GLASGOW, Scotland PP A small Scottish pharmaceuticalcompany has begun Phase II trials of its proprietarycontrolled-release vaginal insert to treat fungal infection.

Core Technologies Ltd. of East Kilbride, a suburb of Galsgow,will shortly announce preliminary clinical results obtained withthe drug-dispensing device in a small group of womensuffering from genital infection by Candida albicans.

The initial stage of the Phase II study is ongoing in fiveGlasgow region genito/urinary clinical centers. Next monthtesting will extend to a second cohort, including clinics atLondon's St. Thomas' Hospital and elsewhere in England.

"This first group of patients all experienced 100 percenteradication of their severe candidal infections within 48 hours,"Core's managing director, James Pickard, told BioWorld. He saidthe treatment dosage and duration study will enroll 100patients and end in August or September. "After that," Pickardadded, "we will move directly into Phase III," which will aim toprovide data for an approval application to Britain's MedicinesControl Agency (MCA). The trial will be extended to the U.S. assoon as Core obtains a marketing partner for North America.

The Phase III trials, Pickard explained, will measure efficacy"in direct comparison with competing topically appliedproducts." These are all instant-release rather than controlledformulations. In addition to genito/urinary clinics, he said, "wewill also try to hit general practitioners."

Candida albicans is one of the human body's most commonfungal residents. Inside the mouth and other external mucousmembranes (particularly in AIDS patients) it produces an itchy,patchy condition called thrush. In relatively rare visceralinfections it can cause severe, even life-threatening, disease.Women who are pregnant or on oral contraceptives areparticularly prone to the relatively harmless but acute tormentof recurrent vaginal candidiasis.

Core's controlled-release vaginal pessary, the company's firstproduct, consists of a hydrogel polymer cylinder the size andshape of a tampon, impregnated with miconazole nitrate, thestandard anti-Candida compound. Core holds exclusiveworldwide licenses to the patents protecting the hydrogelpolymer technology, which was invented and developed byNeil Graham at Glasgow's Strathclyde University.

The company licensed rights from British Technology Group(BTG), a privately held consortium of venture capitalistsdirected at commercializing academic discoveries.

Core's first-round funding in 1991 consisted of #150,000($225,000), which was put up as seed money by its founders.An additional $525,000 came in 1993 from a group led byPrelude Technology Investments Ltd. and supported byScottish Enterprise and BTG. Core hopes to raise $1.5 millionthis June from the same sources plus other investors. Pickardexpects that this new money will float the company through1995, with the sale of drug-delivery products yielding a profitin 1996.

The only rights Core does not have reside with another Kilbrideconcern, Controlled Therapeutics Ltd. of Scotland, whose parentcompany is PharmaSciences Inc. of West Conshohocken, Pa.That company last year sublicensed to Forest Laboratories ofNew York the franchise to produce a vaginal pessary forrelease of prostaglandin E2. This substance opens the cervix ofa pregnant woman at term and induces delivery.

The hydrogel, PharmaSciences' president and chief executive,Richard Storm, told BioWorld, is a highly cross-linkedpolyurethane polymer that is made using aliphatic isocyanates.

"The hydrogel polymer has undergone extensive toxicitytesting," Pickard said, "and as its active drug is already on themarket, it was approved by MCA for use via the vaginal route."(Thus, presumably, no Phase I trial was needed.)

After polymerizing and purifying the hydrogel, Core loads itwith the miconazole nitrate by solvent diffusion. Then, inclinical use, the vaginal environment of temperature andhumidity causes the anti-fungal drug to leach out over 12 to 24hours and attack the fungus.

Pickard, whose fledgling company has 12 employees, isnegotiating with about 10 companies to market the product,which Core will manufacture. A "substantial number" of theseprospective partners are American. "We wouldn't like to pre-empt their view of the price structure," he said. "It will becompetitively priced, targeted at the brand leader."

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.