Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine.
BACKGROUND
Calcitonin gene-related peptide (CGRP) may have a causative role in migraine. We therefore hypothesized that a CGRP-receptor antagonist might be effective in the treatment of migraine attacks.


METHODS
In an international, multicenter, double-blind, randomized clinical trial of BIBN 4096 BS, a highly specific and potent nonpeptide CGRP-receptor antagonist, 126 patients with migraine received one of the following: placebo or 0.25, 0.5, 1, 2.5, 5, or 10 mg of BIBN 4096 BS intravenously over a period of 10 minutes. A group-sequential adaptive treatment-assignment design was used to minimize the number of patients exposed.


RESULTS
The 2.5-mg dose was selected, with a response rate of 66 percent, as compared with 27 percent for placebo (P=0.001). The BIBN 4096 BS group as a whole had a response rate of 60 percent. Significant superiority over placebo was also observed with respect to most secondary end points: the pain-free rate at 2 hours; the rate of sustained response over a period of 24 hours; the rate of recurrence of headache; improvement in nausea, photophobia, phonophobia, and functional capacity; and the time to meaningful relief. An effect was apparent after 30 minutes and increased over the next few hours. The overall rate of adverse events was 25 percent after the 2.5-mg dose of the drug and 20 percent for the BIBN 4096 BS group as a whole, as compared with 12 percent for placebo. The most frequent side effect was paresthesia. There were no serious adverse events.


CONCLUSIONS
The CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine.
Olesen
Jes
J
Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark. jeol@glostruphosp.kbhamt.dk
Diener
Hans-Christoph
HC
Husstedt
Ingo W
IW
Goadsby
Peter J
PJ
Hall
David
D
Meier
Ulrich
U
Pollentier
Stephane
S
Lesko
Lynna M
LM
D000208:Acute Disease; D000328:Adult; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D010879:Piperazines; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010879:Piperazines; D010880:Piperidines; D011799:Quinazolines; C406305:olcegepant