Table 1.
Characteristics of the Clinical Studies Included in the Systematic Review
| Study and Year | ClinicalTrials.gov Identifier and/or Company ID | Study Characteristics | Treatment Duration (Days) | Number of Analyzed Patients | Drugs, Doses, and Regimen of Administration | Comparator | Route of Administration | Inhaler Device | Patient Characteristics | Age (Years) | Male (%) | Current Smokers (%) | Smoking History (Pack-Years) | BMI (kg/m2) | Pre-Bronchodilator FEV1 Predicted (%) | Investigated Outcomes | Jadad Score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Brown et al, 201943,44 | NCT02479412 | Phase IIa, multicenter, randomized, double-blind, 3-period, placebo-controlled, incomplete-block, crossover | 15 | 54 | AZD7594 58 μg (q.d.), 250 μg (q.d.), 800 μg (q.d.) | Placebo (q.d.) | Oral inhalation | DPI | Mild to moderate asthmatic (pre-bronchodilator FEV1 ≥40% and ≤90% of predicted, FENO ≥25 ppb) | 50.8 | 82.9 | 0.0 | NA | 27.3 | ≥40.0 and ≤90.0 | Lung function, symptom control, PK, PD, and safety | 5 |
| Prothon et al, 201945,46 | NCT02645253 | Phase I, single-center, randomized, single-blind, placebo-controlled, sequential-group | 20 | 27 | AZD7594 200 μg (q.d.), 400 μg (q.d.), 1600 μg (q.d.) | Placebo (q.d.) | Oral inhalation | DPI | Healthy Japanese subjects (NA) | 34.0 | 100.0 | NA | NA | 23.1 | NA | PK, PD, and safety | 3 |
| Melin et al, 201747,48 | NCT01310322, Study A | Phase I, single-center, partly randomized, open-label, 4-way, crossover | 1 | 13 | AZD5423 250 μg, 420 μg, 450 μg, 1200 μg (single dose) | NA | AZD5423 420 μg, 450 μg: oral inhalation, AZD5423 250 μg: IV, AZD5423 1200 μg: PO | Jet nebulizer, hand-held vibrating mesh nebulizer | Healthy subjects (NA) and mild allergic asthmatic (pre-bronchodilator FEV1 ≥70%) | 18.0–42.0 | 100.0 | 0.0 | NA | 20.5–28.4 | ≥70.0 | PK and safety | 1 |
| Melin et al, 201748,49 | NCT01635985, Study B | Phase I, single-center, partly randomized, open-label, 6-way, crossover | 1 | 18 | AZD5423 250 μg, 332 μg, 405 μg, 456 μg, 523 μg, 1200 μg (single dose) | NA | AZD5423 332 μg, 405 μg, 456 μg, 523 μg: oral inhalation, AZD5423 250 μg: IV, AZD5423 1200 μg: PO | Jet nebulizer, hand-held vibrating mesh nebulizer, approved DPI, new DPI |
Healthy subjects (NA) | 21.0–40.0 | 100.0 | 0.0 | NA | 19.2–30.0 | NA | PK and safety | 1 |
| Chen et al, 201751,52 | NCT02648438 | Phase I, single-center, partiy randomized, open-label, 4-period, parallel | 1 | 30 | AZD7594 150 μg, 400 μg, 1200 μg | NA | AZD7594 400 μg: oral inhalation, AZD7594 150 μg: IV, AZD7594 1200 μg: PO | Mono-dose DPI, MDI | Healthy subjects (NA) | 32.9 | 100.0 | 0.0 | NA | 18.0–30.0 | NA | PK and safety | 1 |
| Werkström et al, 201650 | NA, Study A | Single-dose Phase I, single-center, randomized, double-blind, placebo-controlled, escalated-dose | 1 | 59 | AZD5423 8.4–2400 μg | Placebo | Oral inhalation | Jet nebulizer | Healthy subjects (NA) | 26.0 | 100.0 | NA | NA | 24.0 | NA | PK, PD, and safety | 2 |
| Werkström et al, 201650 | NA, Study B | Multiple-ascending dose Phase I, randomized, double-blind, placebo-controlled, parallel | 14 | 27 | AZD5423 125 μg (q.d.), 375 μg (q.d.), 499 μg (q.d.) | Placebo | Oral inhalation | Jet nebulizer | Healthy subjects (NA) | 28.0 | 100.0 | NA | NA | 25.0 | NA | PK, PD, and safety | 2 |
