Inspire Pharmaceuticals, Inc. - INS37217 Respiratory Clinical Trials

Phase 1 Trials
Two Phase 1 trials in healthy volunteers and one Phase 1/2 trial in CF patients have demonstrated that denufosol is well tolerated in children and adults at multiple doses.

Phase 2 Trials
Trial 08-103
This trial was a double-blind, randomized comparison of three doses of denufosol (20 mg, 40 mg and 60 mg) to placebo administered three times daily for 28 days by jet nebulizer in 90 CF patients with early lung disease (FEV1 > 75%). Results from this trial were reported in April 2004 and demonstrated that denufosol was well tolerated at the three doses tested in the trial. In addition, at the end of the 28-day trial, patients receiving drug had significantly better lung function than patients receiving placebo, as determined by multiple spirometry measures. The majority of the external costs for this trial were funded by Cystic Fibrosis Foundation Therapeutics (CFFT).

CYSTIC FIBROSIS FOUNDATION - The Cystic Fibrosis Foundation (CFF) was established in 1955 to assure the development of the means to cure and control cystic fibrosis and to improve the quality of life for those with the disease. The CFF supports the full spectrum of drug development, including research, pre-clinical and clinical infrastructure. This includes support and accreditation of CF care centers, grants and research funds for promising therapies, funding of a network of CF research centers and support of clinical trials through the Therapeutic Development Network and Coordinating Center. More information on the CFF can be obtained through their website at www.cff.org.

ORPHAN DRUG STATUS - A category granted by the FDA for drugs to treat very rare diseases. The designation provides tax and patent incentives to drug companies that develop and market the treatment.

FAST TRACK DESIGNATION - The FDA considers Fast Track designation for products that have the potential to address unmet medical needs for serious or life-threatening conditions. Programs that have Fast Track designation may be considered for priority review or for accelerated approval based on surrogate endpoints. In addition, companies may be allowed to submit portions of an NDA early or to have early consultation with the FDA.

Trial 08-104
This trial was a double-blind, randomized comparison of two doses of denufosol (20 mg and 60 mg) to placebo administered three times daily for 28 days by jet nebulizer in 72 CF patients. Results from this trial were reported in October 2005. Trial 08-104 was not designed or powered to demonstrate statistically significant differences between denufosol and placebo with respect to efficacy, and no statistically significant differences were observed. The 20 mg dose was generally well tolerated across all patients enrolled in Trial 08-104. As observed in previous trials, both the 20 mg and 60 mg doses of denufosol were generally well tolerated in the patient population with milder disease (FEV1 of 75-90%). Patients with lower lung function (FEV1 of 60-74%) reported more respiratory adverse events across all treatment groups compared to patients with milder disease. Some of these events were acute transient declines in lung function following initial dosing that led to trial withdrawals, in particular in the 60 mg group.

Trial 08-107
Trial 08-107 was a double-blind, randomized, placebo-controlled, parallel group trial compared two doses of denufosol tetrasodium inhalation solution to placebo over 28 days of dosing in 13 CF patients, five to seven years of age. Results demonstrated that both the 20 mg and 60 mg doses of denufosol administered three times daily were well tolerated, with a safety profile similar to placebo. The most common adverse event in the trial was cough, which occurred in 50% of patients on denufosol and 40% of patients on placebo. There were no serious adverse events or patient withdrawals during the trial. In addition, results demonstrated that children in this age group were able to reliably perform the lung function tests to measure FEV1. The trial provides evidence for the feasibility of studying 5-7 year old CF patients and supports the inclusion of this patient population in Phase 3 trials.