Selective β2-AR Antagonism in Asthma

Inclusion Criteria: * Men or women * Minimum 21 years old * History of mild-to-moderate asthma for at least 6 months and controlled by an inhaled SABA, as required * Otherwise healthy * Ideally have participated in previous asthma studies * No corticosteroid for whatever reason within 8 weeks of the start of dosing * No other prescription medicine within 28 days (apart from a short acting beta-agonist (SABA) or contraceptives in women) * No over-the-counter medicine within 7 days (apart from acetaminophen) before the start of dosing * Negative screen for drugs of abuse; forced expiratory volume in 1 second (FEV1) more than or equal to 70% predicted * Fractional exhaled nitric oxide (FeNO) more than or equal to 35 ppb * 15% fall in FEV1 after inhaled mannitol (PD15) * Non-smoker or past smoker (\<5 pack years) * Substitution of subject's SABA inhaler with an anti-cholinergic inhaler, ipratropium bromide, for use as a reliever or rescue medication during a run-in period and during dosing with TR4 or placebo. Exclusion Criteria: * Positive test for hepatitis B \& C or HIV * Drug or alcohol abuse * Airway infection or asthma exacerbation in the last 4 weeks * Current seasonal asthma * History of emergency treatment of asthma * Loss of more than 400 mL blood, or participation in other clinical trials of unlicensed medicines within the previous 3 months * Consumption of grapefruit or herbal remedies within the past 7 days * Objection by the subject's general practitioner (GP) * …