Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention

Tony W. Ho, Kathryn M. Connor, Ying Zhang, Eric Pearlman, Janelle Koppenhaver, Xiaoyin Fan, Christopher Lines, Lars Edvinsson, Peter J. Goadsby, David Michelson

Research output: Contribution to journalArticle

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 ≥33the upper limit of normal and 7 of these also had an aspartate aminotransferase elevation ≥33 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. Classification of evidence: 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.

Original languageEnglish (US)
Pages (from-to)958-966
Number of pages9
JournalNeurology
Volume83
Issue number11
StatePublished - Sep 1 2014
Externally publishedYes

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Calcitonin Gene-Related Peptide Receptors
Migraine Disorders
Randomized Controlled Trials
Placebos
Transaminases
Alanine Transaminase
Headache
Clinical Trials Data Monitoring Committees
telcagepant
Placebo
Antagonist
Randomized Controlled Trial
Gene
Aspartate Aminotransferases
Elevation
Multicenter Studies
Therapeutics

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Ho, T. W., Connor, K. M., Zhang, Y., Pearlman, E., Koppenhaver, J., Fan, X., ... Michelson, D. (2014). Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. Neurology, 83(11), 958-966.

Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. / Ho, Tony W.; Connor, Kathryn M.; Zhang, Ying; Pearlman, Eric; Koppenhaver, Janelle; Fan, Xiaoyin; Lines, Christopher; Edvinsson, Lars; Goadsby, Peter J.; Michelson, David.

In: Neurology, Vol. 83, No. 11, 01.09.2014, p. 958-966.

Research output: Contribution to journalArticle

Ho, TW, Connor, KM, Zhang, Y, Pearlman, E, Koppenhaver, J, Fan, X, Lines, C, Edvinsson, L, Goadsby, PJ & Michelson, D 2014, 'Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention', Neurology, vol. 83, no. 11, pp. 958-966.
Ho TW, Connor KM, Zhang Y, Pearlman E, Koppenhaver J, Fan X et al. Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. Neurology. 2014 Sep 1;83(11):958-966.
Ho, Tony W. ; Connor, Kathryn M. ; Zhang, Ying ; Pearlman, Eric ; Koppenhaver, Janelle ; Fan, Xiaoyin ; Lines, Christopher ; Edvinsson, Lars ; Goadsby, Peter J. ; Michelson, David. / Randomized controlled trial of the CGRP receptor antagonist telcagepant for migraine prevention. In: Neurology. 2014 ; Vol. 83, No. 11. pp. 958-966.
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AU - Fan, Xiaoyin

AU - Lines, Christopher

AU - Edvinsson, Lars

AU - Goadsby, Peter J.

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N2 - 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 ≥33the upper limit of normal and 7 of these also had an aspartate aminotransferase elevation ≥33 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. Classification of evidence: 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.

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