No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor ofneurogenic inflammation: Results of two randomized, double-blind, placebo controlled clinical trials

CP-122,288 is a highly potent inhibitor of neurogenic plasma extravasation in animal models at doses without vasoconstrictor effect. We evaluated the acute antimigraine efficacy of intravenous and oral CP-122,288 in two doubl e blind studies. In a crossover design, patients randomly received 31.25 mu g of CP-122,288 intravenously, placebo, or both. In the oral study, patien ts received placebo or one of four doses of CP-122,288 between 3.125 and 31 2.5 mu g, using a novel "up and down" design for randomization. Both studie s were stopped prematurely when target efficacy could not be achieved. Resp onder rates were 29% for CP-122,288 versus 30% for placebo (difference, -1% ; 95% CI, -24-22%; intravenous study) and an overall rate of 25% for CP-122 ,288 versus 0% for placebo(difference, 25%; 95% CI; 10-40%; oral study). CP -122,288 was not clinically effective at doses and plasma concentrations in excess of those required to inhibit neurogenic plasma extravasation in ani mals. Neurogenic plasma extravasation is unlikely to play a crucial role in the pathophysiology of migraine headache.