Steroids In Eosinophil Negative Asthma

SIENA is a 42-week randomized, stratified, 3-period double-blind placebo-controlled crossover
study of patients with symptomatic mild-to-moderate asthma, not already taking an inhaled
corticosteroid, in whom the effect of "medium-dose" inhaled corticosteroid (ICS) will be
compared with the effect of placebo and with a long-acting muscarinic antagonist (LMA).

Inclusion Criteria:

- Physician-diagnosed asthma for at least previous 12 months.

- Able to perform reproducible spirometry.

- Baseline FEV1≥70% of predicted.

- Asthma confirmed either by:

- Beta-agonist reversibility to 4 puffs albuterol ≥ 12% OR

- Methacholine PC20 ≤ 16 mg/ml

- At least 1 of the following indications for chronic controller therapy:

- Asthma Symptoms > 2 days/week OR

- Nocturnal Asthma Symptoms > 2 nights/month OR

- Short-acting beta-agonist use for symptom control > 2 days/week

- For participants ≥18 years of age: Ability to provide informed consent. For
participants under 18 years of age: Ability to provide verbal or written assent and
ability of parent to provide informed consent.

- Willingness, if female and able to conceive, to utilize one medically-acceptable form
of contraception.

Exclusion Criteria:

- Chronic inhaled or oral corticosteroid therapy.

- Use of inhaled or oral corticosteroid therapy within 6 weeks.

- New allergen immunotherapy within the past 3 months or anticipated changes to an
ongoing immunotherapy regimen.

- Use of omalizumab within 3 months.

- History of:

- bladder-neck obstruction, urinary retention or benign prostatic hyperplasia

- narrow angle glaucoma

- significant cardiovascular disorders and arrhythmias

- life-threatening asthma requiring treatment with intubation or mechanical
ventilation within the past 5 years

- Respiratory tract infection within past 6 weeks.

- History of smoking within the past 1 year, or > 10 pack-years total if ≥ 18 years of
age, or > 5 pack-years total if < 18 years of age.

- Chronic diseases or medical conditions (other than asthma) that could put the
participant at risk by participation, e.g. chronic diseases of the lung (other than
asthma), heart, liver, kidney, endocrine or nervous system, or immunodeficiency.