ClinicalTrials.gov identifier | NCT01634113 | NCT01634139 | NCT01634152 | NCT01257230 | NCT01277523 |
Phase and design# | Phase 2/3 | Phase 3, randomised, double-blind, placebo-controlled, parallel-group | Phase 3, randomised, double-blind, placebo-controlled, parallel-group | Phase 3, randomised, double-blind, placebo-controlled, parallel-group | Phase 3, randomised, double-blind, placebo-controlled, parallel-group |
Objectives | Efficacy and safety | Efficacy and safety | Efficacy and safety | Efficacy and safety | Efficacy and safety |
Patient population | 1–5-year-olds with persistent asthmatic symptoms | 6–11-year-olds with symptomatic moderate asthma | 6–11-year-olds with symptomatic severe asthma | 12–17-year-olds with symptomatic moderate asthma | 12–17-year-olds with symptomatic severe asthma |
History of asthma | NA | ≥6 months | ≥6 months | ≥3 months | ≥3 months |
Symptomatic asthma | Daytime symptoms more than twice a week; any limitation of activities; any nocturnal symptoms/awakenings; need for rescue medication >2 days·week−1 | ACQ-IA ≥1.5 | ACQ-IA ≥1.5 | ACQ ≥1.5 | ACQ ≥1.5 |
Minimum asthma controller medication | Stable ICS, with or without another controller, for ≥4 weeks before screening | Medium-dose ICS (200–400 μg·day−1 budesonide or equivalent dose), with or without another controller, for ≥4 weeks before screening; LABA had to be discontinued ≥24 h prior to screening | High-dose ICS (>400 μg·day−1 budesonide or equivalent dose) plus ≥1 controller or medium-dose ICS (200–400 μg·day−1 budesonide or equivalent dose) plus ≥2 controllers for ≥4 weeks before screening | Medium-dose ICS (400–800 μg·day−1 budesonide or equivalent dose), with or without LTRA, for ≥4 weeks before screening; LABA had to be discontinued ≥72 h prior to screening | High-dose ICS (800–1600 μg·day−1 budesonide or equivalent dose) plus ≥1 controller or medium-dose ICS (400–800 μg·day−1 budesonide or equivalent dose) plus ≥2 controllers for ≥4 weeks before screening |
Pre-bronchodilator FEV1 % pred at screening | ≤90% for 5-year-olds | 60–90% | 60–90% | 60–90% | 60–90% |
FEV1 reversibility at screening | | ≥12%, 15–30 min after 200 μg salbutamol | ≥12%, 15–30 min after 200 μg salbutamol | ≥12% and ≥200 mL, 15–30 min after 400 μg salbutamol (age >14 years) or ≥12% only (age 12–14 years) | ≥12% and ≥200 mL, 15–30 min after 400 μg salbutamol (age >14 years) or ≥12% only (age 12–14 years) |
Variability of absolute FEV1 from screening to randomisation¶ | | ±30% | ±30% | ±30% | ±30% |
Smoking history | | | | Nonsmoker or ex-smoker who stopped smoking ≥1 year prior to enrolment | Nonsmoker or ex-smoker who stopped smoking ≥1 year prior to enrolment |
Exclusion criteria | Significant disease other than asthma | Significant disease other than asthma | Significant disease other than asthma | Significant disease other than asthma | Significant disease other than asthma |
Treatment | Once-daily tiotropium (5 or 2.5 µg) or placebo+ | Once-daily tiotropium (5 or 2.5 µg) or placebo | Once-daily tiotropium (5 or 2.5 µg) or placebo | Once-daily tiotropium (5 or 2.5 µg) or placebo | Once-daily tiotropium (5 or 2.5 µg) or placebo |
Treatment duration | 12 weeks | 48 weeks | 12 weeks | 48 weeks | 12 weeks |
Sample size | 102 randomised patients (101 treated, 102 planned); 101 completed patients | 403 randomised patients (401 treated, 385 planned); 384 completed patients | 401 randomised patients (400 treated, 375 planned); 392 completed patients | 398 randomised patients (397 treated, 127 planned per group); 376 completed patients | 392 randomised patients (392 treated, 375 planned); 388 completed patients |