| Werkström et al, 201650 | NA, Study C | Single- and multiple-ascending dose Phase I, single-center, randomized, double-blind, placebo-controlled, parallel | 14 | 30 | AZD5423 50 μg (single-dose), 100 μg (q.d.), 300 μg (q.d.) | Placebo | Oral inhalation | Hand-held vibrating mesh nebulizer | Healthy Japanese subjects (NA) | 29.6 | 100.0 | NA | NA | 22.2 | NA | PK, PD, and safety | 2 |
| Leaker et al, 201553 | NCT00483899, Part B | Phase II, multicenter, randomized, double-blind, placebo-controlled, 3-way, crossover | 21 | 21 | GW870086X 1 mg (q.d.), 3 mg (q.d.) | Placebo | Oral inhalation | DPI | Mild asthmatic (pre-bronchodilator FEV1 ≥60% of predicted, FENO ≥25 ppb) | 28.0 | 100.0 | NA | NA | 24.0 | 87.0 | Lung function, PK, PD, and safety | 3 |
| Gauvreau et al, 201554,55 | NCT01225549 | Phase II, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled, 4-way, crossover | 7 | 20 | AZD5423 75 μg (q.d.), 300 μg (q.d.), and BUD 200 μg (b.i.d.) | Placebo | Oral inhalation | AZD5423: vibrating mesh nebulizer I-neb®, BUD: DPI (Turbuhaler®) | Mild atopic asthmatic (pre-bronchodilator FEV1 ≥70% of predicted, NA) | 29.6 | 55.0 | 0.0 | NA | NA | 92.1 | Lung function, PD, and safety | 4 |
| Bareille et al, 201356,57 | NCT00945932 | Phase II, multicenter, randomized, double-blind, placebo-controlled, 2-way crossover | 28 | 36 | GW870086X 1 mg (q.d.) | Placebo | Oral inhalation | DPI (Diskhaler®) | Mild to moderate asthmatic (pre-bronchodilator FEV1 ≥40% and ≤85% of predicted) | 49.0 | 56.0 | 0.0 | ≤10.0 | 26.0 | 73.7 | Lung function, and safety | 4 |
| Allen et al, 201358,59 | NCT01160003, SIG113209 | Dose-ascending, Phase I, single-center, randomized, double-blind, placebo-controlled, 3-way crossover | 14 | 12 | GW870086X 5 mg (q.d.), 8.75 mg (q.d.) | Placebo | Oral inhalation | Nebulizer (NA) | Healthy subjects (NA) | 54.0 | 100.0 | 0.0 | >5.0 | 24.5 | NA | PK, PD, and safety | 3 |
| Bareille et al, 201360,63 | NCT01245426, SIG114749 | Phase II, multicenter, randomized, double-blind, placebo-controlled, parallel | 27 | 135 | GW870086X 2 mg (q.d.), 4 mg (q.d.), 3 mg (q.d. added at interim) | Placebo | Oral inhalation | NA | Persistent asthmatic (pre-bronchodilator FEV1 ≥60% and <85% of predicted) | 43.5 | 80.7 | 0.0 | ≤10.0 | 25.4 | NA | Lung function, and safety | 5 |
| Bareille et al, 201361,64 | NCT00857857, SIG110762 | Phase IIa, multicenter, randomized, double-blind, placebo- and active-controlled, incomplete block, 3-way crossover | 13 | 24 | GW870086X 0.25 mg (q.d.), 1 mg (q.d.), 3 mg (q.d.), and FP 0.25 mg (b.i.d.) | Placebo | Oral inhalation | DPI | Mild asthmatic (pre-bronchodilator FEV1 >65% of predicted) | 39.4 | 100.0 | 0.0 | ≤10.0 | NA | >65.0 | Lung function, PD, and safety | 5 |
| Boulet et al, 200962 | NA | Dose-ascending, Phase I, multicenter, randomized, double-blind, escalated-dose | 21 | 26 | TPI 1020 600 μg (b.i.d. for 2 weeks), 1200 μg (b.i.d. for 1 week), BUD 400 μg (b.i.d. for 2 weeks), 800 μg (b.i.d. for 1 week) | NA | Oral inhalation | DPI | Mild asthmatic (pre-bronchodilator FEV1 ≥75% of predicted) | 34.4 | 51.9 | 100.0 | 10.8 | NA | 85.3 | PK, PD, and safety | 3 |
Abbreviations: b.i.d., twice daily; BMI, body mass index; BUD, budesonide; DPI, dry powder inhaler; FENO, fraction exhaled of nitric oxide; FEV1, forced expiratory volume in 1 second; FP, fluticasone propionate; IV, intravenous administration; MDI, metered-dose inhaler; NA, not available; PD, pharmacodynamics; pMDI, pressurized metered-dose inhaler; PO, oral administration; PK, pharmacokinetics; ppb, parts per billion; q.d., once daily.