MAP0004, Orally Inhaled DHE: A Randomized, Controlled Study in the Acute Treatment of Migraine

Authors

  • Sheena K. Aurora MD,

    1. From Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, and M. Wang); Cleveland Clinic, Neurological Center for Pain, Cleveland, OH, USA (S.J. Tepper); Mayo Clinic, Scottsdale, AZ, USA (D.W. Dodick).
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  • Stephen D. Silberstein MD,

    1. From Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, and M. Wang); Cleveland Clinic, Neurological Center for Pain, Cleveland, OH, USA (S.J. Tepper); Mayo Clinic, Scottsdale, AZ, USA (D.W. Dodick).
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  • Shashidhar H. Kori MD,

    1. From Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, and M. Wang); Cleveland Clinic, Neurological Center for Pain, Cleveland, OH, USA (S.J. Tepper); Mayo Clinic, Scottsdale, AZ, USA (D.W. Dodick).
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  • Stewart J. Tepper MD,

    1. From Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, and M. Wang); Cleveland Clinic, Neurological Center for Pain, Cleveland, OH, USA (S.J. Tepper); Mayo Clinic, Scottsdale, AZ, USA (D.W. Dodick).
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  • Scott W. Borland MS,

    1. From Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, and M. Wang); Cleveland Clinic, Neurological Center for Pain, Cleveland, OH, USA (S.J. Tepper); Mayo Clinic, Scottsdale, AZ, USA (D.W. Dodick).
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  • Min Wang PhD,

    1. From Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, and M. Wang); Cleveland Clinic, Neurological Center for Pain, Cleveland, OH, USA (S.J. Tepper); Mayo Clinic, Scottsdale, AZ, USA (D.W. Dodick).
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  • David W. Dodick MD

    1. From Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, and M. Wang); Cleveland Clinic, Neurological Center for Pain, Cleveland, OH, USA (S.J. Tepper); Mayo Clinic, Scottsdale, AZ, USA (D.W. Dodick).
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  • Conflict of Interest: Dr. Kori, Dr. Wang, and Mr. Borland are employees of MAP and own stock or stock options in MAP. Dr. Aurora reports having received grants/honoraria from or serving as a consultant or on the advisory board of Advanced Bionics, Alexza, Allergan, Capnia, GlaxoSmithKline, Kowa, MAP, Merck, Ortho-McNeil, Neuralieve, NuPathe, and Takeda. Dr. Silberstein reports having received grants or honoraria from Advanced NeuroModulation Systems, AGA, Allergan, Boston Scientific, Capnia, Coherex, Endo, GlaxoSmithKline, Lilly, MAP, Medtronic, Merck, NuPathe, and Valeant. Dr. Tepper reports having received grants and research support from ATI, GlaxoSmithKline, MAP, and Merck; serving as a consultant and on the advisory board for GSK, MAP, Merck, NuPathe, and Zogenix; and serving on the speakers bureau for GlaxoSmithKline, Valeant, and Merck. Dr. Dodick reports having received honoraria from Allergan, Merck, Neuralieve, Coherex, Kowa, Minster, NeurAxon, H. Lundbeck, Endo, Pfizer, Eli Lilly, Boston Scientific, Novartis, and MAP in addition to being a consultant to and on the advisory board of these pharmaceutical companies. He also reports having received research funding from Advanced Neurostimulation Systems and Medtronic.

  • Financial Statement: Role of the study sponsor: This research was funded by MAP Pharmaceuticals, Inc. MAP Pharmaceuticals provided financial and material support, monitoring, data collection and management, and data analysis to the authors and study investigators.

  • Clinical Trial Registration: The FREEDOM-301 study was registered at ClinicalTrials.gov (NCT00623636).

S.K. Aurora, Swedish Pain and Headache Center, 1101 Madison Street, Suite 200, Seattle, WA 98104, USA.

Abstract

(Headache 2011;51:507-517)

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.

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