Comparison of Dry-Powder Inhaler and Pressurized Metered-Dose Inhaler Formulations of Extrafine Beclomethasone Dipropionate/Formoterol Fumarate/Glycopyrronium in Patients with COPD: The TRI-D Randomized Controlled Trial

Figures & data

Figure 1 Study design.

Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; pMDI, pressurized metered-dose inhaler; G, glycopyrronium; DPI, dry-powder inhaler.

Table 1 Baseline Demographics and Disease Characteristics

Parameters	Overall N=366
Age (years)	64.9 (6.9)
Gender, male, n (%)	215 (58.7)
Body mass index (kg/m^2)	27.6 (5.7)
Time since COPD diagnosis (years)	9.5 (6.5)
COPD maintenance medication on study entry, n (%)
ICS/LABA/LAMA	127 (34.7)
ICS/LABA	118 (32.2)
LABA/LAMA	105 (28.7)
LAMA	16 (4.4)
Smoking status, n (%)
Ex-smoker	181 (49.5)
Current smoker	185 (50.5)
Smoking history, (pack-years)	20.0 (6.3)
FEV1 (L)*	1.440 (0.478)
FEV1% predicted*	51.4 (12.2)
FEV1/FVC*	0.48 (0.10)
SGRQ total score^†	44.3 (15.5)
Number of COPD exacerbations in the previous year, n (%)
0	240 (65.6)
1	113 (30.9)
≥2	13 (3.6)

Notes: Data are mean (SD) unless specified otherwise; *Post-bronchodilator; ^†356 patients had data available.

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity.

Figure 2 FEV₁ AUC_0–12h and trough FEV₁ on Day 28 (co-primary endpoints): (A) Change from baseline (ITT population), and (B) treatment contrasts.

Notes: Bars in Panel (A) are adjusted mean changes from baseline and 95% confidence intervals; values in Panel (B) are adjusted mean treatment differences (95% confidence intervals).

Abbreviations: FEV₁, forced expiratory volume in 1 second; AUC, area under the curve; BDP, beclomethasone dipropionate; FF, formoterol fumarate; G, glycopyrronium; DPI, dry-powder inhaler; pMDI, pressurized metered-dose inhaler; ITT, intention to treat; PP, per protocol.

Figure 3 Pre-dose morning FEV₁ and FEV₁ AUC_0–4h on Day 28, and FEV₁ AUC_0–12h on Day 1 (ITT population).

Notes: Bars are adjusted mean changes from baseline and 95% confidence intervals; text is adjusted mean treatment differences (95% confidence intervals).

Abbreviations: FEV₁, forced expiratory volume in 1 second; AUC, area under the curve; BDP, beclomethasone dipropionate; FF, formoterol fumarate; G, glycopyrronium; DPI, dry-powder inhaler; pMDI, pressurized metered-dose inhaler; ITT, intention to treat.

Figure 4 Peak FEV₁ assessed up to 12 h post-dose on Days 1 and 28 (ITT population).

Notes: Bars are adjusted mean changes from baseline and 95% confidence intervals; text is adjusted mean treatment differences (95% confidence intervals).

Abbreviations: FEV₁, forced expiratory volume in 1 second; BDP, beclomethasone dipropionate; FF, formoterol fumarate; G, glycopyrronium; DPI, dry-powder inhaler; pMDI, pressurized metered-dose inhaler; ITT, intention to treat.

Table 2 Rescue Medication Use (ITT Population)

	BDP/FF/G DPI (N=354)	BDP/FF/G pMDI (N=357)	BDP/FF pMDI (N=357)
Rescue-free days, %	70.6 (68.9, 72.2)	68.9 (67.3, 70.5)	65.3 (63.7, 66.9)
BDP/FF/G DPI vs BDP/FF/G pMDI	1.64 (–0.61, 3.89); p=0.154
vs BDP/FF pMDI	5.25 (3.01, 7.49); p<0.001	3.61 (1.36, 5.86); p=0.002
Average use of rescue medication, puffs/day	0.753 (0.685, 0.821)	0.736 (0.668, 0.803)	0.902 (0.836, 0.968)
BDP/FF/G DPI vs BDP/FF/G pMDI	0.017 (–0.077, 0.112); p=0.723
vs BDP/FF pMDI	–0.149 (–0.243, –0.055); p=0.002	–0.166 (–0.261, –0.072); p<0.001

Note: Data are adjusted mean or adjusted mean difference (95% confidence interval).

Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; G, glycopyrronium; DPI, dry-powder inhaler; pMDI, pressurized metered-dose inhaler.

Figure 5 SGRQ total and domain scores on Day 28 (ITT population).

Notes: Bars are adjusted mean changes from baseline and 95% confidence intervals; text is adjusted mean treatment differences (95% confidence intervals).

Abbreviations: FEV₁, forced expiratory volume in 1 second; BDP, beclomethasone dipropionate; FF, formoterol fumarate; G, glycopyrronium; DPI, dry-powder inhaler; pMDI, pressurized metered-dose inhaler; ITT, intention to treat.

Table 3 Adverse Events, Overall and Most Common Preferred Terms (≥1% of Patients with Any Treatment for Adverse Events; ≥2 Patients in Any Group for Drug-Related Adverse Events, Serious Adverse Events, and Severe Adverse Events)

Number of patients (%)	BDP/FF/G DPI (N=354)	BDP/FF/G pMDI (N=358)	BDP/FF pMDI (N=357)
Adverse events	55 (15.5)	67 (18.7)	55 (15.4)
COPD exacerbation	12 (3.4)	13 (3.6)	7 (2.0)
Nasopharyngitis	10 (2.8)	9 (2.5)	11 (3.1)
Headache	4 (1.1)	7 (2.0)	2 (0.6)
Back pain	0	4 (1.1)	3 (0.8)
Treatment-related adverse events	3 (0.8)	3 (0.8)	7 (2.0)
Dry mouth	2 (0.6)	0	1 (0.3)
Severe adverse events	5 (1.4)	6 (1.7)	3 (0.8)
Pneumonia*	1 (0.3)	2 (0.6)	0
Severe treatment-related adverse events	0	0	1 (0.3)
Serious adverse events	4 (1.1)	6 (1.7)	1 (0.3)
Pneumonia*	1 (0.3)	2 (0.6)	0
COPD exacerbation	0	2 (0.6)	1 (0.3)
Serious treatment-related adverse events	0	0	0
Adverse events leading to study treatment discontinuation	1 (0.3)	5 (1.4)	1 (0.3)
Pneumonia*	0	2 (0.6)	0
Adverse events leading to death	0	1 (0.3)	0

Notes: *Note that there was one pneumonia adverse event in one patient receiving BDP/FF/G DPI, which was considered severe in intensity and serious, but did not result in study discontinuation. Two patients receiving BDP/FF/G pMDI experienced one pneumonia adverse event each, both severe in intensity and serious, and resulted in study discontinuation.

Abbreviations: BDP, beclomethasone dipropionate; FF, formoterol fumarate; G, glycopyrronium; DPI, dry-powder inhaler; pMDI, pressurized metered-dose inhaler; COPD, chronic obstructive pulmonary disease.