Figures & data
Figure 1 Study design.
![Figure 1 Study design.](/cms/asset/51e0a29a-0650-4752-a9ce-8215424fdf83/dcop_a_189138_f0001_c.jpg)
Table 1 Baseline demographics and clinical characteristics (ITT population)
Figure 2 CONSORT flowchart.
![Figure 2 CONSORT flowchart.](/cms/asset/acefe112-a574-4548-b8b0-6ecee64f5d75/dcop_a_189138_f0002_b.jpg)
Figure 3 Change from baseline in 1-hour post-dose FEV1 at week 24, ITT population (co-primary endpoint).
Abbreviations: AB, aclidinium bromide; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium.
![Figure 3 Change from baseline in 1-hour post-dose FEV1 at week 24, ITT population (co-primary endpoint).](/cms/asset/54407700-0ac0-4c70-b3cc-27d5ab3a5d42/dcop_a_189138_f0003_c.jpg)
Figure 4 Change from baseline in trough FEV1 at week 24, ITT population (co-primary endpoint).
Abbreviations: AB, aclidinium bromide; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium.
![Figure 4 Change from baseline in trough FEV1 at week 24, ITT population (co-primary endpoint).](/cms/asset/5ce8c66d-c660-4ee0-82d3-73f3a894d562/dcop_a_189138_f0004_c.jpg)
Figure 5 Change from baseline in FEV1 over 3 hours post-dose and AUC0–3/3 h on (A) day 1 and (B) at week 24, ITT population.
Abbreviations: AB, aclidinium bromide; AUC, area under the curve; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium.
![Figure 5 Change from baseline in FEV1 over 3 hours post-dose and AUC0–3/3 h on (A) day 1 and (B) at week 24, ITT population.](/cms/asset/91ce6a90-b6d3-401e-8bfd-3827aaafa199/dcop_a_189138_f0005_c.jpg)
Figure 6 Severity of (A) NiSCI and (B) EMSCI over 24 weeks, ITT population.
Abbreviations: AB, aclidinium bromide; EMSCI, Early-Morning Symptoms of COPD Instrument; FF, formoterol fumarate; ITT, intent-to-treat; NiSCI, Nighttime Symptoms of COPD Instrument; TIO, tiotropium.
![Figure 6 Severity of (A) NiSCI and (B) EMSCI over 24 weeks, ITT population.](/cms/asset/84388a06-5ee5-4f17-a4f6-9fa402b6208b/dcop_a_189138_f0006_c.jpg)
Figure 7 Change from baseline in FEV1 over 24 hours post-dose (A) on day 1 and (B) at week 24, sub-study ITT population.
Notes: *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001 for AB/FF vs all other treatments. #P<0.05; ##P<0.01; ###P<0.001; ####P<0.0001 for AB/FF vs FF and TIO. ‡‡‡‡P<0.0001 for AB/FF vs AB and TIO. §P<0.05; §§P<0.01; §§§P<0.001 for AB/FF vs FF. Data are least squares means ± standard error.
Abbreviations: AB, aclidinium bromide; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.
![Figure 7 Change from baseline in FEV1 over 24 hours post-dose (A) on day 1 and (B) at week 24, sub-study ITT population.Notes: *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001 for AB/FF vs all other treatments. #P<0.05; ##P<0.01; ###P<0.001; ####P<0.0001 for AB/FF vs FF and TIO. ‡‡‡‡P<0.0001 for AB/FF vs AB and TIO. §P<0.05; §§P<0.01; §§§P<0.001 for AB/FF vs FF. Data are least squares means ± standard error.Abbreviations: AB, aclidinium bromide; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.](/cms/asset/13f83345-2694-4388-a75a-8992bf048c31/dcop_a_189138_f0007_c.jpg)
Figure 8 Change from baseline in normalized (A) AUC0–12/12 h, (B) AUC12–24/12 h, and (C) AUC0–24/24 h FEV1 at week 24, sub-study ITT population.
Abbreviations: AB, aclidinium bromide; AUC, area under the curve; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.
