title: Effect of telcagepant on spontaneous ischemia in cardiovascular patients in a randomized study.
abstract: 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.
authors.affiliation: From Merck & Co., Inc., North Wales, PA, USA. martin_behm@merck.com
authors.forename: Martin O
authors.initials: MO
authors.lastname: Behm
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Blanchard
authors.forename: M Gail
authors.initials: MG
authors.lastname: Murphy
authors.forename: John S
authors.initials: JS
authors.lastname: Palcza
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Harris
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Butterfield
authors.forename: William B
authors.initials: WB
authors.lastname: Smith
authors.forename: Richard A
authors.initials: RA
authors.lastname: Preston
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Chodakewitz
authors.forename: Mitchell W
authors.initials: MW
authors.lastname: Krucoff
mesh_terms: D000328:Adult; D000368:Aged; D001381:Azepines / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000150:complications / Q000188:drug therapy; D017202:Myocardial Ischemia / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control*
chemical_list: D001381:Azepines; D007093:Imidazoles; C525458:telcagepant