Long-Term Tolerability of Telcagepant for Acute Treatment of Migraine in a Randomized Trial

Authors

  • Kathryn M. Connor MD,

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Sheena K. Aurora MD,

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Tom Loeys PhD,

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Messoud Ashina MD,

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Christopher Jones BA,

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Hilde Giezek MSc,

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Rachid Massaad PhD,

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Angela Williams-Diaz BS,

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Christopher Lines PhD,

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Tony W. Ho MD

    1. From Merck, North Wales, PA, USA (K.M. Connor, C. Jones, A. Williams-Diaz, C. Lines, and T.W. Ho); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Merck Sharp & Dohme, Brussels, Belgium (T. Loeys, H. Giezek, and R. Massaad); Danish Headache Center and Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark (M. Ashina).
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  • Disclosure:

  • This study was funded by Merck Research Laboratories. The funding organization was involved in the following: design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript.

  • Kathryn M. Connor, Tom Loeys, Christopher Jones, Hilde Giezek, Rachid Massaad, Angela Williams-Diaz, Christopher Lines, and Tony W. Ho are employees of Merck and own stock/stock options in Merck.

  • Sheena K. Aurora has received grant and research support from Advanced Bionics, Alexza, Allergan, GlaxoSmithKline, MAP Pharmaceuticals, Merck, Ortho-McNeil, Neuralieve, and Takeda; has served as a consultant for Ortho-McNeil Pharmaceutical, Merck, GlaxoSmithKline, Allergan, and Neuralieve; and has received honoraria from Merck, GlaxoSmithKline, NuPathe, and Ortho-McNeil Pharmaceutical.

  • Messoud Ashina has received grant support and honoraria for lecturing from Merck, and honoraria for lecturing from Pfizer, GlaxoSmithKline, and AstraZeneca, and he is a consultant and/or scientific adviser for Merck and BTG International.

  • All authors are responsible for the work described in this paper. All authors were involved in at least one of the following: conception, design, acquisition, analysis, statistical analysis, interpretation of data and drafting the manuscript and/or revising the manuscript for important intellectual content. All authors provided final approval of the version to be published.

T. Ho, Merck, UG 4C-18, PO Box 1000, North Wales, PA 19454-1099, USA.

Abstract

(Headache 2011;51:73-84)

Objective.— To evaluate the long-term tolerability of telcagepant for acute treatment of intermittent migraine attacks.

Background.— Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine.

Methods.— Migraine patients were randomized 2:1 to double-blind treatment with telcagepant 280/300 mg or rizatriptan 10 mg for an acute mild, moderate, or severe migraine. Patients could administer a second dose within 2-24 hours for nonresponse or migraine recurrence. Patients could treat up to 8 attacks per month for up to 18 months. Safety assessments included spontaneous reports of adverse events and collection of vital signs, electrocardiograms, and laboratory assessments. The primary endpoint was the percentage of patients with ≥1 triptan-related adverse events in the 14-day period post dose.

Results.— Of 1068 patients randomized, 641 (90%) patients treated ≥1 attack with telcagepant and 313 (88%) treated ≥1 attack with rizatriptan. A total of 19,820 attacks were treated with telcagepant (mean per patient = 31) and 10,981 with rizatriptan (mean per patient = 35). Fewer triptan-related adverse events (difference: −6.2%; 95% CI −10.4, −2.6; P < .001) and drug-related adverse events (difference: −15.6%; 95% CI −22.2, −9.0) were reported for telcagepant vs rizatriptan. The most common adverse events appeared to have generally similar incidence proportions between the treatment groups. Those with an incidence >5% in the telcagepant group were dry mouth (9.7%, rizatriptan = 13.7%), somnolence (9.2%, rizatriptan = 16.6%), dizziness (8.9%, rizatriptan = 10.2%), and nausea (9.0%, rizatriptan = 6.4%).

Conclusions.— Telcagepant was generally well tolerated when administered for the acute intermittent treatment of migraine for up to 18 months. The incidences of triptan-related and drug-related adverse events favored telcagepant over rizatriptan.

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