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Efficacy and Safety of MAP0004, Orally Inhaled DHE in Treating Migraines With and Without Allodynia

Authors

  • Stewart J. Tepper MD,

    Corresponding author
    1. From the Neurological Institute, Cleveland Clinic Center for Headache and Pain, Cleveland, OH, USA (S.J. Tepper); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, M.H. Wang, and B. Hu); Houston Headache Clinic, Houston, TX, USA (N.T. Mathew); Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein).
      S.J. Tepper, Cleveland Clinic, Neurological Institute, Center for Headache and Pain, 9500 Euclid Ave, Cleveland, OH 44195-0002, USA, email: teppers@ccf.org
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  • Shashidhar H. Kori MD,

    1. From the Neurological Institute, Cleveland Clinic Center for Headache and Pain, Cleveland, OH, USA (S.J. Tepper); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, M.H. Wang, and B. Hu); Houston Headache Clinic, Houston, TX, USA (N.T. Mathew); Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein).
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  • Scott W. Borland MS,

    1. From the Neurological Institute, Cleveland Clinic Center for Headache and Pain, Cleveland, OH, USA (S.J. Tepper); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, M.H. Wang, and B. Hu); Houston Headache Clinic, Houston, TX, USA (N.T. Mathew); Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein).
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  • Min H. Wang PhD,

    1. From the Neurological Institute, Cleveland Clinic Center for Headache and Pain, Cleveland, OH, USA (S.J. Tepper); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, M.H. Wang, and B. Hu); Houston Headache Clinic, Houston, TX, USA (N.T. Mathew); Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein).
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  • Bin Hu MS,

    1. From the Neurological Institute, Cleveland Clinic Center for Headache and Pain, Cleveland, OH, USA (S.J. Tepper); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, M.H. Wang, and B. Hu); Houston Headache Clinic, Houston, TX, USA (N.T. Mathew); Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein).
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  • Ninan T. Mathew MD,

    1. From the Neurological Institute, Cleveland Clinic Center for Headache and Pain, Cleveland, OH, USA (S.J. Tepper); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, M.H. Wang, and B. Hu); Houston Headache Clinic, Houston, TX, USA (N.T. Mathew); Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein).
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  • Stephen D. Silberstein MD

    1. From the Neurological Institute, Cleveland Clinic Center for Headache and Pain, Cleveland, OH, USA (S.J. Tepper); MAP Pharmaceuticals, Mountain View, CA, USA (S.H. Kori, S.W. Borland, M.H. Wang, and B. Hu); Houston Headache Clinic, Houston, TX, USA (N.T. Mathew); Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA (S.D. Silberstein).
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  • Conflict of Interest: Dr. Tepper reports having received grants and research support from ATI, GlaxoSmithKline (GSK), MAP, Merck, NuPathe, and Zogenix; served as a consultant and/or on the advisory board for Allergan, GSK, Helsinn, MAP, Merck, Nautilus, NuPathe, and Zogenix; and served on the speakers' bureau for Allergan, GSK, Nautilus, Merck, and Zogenix. Dr. Kori, Mr. Borland, Dr. Wang, and Mrs. Hu are employees of MAP and own stock or stock options in MAP. Dr. Mathew reports having received grants or honoraria from GSK, Merck, Pfizer, Endo, and Forest; and serves as a consultant or on the advisory board for Allergan. 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.

  • Sources of funding: 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.J. Tepper, Cleveland Clinic, Neurological Institute, Center for Headache and Pain, 9500 Euclid Ave, Cleveland, OH 44195-0002, USA, email: teppers@ccf.org

Abstract

Background.— Central sensitization develops once migraine attacks become established and can be clinically detected by the development of cutaneous allodynia. The efficacy of triptans for migraine resolution has been shown to be markedly reduced when administered in patients with established cutaneous allodynia.

Objective.— The study aimed to evaluate the efficacy and safety of MAP0004, a novel, orally inhaled, form of dihydroergotamine, in patients with and without cutaneous allodynia at the time of treatment.

Methods.— This evaluation was a post hoc subanalysis of a randomized, double-blind, placebo-controlled, 2-arm, phase 3, multicenter study. The presence or absence of baseline cutaneous allodynia at the time of drug administration was based on the response to a standard questionnaire. Treatment efficacy at 2 hours posttreatment was compared in patients with and without baseline allodynia.

Results.— At the time of treatment, allodynia was present in 216 patients treated with MAP0004 and 202 patients treated with placebo. MAP0004 treatment efficacy was superior to placebo, as measured by 2-hour pain relief for patients with and without allodynia (P < .0001) and as measured by 2-hour pain freedom for patients with (P < .0001) and without (P < .0002) allodynia. No significant within-treatment differences after treatment with MAP0004 in patients with and without allodynia at baseline were observed. Patients were more likely to be allodynia-free after treatment with MAP0004 compared with placebo (73% vs 66%, P = .0013). Furthermore, treatment with MAP0004 prevented the development of allodynia in patients not experiencing allodynia at baseline (P = .0057). MAP0004 was generally well tolerated.

Conclusions.— This post hoc subanalysis shows that MAP0004 was similarly effective in patients whether or not allodynia was present at treatment baseline. Patients were also more likely to be allodynia-free following treatment of a migraine with MAP0004.

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