Authors: Jes Olesen, M.D., Hans-Christoph Diener, M.D., Ingo W. Husstedt, M.D., Peter J. Goadsby, M.D., David Hall, Ph.D., Ulrich Meier, Ph.D., Stephane Pollentier, M.D., and Lynna M. Lesko, M.D., for the BIBN 4096 BS Clinical Proof of Concept Study Group
Source: N Engl J Med 2004; 350:1104-1110 March 11, 2004
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.
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.
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.
The CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine.