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.

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • Los Angeles Clinical Site 110
    • San Diego, California, United States, 92123
      • San Diego Clinical Site 140
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Clinical Site 160
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • North Dartmouth Clincial Site 150
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Minneapolis Clinical Site 190
  • New Jersey
    • Princeton, New Jersey, United States, 08558
      • Princeton Clinical Site 170
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Clinical Site 130
  • Texas
    • New Braunfels, Texas, United States, 78130
      • New Braunfeis Clinical Site 120
    • San Antonio, Texas, United States, 78229
      • San Antonio Clinical Site 180

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 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): November 1, 2012

Study Registration Dates

• First Submitted: February 15, 2012
• First Submitted That Met QC Criteria: February 17, 2012
• First Posted (ESTIMATE): February 20, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2014
• Last Update Submitted That Met QC Criteria: January 21, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: asthma; Adult
• 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-6950POU006