title: Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention.
abstract: OBJECTIVE
  To evaluate whether the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant might be effective for migraine prevention.
  
  
  METHODS
  In this randomized, double-blind, placebo-controlled, multicenter trial (ClinicalTrials.gov NCT00797667), patients experiencing 3-14 migraine days during a 4-week baseline were randomized to telcagepant 140 mg, telcagepant 280 mg, or placebo twice daily for 12 weeks. Efficacy was assessed by mean monthly headache days and migraine/probable migraine days (headache plus ≥ 1 associated symptom).
  
  
  RESULTS
  The trial was terminated following a recommendation from the Safety Monitoring Board due to hepatotoxicity concerns. At termination, the planned 660 patients had been randomized, 656 had been treated with ≥ 1 dose of study medication, and 14 had completed the trial. The mean treatment duration was 48-50 days. Thirteen patients, all in the telcagepant groups, had an alanine aminotransferase (ALT) elevation ≥ 3 × the upper limit of normal and 7 of these also had an aspartate aminotransferase elevation ≥ 3 × the upper limit of normal. Two patients had very high symptomatic transaminase elevations that occurred within 2-6 weeks of treatment initiation and resolved after treatment discontinuation. The originally planned efficacy analysis over 12 weeks was not performed due to limited data at later time points, but there was evidence that telcagepant resulted in a larger reduction from baseline than placebo for mean monthly headache days (month 1: 140 mg = -2.9, 280 mg = -3.1, placebo = -1.7; p < 0.05) and migraine/probable migraine days (month 1: 140 mg = -2.7, 280 mg = -3.0, placebo = -1.6; p < 0.05).
  
  
  CONCLUSIONS
  These data suggest a potential role for CGRP receptor antagonism in migraine prophylaxis. However, the observed aminotransferase elevations do not support the use of telcagepant for daily administration.
  
  
  METHODS
  This study provides Class II evidence that in patients with migraine, telcagepant taken daily reduces headache days by 1.4 days per month compared to placebo and causes 2.5% of patients to have elevations of serum ALT levels.
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA.
authors.forename: Tony W
authors.initials: TW
authors.lastname: Ho
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Connor
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA.
authors.forename: Eric
authors.initials: E
authors.lastname: Pearlman
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA.
authors.forename: Janelle
authors.initials: J
authors.lastname: Koppenhaver
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Fan
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA.
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
authors.affiliation: From Merck & Co., Inc. (T.W.H., K.M.C., Y.Z., J.K., X.F., C.L., D.M.), Whitehouse Station, NJ; Mercer University School of Medicine (E.P.), Savannah, GA; Department of Medicine (L.E.), Institute of Clinical Sciences, Lund University and Lund University Hospital, Sweden; Headache Group (P.J.G.), NHIR-Wellcome Trust Clinical Research Facility, King's College London, UK; and Department of Neurology (P.J.G.), University of California, San Francisco. T.W.H. is currently affiliated with AstraZeneca Pharmaceuticals LP, Wilmington, DE. X.F. is currently affiliated with Elan Corporation, Boston, MA. david_michelson@merck.com.
authors.forename: David
authors.initials: D
authors.lastname: Michelson
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001381:Azepines / Q000009:adverse effects / Q000627:therapeutic use*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008881:Migraine Disorders / Q000097:blood / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D001381:Azepines; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007093:Imidazoles; C525458:telcagepant; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase