To update the CTCAE (common terminology criteria for adverse events) version number, used for grading adverse events per FDA request. To avoid interference from bronchodilator medicines subjects were asked, where feasible, to withhold their normal morning asthma medications on days on which they attended the site for measurements of spirometry and FeNO until these measurements were complete. The eligibility criteria were amended to include only subjects with serum IgE <500 IU/mL.

This protocol was amended in response to feedback from investigators. The amendment included some study restrictions such as avoiding nitrate rich foods prior to measurements of fractional exhaled nitric oxide (FeNO) and withholding long- and short-acting antihistamines prior to the skin prick testing. The requirement to avoid nitrate-rich food prior to measurement of FeNO was provided in a separate manual and the requirement to withhold antihistamines was included in the published guidelines that were referenced in the protocol.

Feedback from investigators suggested that a significant proportion of the target population with uncontrolled asthma presented with Asthma Control Questionnaire (ACQ) scores between ≥ 1.5 and 2.0, and a significant proportion was between the age of 65 and 75 years. In order to allow this population to enter the trial, the eligibility criterion for baseline ACQ score will be changed from > 2.0 to ≥ 1.5 and the upper age limit will be increased from 65 years to 75 years.

This protocol was amended primarily to increase the planned enrollment of the study to enable inclusion of a sufficient number of subjects for efficacy analyses in one or more subpopulations. The study enrollment was therefore increased to approximately 84 subjects randomized with an aim of at least 72 subjects completing the study. This expansion of the enrollment target ensured meaningful efficacy analysis.