Regulatory Decision Summary for Aridol

Asthma is a chronic disease of the lungs characterized by airway inflammation, bronchoconstriction and increased airway responsiveness. The diagnosis of asthma requires clinician judgment based on the constellation of symptoms and physiological tests of the airways. Aridol is intended for the assessment of bronchial hyperresponsiveness in patients who do not have clinically apparent asthma.

The effectiveness of Aridol in assessing bronchial hyperresponsiveness to aid in the diagnosis of adults and children 6 years of age and older was assessed in two clinical studies. Study 1 was an operator-blinded, open-label crossover trial that assessed the sensitivity (i.e. the ability of a test to correctly identify those with the disease) and specificity (i.e. the ability of a test to correctly identify those without the disease) of bronchial challenge testing with Aridol compared with a methacholine bronchial challenge test in detecting bronchial hyperresponsiveness in subjects with symptoms suggestive of asthma but without a definite diagnosis of asthma. Five hundred and nine subjects aged 6 to 50 years were screened for enrolment with 419 and 420 subjects receiving at least one dose of mannitol, the active ingredient in Aridol, or methacholine, respectively. In study 1, Bronchial challenge testing with Aridol and methacholine demonstrated similar sensitivity and specificity in predicting bronchial hyperresponsiveness defined by a positive exercise challenge.

Study 2 was a crossover study comparing bronchial challenge testing with Aridol to hypertonic (4.5%) saline in identifying bronchial hyperresponsiveness in subjects 6 to 83 years of age with (n=551) and without (n=95) asthma. In this study the efficacy endpoint of interest was an estimation of the sensitivity and specificity of bronchial challenge testing with Aridol with respect to a physicians clinical diagnosis of asthma. In study 2, the sensitivity of the Aridol bronchial challenge test in subjects with asthma was 58% compared to a sensitivity of the physician diagnosis in the same population of 97%. The specificity of the Aridol bronchial challenge test in subjects without asthma was 95% compared to the specificity of the physician diagnosis of 98%.

No serious adverse reactions were reported following bronchial challenge testing with Aridol in either trial. Most patients experienced cough during the challenge; however, it was only occasional in the majority of these patients (87%). In the remainder, it was frequent enough to cause some delay in continuation of the challenge (13%) or discontinuation (1%). Oropharyngeal pain was also a commonly reported adverse reaction. Mannitol, the active ingredient in Aridol, may cause severe bronchospasm in susceptible subjects. A positive result with Aridol may produce symptoms of bronchospasm such as chest tightness, cough or wheezing. To address the concern of a possible bronchospasm, a box warning was added to the product monograph warning and instructing health care professionals on how to mitigate this risk (e.g. medications to treat severe bronchospasm such as short acting inhaled beta agonists must be present in the testing area, the test should be conducted under the supervision of a physician familiar with the management of acute bronchospasm).

The 50-60% sensitivity and specificity observed reveals that there are uncertainties when using Aridol for asthma diagnosis. It is important to note that the sensitivity and specifity of Aridol is similar to that of methacholine, a previously approved drug currently used in similar circumstances. An Aridol test should be conducted under the supervision of trained Health Care Professionals as part of an overall assessment of asthma and not as a stand-alone or screening test for asthma.