Effect of Telcagepant on Spontaneous Ischemia in Cardiovascular Patients in a Randomized Study

Authors

  • Martin O. Behm MD,

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • Rebecca L. Blanchard PhD,

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • M. Gail Murphy MD,

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • John S. Palcza MS,

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • Dawn E. Harris BSN,

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • Kristin L. Butterfield MS,

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • William B. Smith MD,

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • Richard A. Preston MD,

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • Jeffrey A. Chodakewitz MD,

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • Mitchell W. Krucoff MD

    1. From Merck & Co., Inc., North Wales, PA, USA (M.O. Behm, R.L. Blanchard, M. Gail Murphy, J.S. Palcza, D.E. Harris, K.L. Butterfield, and J.A. Chodakewitz); NOCCR, University of Tennessee Medical Center, Knoxville, TN, USA (W.B. Smith); Clinical Pharmacology, University of Miami, Miami, FL, USA (R.A. Preston); Cardiology Division, Duke University Medical Center/Duke Clinical Research Institute, Durham, NC, USA (M.W. Krucoff).
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  • Financial support: This study was funded by Merck & Co., Inc.

  • Conflict of Interest: Martin O. Behm, Rebecca L. Blanchard, M. Gail Murphy, John S. Palcza, Dawn E. Harris, Kristin L. Butterfield, and Jeffrey A. Chodakewitz are employees of Merck and own stock/stock options in Merck. William B. Smith has received research funding from Merck. Richard A. Preston has received research funding from Merck. Mitchell W. Krucoff has received research funding and consultancy fees from Merck.

M.O. Behm, Clinical Research, Merck & Co., Inc., PO Box 1000, Upper Gwynedd, PA 19454, USA. Email: martin_behm@merck.com

Abstract

(Headache 2011;51:954-960)

Objective.— The primary purpose of the study was to explore the safety and tolerability of telcagepant in patients with stable coronary artery disease.

Background.— Triptans are effective acute anti-migraine drugs whose vasoconstrictive effects limit their use in patients at risk for adverse cardiovascular events. Telcagepant, a calcitonin gene-related peptide receptor antagonist, is being developed for the acute treatment of migraine. Antagonism of calcitonin gene-related peptide, which does not appear to cause vasoconstriction, may allow for treatment of migraine in patients with coronary artery disease.

Methods.— In this randomized, double-blind, placebo-controlled, crossover study, patients with documented stable coronary artery disease were assigned to 1 of 2 treatment sequences: telcagepant then placebo, or placebo then telcagepant. In each treatment period, patients received 2 doses of telcagepant 300 mg or placebo 2 hours apart. They remained in the research center for 24 hours after receiving the first dose of each period, during which time continuous 12-lead ambulatory electrocardiographic (Holter) monitoring was performed.

Results.— Twenty-eight patients were enrolled; all patients completed the study and were included in all analyses. Telcagepant was generally well tolerated. No laboratory or serious adverse experiences were reported, and no patient discontinued due to an adverse experience. There were no consistent treatment-related changes in laboratory, vital signs or electrocardiogram safety parameters. Three patients (2 after receiving placebo and 1 after receiving telcagepant) experienced ST segment depression during the study; none of these patients reported chest pain.

Conclusions.— Two doses of 300-mg telcagepant, administered 2 hours apart, did not appear to exacerbate spontaneous ischemia and were generally well tolerated in a small cohort of patients with stable coronary artery disease. Results of this study support further evaluation of telcagepant in patients with stable coronary artery disease.

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