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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: ONO-6950
* Drug: ONO-6950
* Drug: Montelukast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental 200 mg dose<br> | Drug: ONO-6950<br>* 200 mg QD, single dose<br>|
| Experimental: Experimental 20 mg dose<br> | Drug: ONO-6950<br>* 20 mg QD, single dose<br>|
| Active Comparator: Active Comparator Montelukast<br> | Drug: Montelukast<br>* 10 mg Montelukast, QD single dose<br>|
| Placebo Comparator: Placebo Comparator<br> | Drug: Placebo<br>* Placebo to match ONO-6950 tablets or leukotriene receptor antagonist (LTRA) tablets dosed in a similar manner<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inhibition of maximum fall in Forced Expiratory Volume in One Second (FEV1) after exercise |  | 60 minutes following the exercise challenge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC (0-30 min) | area under the concentration time curve integrating fall in FEV1 following exercise over the 30 minute interval immediately following exercise | 30 minutes following the exercise challenge | 
| AUC (0-60 min) | area under the concentration time curve integrating fall in FEV1 following exercise over the 60 minute interval immediately following exercise | 60 minutes following the exercise challenge | 
| Time to recovery of FEV1 to within 5% of the pre-exercise baseline |  | 90 minutes following the exercise challenge | 
| Proportion of patients using a short acting beta agonist (rescue medication) |  | 90 minutes following the exercise challenge | 
| Ratio of responder/non-responder in FEV1 |  | 60 minutes following the exercise challenge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, Adult