectable dihydroergotamine, although effective, is considered invasive and inconvenient, and intranasal dihydroergotamine is associated with inconsistent systemic dosage delivery. MAP0004 is an orally inhaled formulation of dihydroergotamine delivered to the systemic circulation. In a phase 2 study, MAP0004 provided significant early onset of pain relief (10 minutes, P < .05) and sustained pain relief for up to 48 hours with a favorable adverse event profile. Methods. - A phase 3, randomized, double-blind, placebo-controlled, parallel-group, single-attack, outpatient study of MAP0004, an inhaled dihydroergotamine was conducted at 102 sites in 903 adults with a history of episodic migraine. Patients were randomized (1:1) to receive MAP0004 (0.63 mg emitted dose; 1.0 mg nominal dose) or placebo, administered after onset of a migraine headache with moderate to severe pain. The co-primary endpoints were patient-assessed pain relief and absence of photophobia, phonophobia, and nausea at 2 hours after treatment. Results. - A total of 903 patients (450 active, 453 placebo) were randomized, and 792 (395 active, 397 placebo) experienced a qualifying migraine. MAP0004 was superior to placebo in all 4 co-primary endpoints: pain relief (58.7{\%} vs 34.5{\%}, P < .0001), phonophobia free (52.9{\%} vs 33.8{\%}, P < .0001), photophobia free (46.6{\%} vs 27.2{\%}, P < .0001), and nausea free (67.1{\%} vs 58.7{\%}, P = .0210). Additionally, significantly more patients were pain-free at 2 hours following treatment with MAP0004 than with placebo (28.4{\%} vs 10.1{\%}, P < .0001). MAP0004 was well tolerated; no drug-related serious adverse events occurred. Conclusions. - In this study, MAP0004 was effective and well tolerated for the acute treatment of migraine with or without aura, providing statistically significant pain relief and freedom from photophobia, phonophobia, and nausea in adults with migraine compared with placebo.",
keywords = "Clinical trial, Dihydroergotamine, MAP0004, Migraine, Oral inhalation, Sustained pain relief",
author = "Aurora, {Sheena K.} and Silberstein, {Stephen D.} and Kori, {Shashidhar H.} and Tepper, {Stewart J.} and Borland, {Scott W.} and Min Wang and Dodick, {David William}",
year = "2011",
month = "4",
doi = "10.1111/j.1526-4610.2011.01869.x",
language = "English (US)",
volume = "51",
pages = "507--517",
journal = "Headache",
issn = "0017-8748",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - MAP0004, orally inhaled DHE

T2 - A randomized, controlled study in the acute treatment of migraine

AU - Aurora, Sheena K.

AU - Silberstein, Stephen D.

AU - Kori, Shashidhar H.

AU - Tepper, Stewart J.

AU - Borland, Scott W.

AU - Wang, Min

AU - Dodick, David William

PY - 2011/4

Y1 - 2011/4

N2 - Objective. - To evaluate the efficacy and tolerability of MAP0004 compared with placebo for a single migraine in adult migraineurs: The FREEDOM-301 Study. Background. - Acute treatment of migraine remains a clinical challenge despite the availability of triptans and other agents. Injectable dihydroergotamine, although effective, is considered invasive and inconvenient, and intranasal dihydroergotamine is associated with inconsistent systemic dosage delivery. MAP0004 is an orally inhaled formulation of dihydroergotamine delivered to the systemic circulation. In a phase 2 study, MAP0004 provided significant early onset of pain relief (10 minutes, P < .05) and sustained pain relief for up to 48 hours with a favorable adverse event profile. Methods. - A phase 3, randomized, double-blind, placebo-controlled, parallel-group, single-attack, outpatient study of MAP0004, an inhaled dihydroergotamine was conducted at 102 sites in 903 adults with a history of episodic migraine. Patients were randomized (1:1) to receive MAP0004 (0.63 mg emitted dose; 1.0 mg nominal dose) or placebo, administered after onset of a migraine headache with moderate to severe pain. The co-primary endpoints were patient-assessed pain relief and absence of photophobia, phonophobia, and nausea at 2 hours after treatment. Results. - A total of 903 patients (450 active, 453 placebo) were randomized, and 792 (395 active, 397 placebo) experienced a qualifying migraine. MAP0004 was superior to placebo in all 4 co-primary endpoints: pain relief (58.7% vs 34.5%, P < .0001), phonophobia free (52.9% vs 33.8%, P < .0001), photophobia free (46.6% vs 27.2%, P < .0001), and nausea free (67.1% vs 58.7%, P = .0210). Additionally, significantly more patients were pain-free at 2 hours following treatment with MAP0004 than with placebo (28.4% vs 10.1%, P < .0001). MAP0004 was well tolerated; no drug-related serious adverse events occurred. Conclusions. - In this study, MAP0004 was effective and well tolerated for the acute treatment of migraine with or without aura, providing statistically significant pain relief and freedom from photophobia, phonophobia, and nausea in adults with migraine compared with placebo.

AB - Objective. - To evaluate the efficacy and tolerability of MAP0004 compared with placebo for a single migraine in adult migraineurs: The FREEDOM-301 Study. Background. - Acute treatment of migraine remains a clinical challenge despite the availability of triptans and other agents. Injectable dihydroergotamine, although effective, is considered invasive and inconvenient, and intranasal dihydroergotamine is associated with inconsistent systemic dosage delivery. MAP0004 is an orally inhaled formulation of dihydroergotamine delivered to the systemic circulation. In a phase 2 study, MAP0004 provided significant early onset of pain relief (10 minutes, P < .05) and sustained pain relief for up to 48 hours with a favorable adverse event profile. Methods. - A phase 3, randomized, double-blind, placebo-controlled, parallel-group, single-attack, outpatient study of MAP0004, an inhaled dihydroergotamine was conducted at 102 sites in 903 adults with a history of episodic migraine. Patients were randomized (1:1) to receive MAP0004 (0.63 mg emitted dose; 1.0 mg nominal dose) or placebo, administered after onset of a migraine headache with moderate to severe pain. The co-primary endpoints were patient-assessed pain relief and absence of photophobia, phonophobia, and nausea at 2 hours after treatment. Results. - A total of 903 patients (450 active, 453 placebo) were randomized, and 792 (395 active, 397 placebo) experienced a qualifying migraine. MAP0004 was superior to placebo in all 4 co-primary endpoints: pain relief (58.7% vs 34.5%, P < .0001), phonophobia free (52.9% vs 33.8%, P < .0001), photophobia free (46.6% vs 27.2%, P < .0001), and nausea free (67.1% vs 58.7%, P = .0210). Additionally, significantly more patients were pain-free at 2 hours following treatment with MAP0004 than with placebo (28.4% vs 10.1%, P < .0001). MAP0004 was well tolerated; no drug-related serious adverse events occurred. Conclusions. - In this study, MAP0004 was effective and well tolerated for the acute treatment of migraine with or without aura, providing statistically significant pain relief and freedom from photophobia, phonophobia, and nausea in adults with migraine compared with placebo.

KW - Clinical trial

KW - Dihydroergotamine

KW - MAP0004

KW - Migraine

KW - Oral inhalation

KW - Sustained pain relief

UR - http://www.scopus.com/inward/record.url?scp=79953688704&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79953688704&partnerID=8YFLogxK

U2 - 10.1111/j.1526-4610.2011.01869.x

DO - 10.1111/j.1526-4610.2011.01869.x

M3 - Article

C2 - 21457235

AN - SCOPUS:79953688704

VL - 51

SP - 507

EP - 517

JO - Headache

JF - Headache

SN - 0017-8748

IS - 4

ER -