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DOI: 10.1055/s-0035-1544790
Safety of aclidinium bromide/formoterol fumarate fixed-dose combination in COPD: pooled analyses of three Phase III studies
Background: Two 24-week Phase III studies (ACLIFORM and AUGMENT) and a 28-week AUGMENT extension study assessed the efficacy and safety of two twice-daily aclidinium/formoterol fixed-dose combinations (FDC) in patients with moderate-to-severe COPD.
Aim: To assess adverse events (AEs) in a pooled analysis of the three Phase III studies.
Methods: The studies were randomized, double-blind, placebo- and active-controlled. Patients received placebo, formoterol 12 µg, aclidinium 400 µg, FDC 400/6 µg or FDC 400/12 µg twice daily. Patients who continued into the extension study from AUGMENT remained on the same treatment. AEs were monitored throughout.
Results: In total, 3398 patients comprised the pooled placebo-controlled safety population (mean age 64 years; 61% male; 49% current smoker; 59% moderate COPD). Overall, the frequency and severity of AEs and the number of deaths was comparable across groups (Table). In addition, the only AEs reported by ≥3% of patients and with a frequency ≥0.5% higher in either FDC group versus placebo were nasopharyngitis, headache, urinary tract infection, sinusitis and nausea. Discontinuations due to AEs were most common with placebo. The only AE leading to discontinuation in ≥1% of patients in any group was COPD exacerbation and this was more frequent with placebo (2.3%) than either FDC (1.0 – 1.9%).
Conclusions: Overall, the safety profile of aclidinium/formoterol FDC twice daily was comparable with placebo and with the individual monotherapies.
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All treatments were administered via Genuair®/Pressair® (registered trademarks of Almirall S.A., Barcelona, Spain, for use within the United States as Pressair® and Genuair® within all other licensed territories) aAEs occurring after the first dose of treatment and up to 30 days following the last dose. BID, twice daily; FDC, aclidinium/formoterol fixed-dose combination |
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|
Formoterol |
Aclidinium |
FDC |
FDC |
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|
Placebo |
12 µg |
400 µg |
400/6 µg |
400/12 µg |
|
|
BID |
BID |
BID |
BID |
BID |
|
|
n (%) |
n = 526 |
n = 716 |
n = 722 |
n = 714 |
n = 720 |
|
≥1AE |
327 (62.2) |
470 (65.6) |
452 (62.6) |
442 (61.9) |
449 (62.4) |
|
Any severe AE |
57 (10.8) |
68 (9.5) |
73 (10.1) |
73 (10.2) |
78 (10.8) |
|
AEs in ≥ 5% of patients in any treatment group |
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|
COPD |
109 (20.7) |
154 (21.5) |
142 (19.7) |
129 (18.1) |
123 (17.1) |
|
Nasopharyngitis |
33 (6.3) |
58 (8.1) |
50 (6.9) |
53 (7.4) |
57 (7.9) |
|
Headache |
29 (5.5) |
56 (7.8) |
50 (6.9) |
42 (5.9) |
49 (6.8) |
|
Any serious AE |
39 (7.4) |
49 (6.8) |
53 (7.3) |
58 (8.1) |
58 (8.1) |
|
Serious AEs in ≥ 1% of patients in any treatment group |
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|
COPD exacerbation |
14 (2.7) |
12 (1.7) |
20 (2.8) |
15 (2.1) |
11 (1.5) |
|
Pneumonia |
4 (0.8) |
3 (0.4) |
3 (0.4) |
8 (1.1) |
5 (0.7) |
|
AnyAE leading to treatment discontinuation |
44 (8.4) |
41 (5.7) |
49 (6.8) |
44 (6.2) |
52 (7.2) |
|
Deaths |
2 (0.4) |
2 (0.3) |
4 (0.6) |
3 (0.4) |
4 (0.6) |
Funding: This study was supported by Almirall S.A., Barcelona, Spain and Forest Laboratories LLC, a subsidiary of Actavis plc, New York, NY, USA