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

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: ONO-6950; Drug: Montelukast; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta, Canada, T2N4N1
    • Calgary Clinical Site 540
  • Ontario, Canada, L8N3Z5
    • Hamilton Clinical Site 550
  • Quebec City, Canada, G1V4GS
    • Quebec Clinical Site 510
  • Saskatoon, Canada, S7N0W8
    • Saskatoon Clinical Site 520
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T2B5
      • Vancouver Clinical Site 530

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Comparator	Drug: Placebo; Placebo to match ONO-6950 tablets or over-encapsulated Montelukast tablets dosed in a similar manner
Active Comparator: Active Comparator	Drug: Montelukast; 10 mg Montelukast QD for 8 days
Experimental: Experimental 200 mg dose	Drug: ONO-6950; 200 mg QD for 8 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Late Asthmatic Response (3-7 hours after allergen challenge) as measured by the AUC in FEV1	Day 7
Early Asthmatic Response as measured by the AUC in FEV1	Day 7
Late Asthmatic Response as measured by the Maximum Fall in FEV1	Day 7
Early Asthmatic Response as measured by the Maximum Fall in FEV1	Day 7

Secondary Outcome Measures

Outcome Measure	Time Frame
Differences in PC20 pre-post treatment as measured by methacholine challenge	Day 6
Differences in PC20 pre-post allergen challenge as measured by methacholine challenge	Day 8

Collaborators and Investigators

• Sponsor: Ono Pharma USA Inc
• Collaborators: Ono Pharmaceutical Co. Ltd

Publications and helpful links

General Publications

• Gauvreau GM, Boulet LP, FitzGerald JM, Cockcroft DW, Davis BE, Leigh R, Tanaka M, Fourre JA, Tanaka M, Nabata T, O'Byrne PM. A dual CysLT1/2 antagonist attenuates allergen-induced airway responses in subjects with mild allergic asthma. Allergy. 2016 Dec;71(12):1721-1727. doi: 10.1111/all.12987. Epub 2016 Aug 9.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: March 8, 2012
• First Submitted That Met QC Criteria: March 9, 2012
• First Posted (Estimate): March 12, 2012

Study Record Updates

• Last Update Posted (Estimate): April 30, 2013
• Last Update Submitted That Met QC Criteria: April 29, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: asthma; ONO-6950; asthma in adult patients
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: ONO-6950POU005