title: No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor of neurogenic inflammation: results of two randomized, double-blind, placebo-controlled clinical trials.
abstract: 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 double-blind studies. In a crossover design, patients randomly received 31.25 microg of CP-122,288 intravenously, placebo, or both. In the oral study, patients received placebo or one of four doses of CP-122,288 between 3.125 and 312.5 microg, using a novel "up and down" design for randomization. Both studies were stopped prematurely when target efficacy could not be achieved. Responder 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 animals. Neurogenic plasma extravasation is unlikely to play a crucial role in the pathophysiology of migraine headache.
authors.affiliation: Department of Neurology, Leiden University Medical Centre, The Netherlands.
authors.forename: K I
authors.initials: KI
authors.lastname: Roon
authors.forename: J
authors.initials: J
authors.lastname: Olesen
authors.forename: H C
authors.initials: HC
authors.lastname: Diener
authors.forename: P
authors.initials: P
authors.lastname: Ellis
authors.forename: J
authors.initials: J
authors.lastname: Hettiarachchi
authors.forename: P H
authors.initials: PH
authors.lastname: Poole
authors.forename: I
authors.initials: I
authors.lastname: Christianssen
authors.forename: D
authors.initials: D
authors.lastname: Kleinermans
authors.forename: J G
authors.initials: JG
authors.lastname: Kok
authors.forename: M D
authors.initials: MD
authors.lastname: Ferrari
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D020078:Neurogenic Inflammation / Q000517:prevention & control*; D010919:Placebos; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000627:therapeutic use; D018170:Sumatriptan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017211:Treatment Failure
chemical_list: D010919:Placebos; D011759:Pyrrolidines; D017366:Serotonin Receptor Agonists; C085263:CP 122288; D018170:Sumatriptan