A Placebo and Active Controlled Study of ONO-6950 in Asthmatic Patients

A Double-blind, Placebo-controlled, Four-way Crossover Study to Compare the Safety and Efficacy of ONO-6950 20 mg and 200 mg QD Versus Placebo and Montelukast (Singulair) in Asthmatic Patients Who Experience Exercise-induced Bronchoconstriction

The primary objectives of this study are:

i. to determine the effect of single oral doses (20 and 200 mg) of ONO-6950 versus placebo on exercise induced bronchoconstriction (EIB) as percent attenuation in the decrease of forced expiratory volume in 1 second (FEV1) after exercise challenge

ii. to determine the safety and tolerability of single dose administrations of 20 and 200 mg of ONO-6950 in asthmatic patients.

The secondary objectives of this study are:

i. to compare the effect of different (20 and 200 mg) single oral doses of ONO-6950 versus montelukast (10 mg) on EIB as percent attenuation in the decrease of FEV1 after exercise challenge

ii. to determine the ratio of responders/non-responders in FEV1 for different (20 and 200 mg) single oral doses of ONO-6950 in comparison to montelukast (10 mg) and placebo.

The study will examine if ONO-6950 could alleviate EIB in asthmatic patients. Eligible patients will complete a randomized, double-blind, four-way crossover study. During each of four evaluation periods, patients will be administered a single dose of either 20 or 200 mg ONO-6950, 10 mg Montelukast, or placebo. Each evaluation period include various assessments following exercise challenge in an ambulatory setting.

Inclusion Criteria:

• Patients of both genders, between 18 to 60 years of age, with bronchial asthma for at least 6 months and history of exercise induced bronchospasm
• Patients with FEV1 ≥ 70% of predicted after withholding short-acting β agonists for at least 8 hours prior to testing
• Screening exercise challenge demonstrates that the patient experiences a fall in FEV1 of ≥ 20%
• Non-smokers with free from the usage of nicotine-containing products at least for a year prior to screening

Exclusion Criteria:

• Previous history of life-threatening asthma, respiratory tract infection and/or exacerbation of asthma within 6 weeks prior to the first screening visit
• History of being unable to tolerate or complete an exercise challenge and clinically significant multiple drug or food allergies
• Past or present disorders and diseases including, but are not limited to cardiovascular, malignancy, hepatic, renal, hematological, neurological, psychiatric, endocrine, or pulmonary other than asthma
• Patients with Seasonal Allergic Rhinitis (SAR) or seasonal allergic asthma,with significant symptoms that may confound study assessment
• Significant safety laboratory, ECG, or vital sign abnormalities that would place the patient at undue risk during the study procedures