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Randomized, Controlled Study of Telcagepant in Patients With Migraine and Coronary Artery Disease

Authors

  • Tony W. Ho MD,

    Corresponding author
    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Andrew P. Ho MD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Bernard R. Chaitman MD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Constance Johnson MD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Ninan T. Mathew MD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • James Kost PhD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Xiaoyin Fan PhD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Sheena K. Aurora MD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Jan L. Brandes MD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Kaiyin Fei MD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Louise Beebe MSN,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Christopher Lines PhD,

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Mitchell W. Krucoff MD

    1. From the Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA (T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines); St. Louis University School of Medicine, St. Louis, MO, USA (B.R. Chaitman); Headache Care Center, Clarksville, TN, USA (C. Johnson); Houston Headache Clinic-Neurology, Houston, TX, USA (N.T. Mathew); Swedish Headache Center, Seattle, WA, USA (S.K. Aurora); Vanderbilt University School of Medicine, Nashville, TN, USA (J.L. Brandes); Duke University Medical Center, Durham, NC, USA (M.W. Krucoff).
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  • Trial Registration: ClinicalTrials.gov NCT00662818

  • Conflict of interest Statement: This study was funded by Merck Research Laboratories. T.W. Ho, A.P. Ho, J. Kost, X. Fan, K. Fei, L. Beebe, and C. Lines are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., and own stock/stock options in Merck. B.R. Chaitman, C. Johnson, N.T. Mathew, and M.W. Krucoff have received research funding and consulting fees from Merck. S.K. Aurora and J.L. Brandes have received research funding from Merck.

  • Study investigators: Belgium: Jean Jacquy, Paul Louis; Brazil: Lisellote Barea; Chile: Sergio Gloger; Columbia: Basilio Vagner, Nhora Patricia Ruiz, Michel Volcy; Costa Rica: Roberto Vargas; India: Shamsher Dwivedee; Italy: Paolo Martelletti, Maria Adele Giamberardino, Giuseppe Lembo; Mexico: Sarug Reyes, Rosalia Vazquez Alfaro; Russian Federation: Elena Filatova, Gusal R. Tabeeva, Yuri M. Nemchenko; Switzerland: Peter Sandor, Reto Agosti; Taiwan: Shuu-Jiun Wang, Po-Jen Wang; United States: Sheena K. Aurora, Jan L. Brandes, Carol A. Foster, Constance Johnson, Sylvia M. Lucas, Herbert Markley, Neil Pugach, Hemanth T. Rao, Joel R. Saper, Timothy R. Smith, Tarvez Tucker, Alberto B. Vasquez, Barbara Vogler, Kenneth Carnes, Peter J. McAllister, Paul J. Markovitz, Anthony J. Bartkowiak, Rafael Chiong, Clinton N. Corder, Wilfred McKenzie, Frederick G. Freitag, Richard E. Martinez, Ninan T. Mathew, Carol Tanner-St. James, Aliuska Alvarez, John E. Castaldo, Robert A. Riesenberg, Sara Sacco, Marshall C. Freeman, Jeffrey D. Gould, Richard Giusti, Kishor N. Vora, Steven Gelfand, Steve H. Choi, and Marina Raikhel.

  • The following were members of the Independent Safety Monitoring Board: Guy McKhann, Carl Dahlof, Chris Cannon, Michael Eliasziw, and Nabih Ramadan.

T.W. Ho, Merck Sharp & Dohme Corp., UG 4C-18, PO Box 1000, North Wales, PA 19454-1099, USA, email: tony.ho@merck.com

Abstract

Objective.— To evaluate the efficacy of telcagepant in patients with migraine and coronary artery disease.

Background.— Calcitonin gene-related peptide receptor antagonists, such as telcagepant, may be useful for acute migraine treatment in patients with cardiovascular disease, a population for whom triptans are contraindicated.

Methods.— Randomized, double-blind, two-period (6 weeks per period) crossover study in patients with stable coronary artery disease and migraine. Patients were randomized 1:1 to either: (1) Period 1: telcagepant (280-mg tablet/300-mg capsule), Period 2: acetaminophen (1000-mg); or (2) Period 1: placebo for attack 1 then acetaminophen for subsequent attacks, Period 2: telcagepant. Patients could treat up to 12 migraine attacks per period to assess the tolerability of telcagepant. The primary efficacy analysis evaluated telcagepant vs placebo on 2-hour pain freedom during the first attack of Period 1.

Results.— One hundred and sixty-five of the planned 400 patients were enrolled, and 114 took at least one dose of treatment. Telcagepant was not statistically different from placebo for 2-hour pain freedom (25.0% vs 18.9%, odds ratio = 1.62 [95% confidence interval: 0.62, 4.25]). The median number of attacks treated per period was 3. No cardiovascular thrombotic adverse events occurred within 14 days of dosing.

Conclusion.— The study was underpowered due to enrollment difficulties and did not demonstrate a significant efficacy difference between telcagepant and placebo for the treatment of a migraine attack in patients with stable coronary artery disease. Telcagepant was generally well tolerated for acute intermittent migraine treatment in these patients.

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