A randomized study using functional respiratory imaging to characterize bronchodilator effects of glycopyrrolate/formoterol fumarate delivered by a metered dose inhaler using co-suspension delivery technology in patients with COPD

Figures & data

Figure 1 Patient disposition diagram.

Abbreviations: GFF, glycopyrrolate/formoterol fumarate; h, hours; MDI, metered dose inhaler.

Figure 2 Study design.

Abbreviations: GFF, glycopyrrolate/formoterol fumarate; TP, treatment period; MDI, metered dose inhaler; HRCT, high-resolution computed tomography.

Table 1 Demographics and baseline characteristics (safety/intent-to-treat population)

Parameters	Total (N=20)a
Age (years), mean (SD); min–max	64.8 (8.7); 46–78
Male, n (%)	15 (75)
Body mass index (kg/m^2), mean (SD)	26.3 (3.1)
Moderate/severe COPD, n (%)	17 (85)/3 (15)
Duration of COPD (years), mean (SD); min–max	6.1 (4.5); 0.2–15.6
Number of pack-years smoked,b mean (SD)	51.3 (41.4)
Pre-bronchodilator FEV1 at screening (%),mean predicted (SD)	53.9 (11.4)
Post-bronchodilator FEV1 at screening (%),mean predicted (SD)	60.1 (11.4)
Pre-bronchodilator FEV1 at screening (L), mean (SD)	1.63 (0.51)
Post-bronchodilator FEV1 at screening (L), mean (SD)	1.82 (0.56)
Pre-dose FEV1 at baseline (L), mean (SD)c	1.59 (0.56)

Notes:

a Only 19 patients were included in the efficacy analyses, as one patient withdrew early (due to a treatment-emergent adverse event of tremor) prior to any post-dose high-resolution computed tomography scans being performed.

b Number of pack-years smoked = (number of cigarettes per day/20)×number of years smoked.

c Baseline was defined as the mean of available pre-dose values from both treatment periods.

Abbreviations: FEV₁, forced expiratory volume in 1 second; max, maximum; min, minimum.

Figure 3 Functional respiratory imaging co-primary endpoint: siVaw at TLC on Day 15 (mL/L; intent-to-treat population).

Note: Images from one representative patient.

Abbreviations: GFF, glycopyrrolate/formoterol fumarate; LSM, least squares mean; MDI, metered dose inhaler; siVaw, specific image-based airway volume; TLC, total lung capacity.

Figure 4 Functional respiratory imaging co-primary endpoint: siRaw at TLC on Day 15 (kPa⋅s; intent-to-treat population).

Note: Images from one representative patient.
Abbreviations: GFF, glycopyrrolate/formoterol fumarate; LSM, least squares mean; MDI, metered dose inhaler; siRaw, specific image-based airway resistance; TLC, total lung capacity.

Figure 5 Spirometry endpoints on Day 15: change from baseline in post-dose FEV₁, IC, and FVC (intent-to-treat population).

Note: Error bars and parentheses represent 95% CIs.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GFF, glycopyrrolate/formoterol fumarate; IC, inspiratory capacity; LSM, least squares mean; MDI, metered dose inhaler.

Figure 6 Scatter plot comparison of change from baseline in siVaw (A) and siRaw (B) with change from baseline in FEV₁ at Day 15.

Abbreviations: FEV₁, forced expiratory volume in 1 second; GFF, glycopyrrolate/formoterol fumarate; MDI, metered dose inhaler; siRaw, specific image-based airway resistance; siVaw, specific image-based airway volume.

Figure 7 Body plethysmography endpoints on Day 15: ratio to baseline in post-dose FRC, RV, and TLC (intent-to-treat population).

Note: Error bars and parentheses represent 95% CIs.
Abbreviations: FRC, functional residual capacity; GFF, glycopyrrolate/formoterol fumarate; LSM, least squares mean; MDI, metered dose inhaler; RV, residual volume; TLC, total lung capacity.

Table 2 Summary of AEs (safety population)

Parameters	GFF MDI (n=20)	Placebo MDI (n=19)	Total (N=20)
At least one TEAE	12 (60.0) [19]	8 (42.1) [14]	15 (75.0) [33]
TEAEs related to study druga	6 (30.0) [10]	5 (26.3) [6]	10 (50.0) [16]
Serious TEAEs	1 (5.0) [1]b	1 (5.3) [1]c	2 (10.0) [2]
Serious TEAEs related to study druga	1 (5.0) [1]b	1 (5.3) [1]c	2 (10.0) [2]
TEAEs leading to early discontinuation	1 (5.0) [1]d	0	1 (5.0) [1]d
Deaths – all causes	0	0	0
AEs observed in ≥2 patients in any treatment period (preferred term)
Exertional dyspnea	0	3 (15.8) [3]	3 (15.0) [3]
Dyspnea	2 (10.0) [2]	0	2 (10.0) [2]
Dizziness	2 (10.0) [2]	0	2 (10.0) [2]
Headache	2 (10.0) [2]	1 (5.3) [1]	2 (10.0) [3]
Tremor	2 (10.0) [2]	1 (5.3) [1]	2 (10.0) [3]
Respiratory tract infection	2 (10.0) [2]	0	2 (10.0) [2]

Notes: Data are n (%) [events].

a Related: investigator’s assessment as possibly, probably, or definitely.

b Acute myocardial infarction.

c Acute coronary syndrome.

d Tremor.

Abbreviations: AE, adverse event; GFF, glycopyrrolate/formoterol fumarate; MDI, metered dose inhaler; TEAE, treatment-emergent adverse event.

Figure S1 Scatter plot comparison of change from baseline in siVaw (A) and siRaw (B) with change from baseline in sGaw at Day 15.

Abbreviations: GFF, glycopyrrolate/formoterol fumarate; MDI, metered dose inhaler; sGaw, specific airway conductance; siRaw, specific image-based airway resistance; siVaw, specific image-based airway volume.

Table S1 Prior COPD-related medications (safety/intent-to-treat population)

Medications	Total (N=20)
Any prior COPD medication	19 (95.0)
Tiotropium	10 (50.0)
Fluticasone	7 (35.0)
Fluticasone/salmeterol	7 (35.0)
Ipratropium/fenoterol	4 (20.0)
Salbutamol	4 (20.0)
Beclometasone	3 (15.0)
Glycopyrrolate/indacaterol	3 (15.0)
Beclometasone/formoterol fumarate	2 (10.0)
Umeclidinium/vilanterol	2 (10.0)
Budesonide	1 (5.0)
Budesonide/formoterol fumarate	1 (5.0)
Glycopyrrolate	1 (5.0)
Indacaterol	1 (5.0)
Roflumilast	1 (5.0)

Notes: Data are n (%). Overall, 19 patients received at least one COPD-related medication prior to study entry. Patients may have received more than one COPD-related medication.