Table 2.
Phase II dose finding and safety trials
| Authors | Year | Main inclusion criteria | Age | Number | Treatment | Duration | Primary outcome | Secondary outcomes | Conclusions |
|---|---|---|---|---|---|---|---|---|---|
| Vogelberg C et al. [123] | 2015 | FEV1 60–90%pred. Symptomatic with ACQ-7 > 1.5 and treatment with 200–400 μg of budesonide or eq. +/− LABA +/− LTRA | 6–11 | 101 | Add on tiotropium 1.25 μg, 2.5 μg, 5 μg or placebo to medium-dose ICS with or without LTRA | 12 weeks | Peak FEV1(0–3 h) | 1) Trough FEV1
2) Trough FVC 2) FEV1AUC (0–3h) 3) morning/evening PEF 4) ACQ-7 5) PAQLQ (S) |
All doses were superior to placebo in all outcomes. No difference between doses. |
| Vogelberg C et al. [124] | 2014 | FEV1 60–90%pred. Symptomatic with ACQ-7 > 1.5 | 12–17 | 105 | Add on tiotropium 1.25 μg, 2.5 μg, 5 μg or placebo to medium-dose ICS with or without LTRA |
4 weeks | Peak FEV1(0–3 h) | 1) Trough FEV1
2) FEV1AUC (0–3h) 3) Morning/evening PEF 4) ACQ-7 |
The response of Tiotropium 5 μg dose is superior compared to placebo and greater than tiotropium 1.25 and 2.5 μg |
| Kerstjens HA et al. [125] | 2011 | Severe persistent asthma FEV1 < 80%pred. ACQ-7 > 1.5 and high dose ICS (≥800 μg budesonide or eq.) + LABA +/− teophylline, LTRA or OCS |
18–75 | 100 | Add on tiotropium 5 μg vs 10 μg vs placebo | 24 weeks | Peak FEV1(0–3 h) | 1) Trough FEV1
2) Peak FVC 3) FVC AUC (0–3h) 4) Trough FVC 5) FEV1AUC (0–3h) 6) morning/evening PEF 7) Mini AQLQ 8) rescue medication use 9) asthma symptoms 10) symptom free days |
Compared with placebo, both tiotropium doses were superior in all outcomes. There was no difference between doses. |
| Beeh KM et al. [128] | 2014 | FEV1 60–90%pred. Symptomatic with ACQ-7 > 1.5 and medium dose ICS +/− LABA +/− SABA |
18–75 | 141 | Add on tiotropium 1.25 μg vs 2.5 μg vs 5 μg vs placebo | 12 weeks | Peak FEV1(0–3 h) | 1) Trough FEV1
2) Peak FVC (0–3 h) 3) FVC AUC (0–3h) 4) Trough FVC 5) FEV1AUC (0–3h) 6) morning/evening PEF 7) ACQ 7 |
Compared with placebo, all tiotropium doses were superior in all outcomes. The largest response was obtained with 5 μg |
| Timmer W et al. [127] | 2015 | FEV1 60–90%pred. Symptomatic with ACQ-7 > 1.5 and medium dose ICS +/− LABA +/− SABA |
18–75 | 89 | Add on tiotropium 5 μg OD vs 2.5 μg BID vs placebo | 12 weeks | FEV1AUC (0–24) | 1) Peak FEV1 (0–24 h) 2) Trough FEV1 3) morning/evening PEF 4) ACQ-7 |
Both tiotropium doses are superior to placebo in all outcomes. No advantage of BID administration. |
| Ohta K et al. [129] | 2015 | FEV1 60–90%pred. Symptomatic despite 400–800 μg budesonide or eq. +/− LABA |
18–75 | 285 | Add on tiotropium 2.5 μg, 5 μg or placebo to ICS +/− maintenance therapy | 52 weeks | Long term safety | 1) Trough FEV1
2) Trough FVC 3) Trough PEF 4) ACQ-7 |
No difference in AEs rate between groups |
Phase II dose finding and safety trials performed with tiotropium in patients with poorly controlled moderate and severe asthma. N number of patients randomized to treatment, %pred percent predicted, eq. equivalent, AQLQ Asthma Quality of Life Questionnaire, PAQLQ Pediatric Asthma Quality of Life Questionnaire, OCS oral corticosteroids. For other abbreviations please see text