This is a Phase II, double-blind, placebo-controlled, cross-over trial to evaluate the efficacy of AIM-102 for the treatment of allergen-induced asthma. Individuals with stable, mild to moderate allergic asthma by American Thoracic Society (ATS) criteria (1), with a history of episodic wheeze and shortness of breath, will be eligible for enrollment. The patients will receive 4 consecutive days of dosing of AIM-102 or placebo (inactive product) with an allergen challenge on day 3 of dosing to see how the patient's lung function is changed by using AIM-102 or placebo.
This is a Phase II, double-blind, placebo-controlled, cross-over trial to evaluate the efficacy of AIM-102 for the treatment of allergen-induced asthma. Individuals with stable, mild to moderate allergic asthma by American Thoracic Society (ATS) criteria (1), with a history of episodic wheeze and shortness of breath, will be eligible for enrollment. The study is divided into 2 parts. Part 1: Screening Patients who meet all entry criteria will be screened with a history, physical examination, spirometry, and routine laboratory tests. If they continue to meet entry criteria, their atopic status will be documented by skin testing against common airborne allergens (including cat, dust mite, grass, pollen). Twenty-four (24) hr later, an allergen challenge will be performed to confirm the presence of an Early Asthmatic Response (EAR) and Late Asthmatic Response (LAR). Methacholine PC20 and sputum differentials will be performed before and after allergen challenges. Only patients with a documented early and late asthmatic response to inhaled incremental allergen challenge will be eligible for entry into Part 2 of the study. Part 2: Dosing and Follow-up Patients will be assigned to receive drug and placebo in a random order, with at least a two week washout between treatment periods. Spirometry, vital signs, and asthma symptomatology, methacholine challenge, sputum differentials will be evaluated before the first dose and again 24 hr before allergen challenge. Allergen challenge will be performed in the morning of Day 3 of dosing, post-dose, with spirometry measured until seven hr post-challenge. Sputum will also be induced at seven hr following the allergen challenge. Methacholine challenge and sputum induction will be performed 24 hr after allergen challenges. Any adverse events (AEs) and asthma symptoms will be evaluated at each clinic visit. A physical examination, vital signs, ECG, spirometry and laboratory tests will be repeated at the termination visit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
11
AIM-102 is supplied as an oral solution. Dose is 15 mg of AIM-102 per kg of patient weight measured on Treatment Day 1 of each treatment phase The study drug will be administered for 4 consecutive days with at least a 2 week wash-out period prior to crossing over to the alternative treatment for 4 days.
The matching placebo is an oral solution of phosphate buffered saline
McMaster University
Hamilton, Ontario, Canada
Institut de cardiologie et de pneumologie de l'Hôpital Laval
Laval, Quebec, Canada
Change from baseline of the allergen-induced late asthmatic response (LAR) between AIM-102 and placebo.
Spirometry and the presence and severity of asthma symptoms will be assessed immediately before and immediately after each dose. Baseline and allergen-induced methacholine PC20, allergen-induced bronchoconstriction and allergen-induced airway inflammation will be assessed. AUC and maximum decrease in FEV1 for the late response will be compared between treatments using a one-way analysis of variance for the effects of treatment.
Time frame: Pre dose(s) and post dose(s) and 7 and 24 hours post allergen challenge
Early Asthmatic Response
Spirometry \& the presence and severity of asthma symptoms will be assessed immediately before and immediately after each dose. Baseline and allergen-induced methacholine PC20, allergen-induced bronchoconstriction and allergen-induced airway inflammation will be assessed. Allergen-induced increase in airway responsiveness is assessed by measuring the log methacholine PC20 difference from 24 hours before to 24 hours after allergen challenge.
Time frame: Pre-dose(s) and post-dose(s) and 3 hours after allergen challenge
• Comparison of the allergen-induced changes in sputum eosinophils at 7 hr and 24 hr post allergen, between the AIM-102 and placebo
Allergen-induced sputum eosinophils will be compared between treatments using a two-way analysis of variance for the effects of treatment and time.
Time frame: Pre-dose and post-dose(s) and 7 and 24 hours post allergen challenge
Comparison of allergen-induced inflammatory mediators at 7 hr and 24 hr post allergen, between AIM-102 and placebo.
The allergen-induced airway inflammatory cells will be compared between treatments using a two-way analysis of variance.
Time frame: Pre-dose and post-dose(s) and 7 and 24 hours post allergen challenge
Comparison of the allergen-induced airway hyperresponsiveness at 24 hours (hr) post allergen, between AIM-102 and placebo
The allergen-induced airway hyperresponsiveness will be compared between treatments using a one-way analysis of variance for the effects of treatment.
Time frame: Pre-dose and 24 hours post allergen challenge
To determine the pharmacokinetic (PK) profile of AIM-102 in normal healthy mild to moderate asthmatic patients upon repeat dosing of AIM-102
Drug plasma concentration data will be analyzed using a non-compartmental approach to obtain the following PK parameters: * peak plasma concentration * time to peak plasma concentration * elimination rate constant * terminal or elimination half-life * area under the concentration time curve from time 0 to last quantifiable concentration * area under the concentration time curve from time 0, extrapolated to infinity * oral clearance * oral volume of distribution
Time frame: Pre-dose for dosing Days 1, 2, 3, 4, & an optional Day 5, additional samples on Day 3 post-dose & allergen challenge,pre-dose, 1.5, 3, 4.5, 6, & 7.5 hr post-dose
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