A Placebo and Active Controlled Study of ONO-6950 Following Allergen Challenge in Patients With Asthma

A Double-blind, Placebo-controlled, Three-way Crossover Study to Compare the Safety and Efficacy of 8 Days of Therapy With ONO-6950 Versus Placebo and Montelukast (Singulair®) on Asthmatic Responses and Airway Hypersensitivity Following Allergen Challenge in Patients With Asthma

The primary objectives are

• to determine the effect of ONO-6950 200 mg QD versus placebo administered for 8 days on early asthmatic response (EAR) and late asthmatic response (LAR) induced by inhaled allergen
• to determine the safety and tolerability of ONO-6950 200 mg QD administered for 8 days in patients with asthma

The secondary objectives are:

• to compare the effect of ONO-6950 versus montelukast on the % decrease of FEV1 following allergen exposure, and
• to determine the effect of ONO-6950 versus placebo and montelukast on allergen-induced airway hyperresponsiveness (AHR) as measured by methacholine challenge

The study will examine if ONO-6950 could alleviate EAR and LAR caused by an allergen challenge in subjects with asthma. Patients will be required to have EAR and LAR after standardized allergen challenges during the screening. Eligible patients will complete a randomized, double-blind, three-way crossover study. During each of three evaluation periods, patients will be administered either 200 mg ONO-6950, 10 mg Montelukast, or placebo for 8 days. Each evaluation period will occur over 8 days and will include various assessments following allergen challenge and methacholine challenge. The study does not require an overnight stay at the clinical research center.

Inclusion Criteria:

• Patients of both genders, between 18 to 60 years of age, with bronchial asthma symptoms for at least 6 months
• Patients with FEV1 ≥ 70% of predicted after withholding short-acting β agonists for at least 8 hours prior to testing
• Screening allergen challenge demonstrates that the patient experiences both an early and late asthmatic response
• Sensitivity to methacholine resulting in a ≥ 20% fall in FEV1 (PC20 methacholine)
• 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
• 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
• Significant safety laboratory, ECG, or vital sign abnormalities that would place the patient at undue disk during the study procedures
• History of clinically significant multiple drug or food allergy