Table 1 Key inclusion and exclusion criteria for participation in the SYGMA programme

• Male and female outpatients aged ≥12 years

• A documented clinical history of asthma for at least 6 months prior to visit 1, diagnosed according to GINA criteria

• Patients in need of GINA (2012) step 2 treatment for the last 30 days before visit 2, i.e. patients with asthma that is either:

 • Well-controlled on mono-maintenance therapy with either a low, stable dose of an ICS or a LTRA in addition to as-needed use of inhaled short-acting bronchodilator(s) (SABA and/or short-acting anticholinergic agent)

 • Uncontrolled on inhaled short-acting bronchodilator(s) as needed (SABA and/or short-acting anticholinergic agent)

• Lung function tests at visit 2 (according to the ERS guidelines [38]); patients pre-treated with:

 • Low-dose ICS or LTRA in addition to inhaled short-acting bronchodilator(s) should have pre-bronchodilator FEV₁ ≥ 80%

 • An inhaled short-acting bronchodilator only should have pre-bronchodilator FEV₁ ≥ 60% predicted and post-bronchodilator FEV₁ ≥ 80% predicted

• Reversible airway obstruction at visit 2, defined as an increase in FEV₁ ≥ 12% and 200 mL relative to baseline, after inhalation of 1 mg terbutaline Turbuhaler®. The test can be repeated at visit 3 in case patients fail at visit 2. If patients fail at both occasions, they can still be included if they have documented historical reversibility within the last 12 months prior to visit 3, with an increase in FEV₁ ≥ 12% and 200 mL relative to baseline after administration of a rapid-acting β₂-agonist

• For randomisation at visit 3, patients should fulfil the following criteria:

 • Use of as-needed terbutaline Turbuhaler® due to asthma symptoms on at least 3 separate days during the last week of the run-in period

 • Ability to use Turbuhaler® correctly and to complete the eDiary correctly. Morning and evening data must be recorded for at least 8 days (any 8) of the last 10 days of the run-in period

• Any asthma worsening requiring change in asthma treatment other than SABA and/or short-acting anticholinergic agent within 30 days prior to visit 1 or during run-in

• Use of oral, rectal or parenteral GCS within 30 days and/or depot parenteral GCS within 12 weeks prior to visit 1

• Smoker (current or previous) with a smoking history of ≥10 pack years

• Use of any β-blocking agent, including eye drops

• Any significant disease or disorder (e.g. cardiovascular, gastrointestinal, hepatic, renal)

• Pregnancy, breast-feeding or planned pregnancy

• For randomisation at visit 3, patients should not fulfil any of the following criteria:

 • Use of ≥6 terbutaline Turbuhaler® as-needed inhalations per day, for a certain number of days depending on the actual length of run-in: for ≥2 days out of 14 days; for ≥3 days out of 15–21 days; for ≥4 days out of 22 or more days of run-in