Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine: A multicentre, randomised, double-blind, placebo-controlled, phase 2b study

Marcelo E. Bigal, David W. Dodick, Alan M. Rapoport, Stephen D. Silberstein, Yuju Ma, Ronghua Yang, Pippa S. Loupe, Rami Burstein, Lawrence C. Newman, Richard B. Lipton

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Abstract

Background: Calcitonin gene-related peptide (CGRP) is a validated target for the treatment of episodic migraine. Here we assess the safety, tolerability, and efficacy of TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of high-frequency episodic migraine. Methods: In this multicentre, randomised, double-blind, placebo-controlled, phase 2b study, we enrolled men and women (aged 18-65 years) from 62 sites in the USA who had migraine headaches 8-14 days per month. Using a randomisation list generated by a central computerised system and an interactive web response system, we randomly assigned patients (1:1:1; stratified by sex and use of concomitant preventive drugs) after a 28 day run-in period to three 28 day treatment cycles of subcutaneous 225 mg TEV-48125, 675 mg TEV-48125, or placebo. Investigators, patients, and the funder were blinded to treatment allocation. Patients reported headache information daily using an electronic diary. Primary endpoints were change from baseline in migraine days during the third treatment cycle (weeks 9-12) and safety and tolerability. The secondary endpoint was change relative to baseline in headache-days during weeks 9-12. Efficacy endpoints were analysed for the intention-to-treat population. Safety and tolerability were analysed using descriptive statistics. This trial is registered at ClinicalTrials.gov, number NCT02025556. Findings: Between Jan 8, 2014, and Oct 15, 2014, we enrolled 297 participants: 104 were randomly assigned to receive placebo, 95 to receive 225 mg TEV-48125, and 96 to receive 675 mg TEV-48125. The least square mean (LSM) change in number of migraine-days from baseline to weeks 9-12 was -3.46 days (SD 5.40) in the placebo group, -6.27 days (5.38) in the 225 mg dose group, and -6.09 days (5.22) in the 675 mg dose group. The LSM difference in the reduction of migraine-days between the placebo and 225 mg dose groups was -2.81 days (95% CI -4.07 to -1.55; p

Original languageEnglish (US)
Pages (from-to)1081-1090
Number of pages10
JournalThe Lancet Neurology
Volume14
Issue number11
DOIs
StatePublished - Nov 1 2015

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Migraine Disorders
Placebos
Safety
Calcitonin Gene-Related Peptide
Least-Squares Analysis
Headache
Therapeutics
Random Allocation
TEV-48125
Research Personnel
Antibodies
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Clinical Neurology

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Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine : A multicentre, randomised, double-blind, placebo-controlled, phase 2b study. / Bigal, Marcelo E.; Dodick, David W.; Rapoport, Alan M.; Silberstein, Stephen D.; Ma, Yuju; Yang, Ronghua; Loupe, Pippa S.; Burstein, Rami; Newman, Lawrence C.; Lipton, Richard B.

In: The Lancet Neurology, Vol. 14, No. 11, 01.11.2015, p. 1081-1090.

Research output: Contribution to journalArticle

Bigal, Marcelo E. ; Dodick, David W. ; Rapoport, Alan M. ; Silberstein, Stephen D. ; Ma, Yuju ; Yang, Ronghua ; Loupe, Pippa S. ; Burstein, Rami ; Newman, Lawrence C. ; Lipton, Richard B. / Safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine : A multicentre, randomised, double-blind, placebo-controlled, phase 2b study. In: The Lancet Neurology. 2015 ; Vol. 14, No. 11. pp. 1081-1090.
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T2 - A multicentre, randomised, double-blind, placebo-controlled, phase 2b study

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AU - Dodick, David W.

AU - Rapoport, Alan M.

AU - Silberstein, Stephen D.

AU - Ma, Yuju

AU - Yang, Ronghua

AU - Loupe, Pippa S.

AU - Burstein, Rami

AU - Newman, Lawrence C.

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