Table 3.
Summary of studies demonstrating clinical efficacy with extrafine beclomethasone/formoterol in chronic obstructive pulmonary disease
| Study | Subjects | Treatment | Design, duration | Assessment | Results |
|---|---|---|---|---|---|
| Tzani et al.[27] | 20 patients with COPD | BDP-FF 400/24 mcg FP-S 500/100 mcg |
Double-blind, double dummy, randomized, parallel group 12 week | FRC, RV, TLC, FVC, FRC/TLC, RV/TLC, TDI | Improvement in postdose RV/TLC % versus baseline: BDP-FF (58.22±4.69) to (−4.76±2.35) > FP-S (64.00±2.29) to (0.65±2.35) Trend toward improvement only in BDP-FF Improvement in postdose RV versus baseline: BDP-FF (4.73±0.76) to (−0.77±0.29) > FP/S (4.82±0.28) to (0.14±0.29) (P<0.05) Improvement in TDI total score: Clinically relevant improvement versus baseline (1.144) seen only in BDP-FF group (P=0.026) not in FP-S group |
| Singh et al.[29] | 419 patients; moderate/severe COPD | BDP-FF 200/12 mcg FP-S 500/50 mcg bid |
Multicentre, randomised, double-blind, double dummy 12 week | Primary: TDI score, change from predose FEV1 in 30 min Secondary: PFT, symptom free days, reliever use, SGRQ, symptom score, COPD-6, exacerbations |
Equivalence in TDI score: (44.1% patients) BDP-FF group and (43.0% patients) FP-S group had a≥1 improvement in TDI score (P=0.92) Improvement in postdose FEV1 at 5, 15, 30 min: BDP-FF group>FP-S group at all time points (P<0.001) Improvement in SGRQ score: Clinically relevant improvement>4 units in BDP-FF group but not in FP-S group |
| De Backer et al.[28] | 27 patients stage II to IV COPD | BDP-FF (100/6 mcg) 2 inhalations, bid | Prospective, open-label, 24 weeks | Primary: siVaw, siRaw, siRaw, FEV1, FVC, PEF, MEF50, MEF25.VC, IVC, FRC, TLC, Raw, SGaw Secondary: MMRC SGRQ |
Deposition (recorded by CFD): 11% lesser extrathoracic deposition versus nonextrafine formulation 4% increase in lobe deposition with extrafine BDP-FF Improvement in FEV1% pred versus baseline: 4-6 h after administration 46±14% to 50±15% (P=0.0003) Hyperinflation: Reduction in FRC of 7±10% pred (P 0.002) |
| Forward study Wedzicha et al.[30] | 1186 patients; severe COPD | BDP-FF 400/24 mcg, versus F 24 mcg | Randomised, double-blind, parallel-group; 48 weeks | Primary: Exacerbation rate, change in predose morning FEV1 (L) from baseline (randomisation visit) to week 12 Secondary: Time to first COPD exacerbation, (SGRQ) |
Percentage of patients with exacerbations: BDP-FF group: (44.4%) F group: (49.7%) Mean FEV1 change at week 12: BDP-FF > F group (0.081 L versus 0.012 L, P<0.001) |
| Calverley et al.[31] | 718 patients; severe but stable COPD | BDP-FF (200/12 mcg) BUD-F (400/12 mcg) F (12 mcg) |
Double-blind, double-dummy, randomised, active-controlled, parallel-group 48 weeks | Primary: Change in predose morning FEV1 from baseline to 48 weeks, mean rate of COPD exacerbations Secondary: Dyspnoea score, SGRQ score |
Improvement in predose morning FEV1: 0.077 L, 0.080 L and 0.026 L for BDP-FF, BUD-F and F, respectively Exacerbation rate: 0.414 per patient per year in BDP-FF group; 0.423 in BUD-F group; 0.431 in the F group Reduction in dyspnoea score: BDP-FF (-0.19±0.74) versus baseline and BUD-F (-0.18±0.78) versus baseline; F (-0.07±0.76) versus baseline |
siVaw: Airway volumes specific for the lung volume, siRaw: Specific airway resistance, iVlobes_FRC: Lobar volumes at FRC, iVlobes_TLC: Lobar volumes at total lung capacity, Raw: Airway resistance, SGaw: Specific airway conductance, SGRQ: St. George’s Respiratory Questionnaire, TDI: Transition Dyspnoea Index, COPD: Chronic obstructive pulmonary disease, BDP-FF: Beclomethasone/formoterol, FRC: Functional residual capacity, RV: Residual volume, TLC: Total lung capacity, FVC: Forced vital capacity, TDI: Transition dyspnea index, FEV1: Forced expiratory volume in 1 s, PFT: Pulmonary function test, CFD: Computational fluid dynamics, BUD-F: Budesonide-formoterol, IVC: Inspiratory vital capacity