By Chris Delporte

Interneuron Pharmaceuticals Inc. initiated a Phase III clinical trial with trospium in patients suffering from overactive bladder and urinary incontinence (UI).

The company acquired exclusive U.S. marketing rights to trospium from Germany-based Madaus AG in November 1999. Lexington, Mass.-based Interneuron is responsible for all U.S. clinical development and will make regulatory, royalty and sales milestone payments to Madaus. Terms of the deal were not disclosed.

This efficacy trial is the first in the U.S. and enrollment begins this month. The trial will include approximately 500 patients at 50 clinical sites. The double-blind study will compare the reduction in micturitions and incontinence episodes among trospium-treated patients and placebo-treated patients over 12 weeks. The company plans, assuming positive trial results, to file a new drug application with the FDA by the end of next year.

¿We have a very aggressive business development capability,¿ said William Boni, vice president of corporate communications for Interneuron. ¿That includes scouring Europe for compounds in clinical development with companies with similar corporate cultures to Interneuron. Madaus is one of those companies.¿

Trospium is part of a class of anticholinergic compounds called muscarinic receptor antagonists. These compounds relax smooth muscle tissue, such as bladder tissue. The company said that unlike current therapies for overactive bladder, preclinical data suggest that trospium does not cross the blood-brain barrier, which means it would cause fewer central nervous system side effects, including somnolence, headache, diminished concentration, reduced motor coordination, reduced reaction time and dizziness.

Interneuron also said because trospium is excreted primarily unchanged in urine and given the absence of active metabolites, there is the potential for reduced risk of drug interaction. Interneuron said this is especially important in the elderly population. The company recently completed an electrocardiogram safety trial with the drug that showed no clinically significant differences between patients treated with trospium and those given a placebo.

Trospium already is marketed throughout Europe by Madaus for overactive bladder and urinary incontinence. Clinical trials in Europe included a number of double-blind, placebo-controlled, randomized efficacy trials comparing trospium with tolterodine and oxybutynin, current standards of care marketing in both the U.S. and Europe.

Boni said that Interneuron¿s business model involves building its product pipeline though the acquisition and licensing of compounds with established clinical or late-stage preclinical data, in addition to seeking out alliances with companies with experience outside the U.S. Current corporate partners include Pfizer Inc., of New York, and Eli Lilly and Co., of Indianapolis.

¿We currently are looking at a number of options, including signing a licensing agreement with a larger pharma company,¿ Boni said, regarding the company¿s future development plans for trospium. ¿But I stress that that¿s only one of the options we¿re looking at right now.¿

The company said it expects the size of the U.S. drug market for UI to reach $1 billion by 2003 and $2 billion by 2008. In addition to its therapy for UI, Interneuron is focused on the development and commercialization of products for panic and anxiety disorders, liver disease, HIV and stroke.