Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine

T. W. Ho, L. K. Mannix, X. Fan, C. Assaid, C. Furtek, C. J. Jones, C. R. Lines, A. M. Rapoport

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To determine an effective and tolerable dose of a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, for the acute treatment of migraine. METHODS: Randomized, double-blind, parallel-group, clinical trial with a two-stage, adaptive, dose-ranging design. Patients were allocated to treat a moderate or severe migraine attack with MK-0974 (25, 50, 100, 200, 300, 400, or 600 mg), rizatriptan 10 mg, or placebo taken orally. The primary endpoint was pain relief (reduction to mild or none) 2 hours after dosing. Secondary endpoints included pain freedom at 2 hours and sustained pain relief at 24 hours. A prespecified, blinded, automated interim analysis was used to discontinue randomization to less effective doses. RESULTS: Per the adaptive study design, the four lowest MK-0974 groups (25, 50, 100, 200 mg) were discontinued due to insufficient efficacy. For the remaining treatment groups, the estimated pain relief proportions at 2 hours were 300 mg (n = 38) 68.1%, 400 mg (n = 45) 48.2%, 600 mg (n = 40) 67.5%, rizatriptan 10 mg (n = 34) 69.5%, and placebo (n = 115) 46.3%. The prespecified primary efficacy hypothesis test, which compared the average 2-hour pain relief response proportion of the combined 300, 400, and 600 mg MK-0974 groups to placebo, was significant (P = 0.015). A generally similar efficacy pattern was seen for other endpoints. MK-0974 was generally well tolerated and there did not appear to be an increase in adverse events with increasing dose. CONCLUSIONS: The novel, orally administered calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, was effective and generally well tolerated for the acute treatment of migraine.

Original languageEnglish (US)
Pages (from-to)1304-1312
Number of pages9
JournalNeurology
Volume70
Issue number16
DOIs
StatePublished - Apr 2008
Externally publishedYes

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Calcitonin Gene-Related Peptide Receptors
Migraine Disorders
Randomized Controlled Trials
Pain
Placebos
Therapeutics
Random Allocation
telcagepant
Clinical Trials

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ho, T. W., Mannix, L. K., Fan, X., Assaid, C., Furtek, C., Jones, C. J., ... Rapoport, A. M. (2008). Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. Neurology, 70(16), 1304-1312. https://doi.org/10.1212/01.WNL.0000286940.29755.61

Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. / Ho, T. W.; Mannix, L. K.; Fan, X.; Assaid, C.; Furtek, C.; Jones, C. J.; Lines, C. R.; Rapoport, A. M.

In: Neurology, Vol. 70, No. 16, 04.2008, p. 1304-1312.

Research output: Contribution to journalArticle

Ho, TW, Mannix, LK, Fan, X, Assaid, C, Furtek, C, Jones, CJ, Lines, CR & Rapoport, AM 2008, 'Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine', Neurology, vol. 70, no. 16, pp. 1304-1312. https://doi.org/10.1212/01.WNL.0000286940.29755.61
Ho, T. W. ; Mannix, L. K. ; Fan, X. ; Assaid, C. ; Furtek, C. ; Jones, C. J. ; Lines, C. R. ; Rapoport, A. M. / Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine. In: Neurology. 2008 ; Vol. 70, No. 16. pp. 1304-1312.
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T1 - Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in acute treatment of migraine

AU - Ho, T. W.

AU - Mannix, L. K.

AU - Fan, X.

AU - Assaid, C.

AU - Furtek, C.

AU - Jones, C. J.

AU - Lines, C. R.

AU - Rapoport, A. M.

PY - 2008/4

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N2 - OBJECTIVE: To determine an effective and tolerable dose of a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, for the acute treatment of migraine. METHODS: Randomized, double-blind, parallel-group, clinical trial with a two-stage, adaptive, dose-ranging design. Patients were allocated to treat a moderate or severe migraine attack with MK-0974 (25, 50, 100, 200, 300, 400, or 600 mg), rizatriptan 10 mg, or placebo taken orally. The primary endpoint was pain relief (reduction to mild or none) 2 hours after dosing. Secondary endpoints included pain freedom at 2 hours and sustained pain relief at 24 hours. A prespecified, blinded, automated interim analysis was used to discontinue randomization to less effective doses. RESULTS: Per the adaptive study design, the four lowest MK-0974 groups (25, 50, 100, 200 mg) were discontinued due to insufficient efficacy. For the remaining treatment groups, the estimated pain relief proportions at 2 hours were 300 mg (n = 38) 68.1%, 400 mg (n = 45) 48.2%, 600 mg (n = 40) 67.5%, rizatriptan 10 mg (n = 34) 69.5%, and placebo (n = 115) 46.3%. The prespecified primary efficacy hypothesis test, which compared the average 2-hour pain relief response proportion of the combined 300, 400, and 600 mg MK-0974 groups to placebo, was significant (P = 0.015). A generally similar efficacy pattern was seen for other endpoints. MK-0974 was generally well tolerated and there did not appear to be an increase in adverse events with increasing dose. CONCLUSIONS: The novel, orally administered calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, was effective and generally well tolerated for the acute treatment of migraine.

AB - OBJECTIVE: To determine an effective and tolerable dose of a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, for the acute treatment of migraine. METHODS: Randomized, double-blind, parallel-group, clinical trial with a two-stage, adaptive, dose-ranging design. Patients were allocated to treat a moderate or severe migraine attack with MK-0974 (25, 50, 100, 200, 300, 400, or 600 mg), rizatriptan 10 mg, or placebo taken orally. The primary endpoint was pain relief (reduction to mild or none) 2 hours after dosing. Secondary endpoints included pain freedom at 2 hours and sustained pain relief at 24 hours. A prespecified, blinded, automated interim analysis was used to discontinue randomization to less effective doses. RESULTS: Per the adaptive study design, the four lowest MK-0974 groups (25, 50, 100, 200 mg) were discontinued due to insufficient efficacy. For the remaining treatment groups, the estimated pain relief proportions at 2 hours were 300 mg (n = 38) 68.1%, 400 mg (n = 45) 48.2%, 600 mg (n = 40) 67.5%, rizatriptan 10 mg (n = 34) 69.5%, and placebo (n = 115) 46.3%. The prespecified primary efficacy hypothesis test, which compared the average 2-hour pain relief response proportion of the combined 300, 400, and 600 mg MK-0974 groups to placebo, was significant (P = 0.015). A generally similar efficacy pattern was seen for other endpoints. MK-0974 was generally well tolerated and there did not appear to be an increase in adverse events with increasing dose. CONCLUSIONS: The novel, orally administered calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, was effective and generally well tolerated for the acute treatment of migraine.

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