By Frances Bishopp

Staff Writer

Interneuron Pharmaceuticals Inc. reported a preliminary analysis of its second Phase III clinical trial for oral citicoline (500 milligrams) in the treatment of ischemic stroke showed significantly improved neurological function among patients with moderate to severe stroke, but showed no significant benefit over placebo for patients with mild stroke.

William Boni, vice president of corporate communications at Interneuron, said the company will file for a new drug application (NDA) before the end of 1997, but, as yet, the company had not decided whether the application would be for all stroke or just for moderate to severe stroke.

Interneuron's stock (NASDAQ:IPIC) closed Wednesday at $19.25, up $1.25.

In the study, 267 patients received citicoline and 127 patients received placebo. The primary outcome analysis of the double-blind, placebo-controlled trials was improvement in the Barthel Index (a standard of measuring neurologic function that uses a 100-point rating scale) three months after an ischemic stroke.

Patients with moderate to severe stroke treated with citicoline had a 64 percent greater chance of complete or near-complete recovery relative to patients with moderate to severe stroke treated with placebo.

The study was influenced by a preponderance of mild cases in the placebo group, and as a result of the imbalance and other statistical factors, Interneuron said the primary analysis of the study, which encompassed all patients, was statistically invalid and could not be performed.

Interneuron, of Lexington, Mass., said because of the patient imbalance and other unmet requirements in the study, the analysis was rendered statistically invalid. "We learned from the study that people with mild stroke tend to improve no matter if they are treated or are left untreated," Boni said.

"Because of the randomization, there was a very high number of patients who had mild stroke in both placebo and drug, but a statistically significant higher number in the drug group. It skewed the analysis," Boni said.

Citicoline, a small molecule, is believed to limit the extent of the infarct, or tissue damage, caused by interrupted blood flow by preventing the accumulation of toxic-free fatty acids. It also promotes recovery of brain function by providing two components, cytidine and choline, required in the formation of nerve cell membranes.

Citicoline has a 24-hour window of therapeutic opportunity after a stroke occurs, Boni said, which is considerably wider than other drugs under development. Also, citicoline's safety profile has been well established with no serious adverse events reported. *