![Figure 8 Change from baseline in normalized (A) AUC0–12/12 h, (B) AUC12–24/12 h, and (C) AUC0–24/24 h FEV1 at week 24, sub-study ITT population.](/cms/asset/5eb406f8-d71e-4374-a0ca-68ccf4f52c5b/dcop_a_189138_f0008_c.jpg)
Figure 9 Severity of (A) NiSCI and (B) EMSCI over 24 weeks, sub-study ITT population.
Abbreviations: AB, aclidinium bromide; EMSCI, Early Morning Symptoms of COPD Instrument; FF, formoterol fumarate; ITT, intent-to-treat; NiSCI, Nighttime Symptoms of COPD Instrument; TIO, tiotropium bromide.
![Figure 9 Severity of (A) NiSCI and (B) EMSCI over 24 weeks, sub-study ITT population.](/cms/asset/1889ef2f-3484-4340-908b-0fd3b112a84c/dcop_a_189138_f0009_c.jpg)
Table 2 Incidence of treatment-emergent adverse events (safety population)
Independent Ethics Committees/Institutional Review Boards and Approval Numbers
Figure S1 Change from baseline in morning pre-dose (trough) FVC (A) at week 1, and (B) week 24, ITT population.
Notes: ***P<0.001; ****P<0.0001. Data are least squares means ± standard error.
Abbreviations: AB, aclidinium bromide; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.
![Figure S1 Change from baseline in morning pre-dose (trough) FVC (A) at week 1, and (B) week 24, ITT population.Notes: ***P<0.001; ****P<0.0001. Data are least squares means ± standard error.Abbreviations: AB, aclidinium bromide; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.](/cms/asset/358b427c-aba3-414d-a8ac-77174772731b/dcop_a_189138_sf0001_c.jpg)
Figure S2 Change from baseline in normalized AUC0–3/3 h FVC (A) on day 1 and (B) at week 24, ITT population.
Notes: **P<0.01; ****P<0.0001. Data are least squares means ± standard error.
Abbreviations: AB, aclidinium bromide; AUC, area under the curve; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.
![Figure S2 Change from baseline in normalized AUC0–3/3 h FVC (A) on day 1 and (B) at week 24, ITT population.Notes: **P<0.01; ****P<0.0001. Data are least squares means ± standard error.Abbreviations: AB, aclidinium bromide; AUC, area under the curve; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.](/cms/asset/9ba05560-423e-49a4-9875-19bfa446f397/dcop_a_189138_sf0002_c.jpg)
Figure S3 Change from baseline in normalized (A and B) AUC0–12/12 h, (C and D) AUC12–24/12 h, and (E and F) AUC0–24/24 h FVC at day 1 and week 24, sub-study ITT population. Notes: *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. Data are least squares means ± standard error.
Abbreviations: AB, aclidinium bromide; AUC, area under the curve; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.
![Figure S3 Change from baseline in normalized (A and B) AUC0–12/12 h, (C and D) AUC12–24/12 h, and (E and F) AUC0–24/24 h FVC at day 1 and week 24, sub-study ITT population. Notes: *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. Data are least squares means ± standard error.Abbreviations: AB, aclidinium bromide; AUC, area under the curve; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.](/cms/asset/19e446eb-8fef-498f-a0a8-8e862fc38973/dcop_a_189138_sf0003_c.jpg)
![Figure S3 Change from baseline in normalized (A and B) AUC0–12/12 h, (C and D) AUC12–24/12 h, and (E and F) AUC0–24/24 h FVC at day 1 and week 24, sub-study ITT population. Notes: *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001. Data are least squares means ± standard error.Abbreviations: AB, aclidinium bromide; AUC, area under the curve; FF, formoterol fumarate; ITT, intent-to-treat; TIO, tiotropium bromide.](/cms/asset/97915a4c-7542-46a6-a5e5-78a73f338b5e/dcop_a_189138_sf0003b_c.jpg)
Table S1 Baseline demographics and clinical characteristics (sub-study ITT population)
Data availability
Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data sharing policy described at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
The protocol and the statistical analysis plan can be found at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/View?id=22775.