PathoGenesis Corp has begun to enroll patients in an open-label, randomized Phase IV clinical trial of TOBI (tobramycin solution for inhalation) in cystic fibrosis patients with mild lung disease.

PathoGenesis plans to enroll up to 400 people, ages 6-15, who have cystic fibrosis (CF) and Pseudomonas aeruginosa lung infections but who have not yet experienced a major decline in lung function. At the beginning of the trial, patients' pulmonary function will be 70 percent to 90 percent of normal levels, as defined by forced expiratory volume at one second (FEV1).

The 14-month study will compare patients receiving TOBI and routine care to patients receiving routine care only. Up to 45 U.S. cystic fibrosis centers are expected to participate.

The trial's primary objective is to study the effect of TOBI on patients' rate of lung function decline, as well as to study the overall rate of lung function decline experienced by younger cystic fibrosis patients with mild lung disease. Most CF patients lose lung function over time, according to previous studies, and an estimated 85 percent eventually die because of the resulting respiratory failure.

The PathoGenesis study also will assess TOBI's effect on usage of other antibiotics, hospitalization frequency and duration, school days missed due to illness, and body weight.

"We're conducting this trial for both scientific and business reasons," said A. Bruce Montgomery, executive vice president of research and development. "In our pivotal trials, TOBI demonstrated dramatic benefits to CF patients with less than 75 percent of their normal lung function at baseline. The obvious question is, why wait until the lungs are 25 percent destroyed before starting chronic TOBI therapy? In fact, some doctors are starting TOBI therapy earlier. We're doing our mild CF trial to obtain scientific data on the effects of earlier TOBI therapy.

"From a business perspective, CF patients with mild lung disease represent a significant market opportunity for TOBI. Many of these patients are not taking TOBI -- or taking TOBI only to treat episodes of pulmonary symptom flare-ups. Our trial has been designed to provide data on early, chronic TOBI therapy."

TOBI is a patented, inhaled antibiotic. It is administered twice daily in repeated cycles of 28 days on drug, 28 days off drug, using a Pari LC Plus jet nebulizer and Pulmo-Aide compressor. Earlier pivotal clinical trials of TOBI were conducted in cystic fibrosis patients with more extensive lung disease.

This year, PathoGenesis plans to conduct or co-sponsor clinical trials of TOBI in cystic fibrosis and other patients, including bronchiectasis, ventilator-associated pneumonia and lung transplant patients.