Cambridge NeuroScience Inc. said Wednesday it began a Phase IIIpivotal trial of Cerestat in a 700-patient study for traumatic braininjury.
The double-blind, placebo-controlled trial is expected to includeabout 40 sites in North America and 30 in Europe. The trial is beingrun in collaboration with Cerestat partner Boehringer IngelheimGmbH, of Ingelheim, Germany.
The company said 70 sites will be used to help expedite enrollment.Nearly all of the centers have dedicated trauma facilities withspecialized critical care capabilities. Patients will be stratified basedon degree of injury then randomized to receive placebo or a fixeddose of Cerestat.
"Cerestat is now one of only a handful of drugs targeted to traumaticbrain injury [TBI] that are in advanced development, and is the onlyone employing this particular mechanism," said Elkan Gamzu,president and CEO of Cambridge, Mass.-based CambridgeNeuroScience.
The product is a N-Methyl-D-Aspartate (NMDA) ion channelblocker that prevents nerve cell death and brain damage followingstroke or head injury by preventing excessive entry of calcium intonerve cells.
Harry Wilcox, senior vice president and chief financial officer atCambridge NeuroScience, said the company hopes to accrue allpatients in about one year. Patients will be followed six months aftertreatment.
In October 1995 Cambridge NeuroScience released data from aPhase II study showing non-weight-adjusted doses of Cerestatproduced the desired plasma levels. The fixed dosing regimen, whichwill be used in the pivotal study, is an initial 15 mg bolus followed by3 mg of drug delivered intravenously every hour for 72 hours. (SeeBioWorld Today, Oct. 3, 1995, p. 5.)
Having a fixed dose makes Cerestat easier to use in emergencyclinical situations. It also offers marketing benefits.
Wilcox said an interim analysis incorporated into the trial will look atsafety aspects. Later this year, Wilcox said, Cambridge NeuroScienceand Ingelheim intend to start a pivotal trial of Cerestat in stroke thatwill encompass about 900 patients and 90 centers.
The primary endpoint in the TBI study is performance as measuredby the Glasgow Outcome Score, a five-point scale measuring clinicaloutcome following neurological injury. The scale ranges from deathto normal neurological abilities. Scores will be assigned at baselineand at six months.
"Our goal is to make a clinically significant difference for thesepatients," Wilcox said. "We want patients to be able to care forthemselves."
Secondary endpoints include disability and pharmacoeconomicmeasures.
Cambridge NeuroScience and Boehringer Ingelheim announced theirintention to collaborate on Cerestat development in January 1995 in adeal worth up to $43 million to Cambridge NeuroScience. Ingelheimpaid $15 million up front, and in 1995 contributed an additional $3million in development costs, Wilcox said.
Ingelheim is funding at least 75 percent of development costs in theU.S. and Europe, and all development in Japan. CambridgeNeuroScience has co-promotion rights in the U.S. and would getroyalties on sales elsewhere.
Cambridge NeuroScience's stock (NASDAQ:CNSI) gained as muchas $1 Wednesday before closing at $10.13, up 38 cents. n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.