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International Journal of Chronic Obstructive Pulmonary Disease Volume 14, 2019 - Issue
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Original Research

AMPLIFY: a randomized, Phase III study evaluating the efficacy and safety of aclidinium/formoterol vs monocomponents and tiotropium in patients with moderate-to-very severe symptomatic COPD

Sanjay Sethi1 Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA, [email protected]Correspondence[email protected]
,
Edward Kerwin2 Clinical Research Institute, Medford, OR, USA
,
Henrik Watz3 Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany
,
Gary T Ferguson4 Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA
,
Robert M Mroz5 Centrum Medycyny Oddechowej, Białystok, Poland;6 Medical University of Białystok, Białystok, Poland
,
Rosa Segarra7 AstraZeneca, Barcelona, Spain
,
Eduard Molins7 AstraZeneca, Barcelona, Spain
,
Diana Jarreta7 AstraZeneca, Barcelona, Spain
&
Esther Garcia Gil7 AstraZeneca, Barcelona, Spain
 show all
Pages 667-682 | Published online: 22 Mar 2019

Figures & data

Figure 1 Study design.

Abbreviations: AB, aclidinium bromide; BID, twice daily; FF, formoterol fumarate; QD, once daily; TIO, tiotropium.
Figure 1 Study design.

Table 1 Baseline demographics and clinical characteristics (ITT population)

Figure 2 CONSORT flowchart.

Abbreviations: AB, aclidinium bromide; FF, formoterol fumarate; TIO, tiotropium.
Figure 2 CONSORT flowchart.

Figure 3 Change from baseline in 1-hour post-dose FEV1 at week 24, ITT population (co-primary endpoint).

Notes: ****P<0.0001. Data are least squares means ± standard error.
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).

Figure 4 Change from baseline in trough FEV1 at week 24, ITT population (co-primary endpoint).

Notes: ***P<0.001. Data are least squares means ± standard error.
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).

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.

Notes: *P<0.05; **P<0.01; ***P<0.001; ****P<0.0001 vs all other treatments. #P<0.01 vs FF. ‡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.
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.

Figure 6 Severity of (A) NiSCI and (B) EMSCI over 24 weeks, ITT population.

Notes: *P<0.05. Data are least squares means ± standard error.
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.

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.

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.

Notes: *P<0.05; ***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 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.

Figure 9 Severity of (A) NiSCI and (B) EMSCI over 24 weeks, sub-study ITT population.

Notes: *P<0.05. Data are least squares means ± standard error.
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.

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.

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.

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.
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.

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.

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