Neurology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Published online before print October 3, 2007, doi:10.1212/01.WNL.0000286940.29755.61)
This Article
Right arrow Full Text (Rapid PDF)
Right arrow CME: Take the course for this article:
 Volume 70, Number 16, April 15, 2008
Right arrow Podcast
Right arrow All Versions of this Article:
01.WNL.0000286940.29755.61v1
70/16/1304    most recent
Right arrow Correspondence:
Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when Correspondence are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ho, T. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ho, T. W.
Received March 30, 2007
Accepted June 25, 2007

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

T. W. Ho MD*, L. K. Mannix MD, X. Fan PhD, C. Assaid PhD, C. Furtek BS, C. J. Jones MS, C. R. Lines PhD, A. M. Rapoport MD, On behalf of the MK-0974 Protocol 004 study group

From Merck Research Laboratories (T.W.H., X.F., C.A., C.F., C.J.J., C.R.L.), North Wales, PA; Headache Associates/ClinExcel Research (L.K.M.), Cincinnati, OH; and The New England Center for Headache (A.M.R.), Stamford, CT.


* To whom correspondence should be addressed. E-mail: tony_ho{at}merck.com.

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. A generally similar efficacy pattern was seen on other endpoints. MK-0974 appeared to be 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 receptor antagonist, MK-0974, was effective and generally well tolerated for the acute treatment of migraine.




This article has been cited by other articles:


Home page
 BrainHome page
M.-L. Sixt, K. Messlinger, and M. J. M. Fischer
Calcitonin gene-related peptide receptor antagonist olcegepant acts in the spinal trigeminal nucleus
Brain, November 1, 2009; 132(11): 3134 - 3141.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
K. M. Connor, R. E. Shapiro, H. -C. Diener, S. Lucas, J. Kost, X. Fan, K. Fei, C. Assaid, C. Lines, and T. W. Ho
Randomized, controlled trial of telcagepant for the acute treatment of migraine
Neurology, September 22, 2009; 73(12): 970 - 977.
[Abstract] [Full Text] [PDF]

Home page
 JDRHome page
R. Ambalavanar and D. Dessem
Emerging Peripheral Receptor Targets for Deep-tissue Craniofacial Pain Therapies
Journal of Dental Research, March 1, 2009; 88(3): 201 - 211.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
B. J. Van der Schueren, M. W. Lunnon, B. E. Laurijssens, F. Guillard, J. Palmer, A. Van Hecken, M. Depre, F. H. Vanmolkot, and J. N. de Hoon
Does the Unfavorable Pharmacokinetic and Pharmacodynamic Profile of the iNOS Inhibitor GW273629 Lead to Inefficacy in Acute Migraine?
J. Clin. Pharmacol., March 1, 2009; 49(3): 281 - 290.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. P. Regan, G. L. Stump, S. A. Kane, and J. J. Lynch Jr.
Calcitonin Gene-Related Peptide Receptor Antagonism Does Not Affect the Severity of Myocardial Ischemia during Atrial Pacing in Dogs with Coronary Artery Stenosis
J. Pharmacol. Exp. Ther., February 1, 2009; 328(2): 571 - 578.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
R. Guo, X.-P. Chen, X. Guo, L. Chen, D. Li, J. Peng, and Y.-J. Li
Evidence for Involvement of Calcitonin Gene-Related Peptide in Nitroglycerin Response and Association With Mitochondrial Aldehyde Dehydrogenase-2 (ALDH2) Glu504Lys Polymorphism
J. Am. Coll. Cardiol., September 9, 2008; 52(11): 953 - 960.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
J. M. Hansen, L. L. Thomsen, J. Olesen, and M. Ashina
Calcitonin gene-related peptide does not cause the familial hemiplegic migraine phenotype
Neurology, September 9, 2008; 71(11): 841 - 847.
[Abstract] [Full Text] [PDF]

Home page
 NeurologyHome page
P. J. Goadsby
Calcitonin gene-related peptide (CGRP) antagonists and migraine: Is this a new era?
Neurology, April 15, 2008; 70(16): 1300 - 1301.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2007 by AAN Enterprises, Inc.