Pneumologie 2016; 70 - P364
DOI: 10.1055/s-0036-1572048

Efficacy of aclidinium/formoterol fixed-dose combination versus salmeterol/fluticasone in COPD

C Vogelmeier 1, P Paggiaro 2, J Dorca 3, P Sliwinski 4, M Mallet 5, AM Kirsten 6, B Seoane 7, RM Segarra 7, A Leselbaum 8, EG Gil 7
  • 1Innere Medizin, Sp Pneumologie, Universitätsklinikum Gießen u. Marburg, Standort Marburg
  • 2Respiratory Pathophysiology, University Hospital of Pisa
  • 3Hospital Universitari de Bellvitge and Institut D'investigació Biomèdica de Bellvitge (Idibell), University of Barcelona
  • 4Institute of Tuberculosis and Lung Diseases
  • 5Université Laval
  • 6Pneumologisches Forschungsinstitutan der Lungenclinic Grosshansdorf GmbH
  • 7Astrazeneca Plc
  • 8Former Employee of Almirall S.A.

Background: Aclidinium bromide/formoterol fumarate fixed-dose combination (FDC) twice daily (BID) is licensed in Europe for COPD treatment.

Aim: To evaluate the efficacy of aclidinium/formoterol vs. salmeterol/fluticasone propionate FDC (SAL/FLU) in patients with COPD.

Methods: A randomised, double-blind, Phase IIIb, 24-week study in patients with COPD Assessment Test (CAT) score ≥10 compared aclidinium/formoterol 400/12 µg BID via Genuair® with SAL/FLU 50/500 µg BID via Accuhaler® (NCT01908140). Endpoints were peak FEV1 (primary), Transition Dyspnoea Index (TDI; secondary), CAT, device preference and exacerbations. Non-inferiority of aclidinium/formoterol vs. SAL/FLU was tested for peak FEV1 and TDI. Superiority in peak FEV1 was also analysed. Adverse events (AEs) were monitored throughout.

Results: 933 patients were randomised: mean age 63.4 years; 65.1% male; mean post bronchodilator FEV1 1.48 L (53.2% predicted); mean CAT score 18.5. 788 patients (84.5%) completed the study.

Aclidinium/formoterol achieved greater peak FEV1 vs. SAL/FLU from Day 1 to Week 24 (p < 0.0001; Table). Improvements in TDI, CAT and exacerbations were similar in both groups (Table). More patients preferred Genuair (51.9%) than Accuhaler (18.5%, p < 0.0001).

The incidence of AEs, and AEs leading to study discontinuation was similar across groups. The most common AEs were COPD exacerbations (17.5%), headache (6.4%) and nasopharyngitis (5.8%).

Conclusion: Superiority in peak FEV1 and non-inferiority in TDI were demonstrated for aclidinium/formoterol FDC vs. SAL/FLU in patients with stable COPD. Improvements in quality of life and exacerbations were similar in both groups. More patients preferred Genuair to Accuhaler. Both treatments were well tolerated.

Tab. 1: Efficacy of aclidinium/formoterol FDC vs. salmeterol/fluticasone FDC

Aclidinium/formoterol

400/12 µg BID

n = 468

Salmeterol/fluticasone

50/500 µg BID

n = 463

Peak FEVi at baseline, L,

mean (95% Cl)a

1.39

(1.34, 1.44)

1.38

(1.33, 1.43)

PeakFEVi at Week 24, L,

mean (95% Cl)b

1.66

(1.63, 1.68)"'

1.56

(1.54, 1.58)

TDI focal score at Week 24,

units, mean (95% Cl)b,c

1.88

(1.54, 2.21)

1.88

(1.54, 2.22)

CAT total score at Week 24,

units, mean (95% Cl)b

15.81

(15.23, 16.40)

16.11

(15.53, 16.70)

Patients with ≥1 HCRU-

defined exacerbation during

study, %

15.8

16.6

Patients with ≥1 EXACT-

identified exacerbation

during study, %

37.8

39.5

Efficacy data were analysed in the intent-to-treat population with the exception of TDI focal score, which was analysed in the per-protocol population (non-inferiority analyses)

66 (14.1%) patients in the aclidinium/formoterol group and 79 (17.0%) in the salmeterol/fluticasone group did not complete the study

Two patients randomised to aclidinium/formoterol 400/12 µg BID received salmeterol/fluticasone 50/500 µg BID; one patient randomised to salmeterol/fluticasone 50/500 µg BID received aclidinium/formoterol 400/12 µg BID. Efficacy data for these patients were analysed according to randomisation, safety data were analysed according to received treatment.

aAbsolute value

bData reported as least squares means

cPer-protocol population: aclidinium/formoterol 400/12 µg BID n = 423; salmeterol/fluticasone 50/500 µg BID n = 414

***p < 0.0001 vs. salmeterol/fluticasone

95% CI, 95% confidence interval; BID, twice daily; CAT, COPD Assessment Test; EXACT, EXAcerbations of Chronic pulmonary disease Tool; FEV1, forced expiratory volume in 1 second; HCRU, healthcare resource utilisation; TDI, Transition Dyspnoea Index

Funding

This study was funded by Almirall S.A., Barcelona, Spain. Medical writing support, funded by AstraZeneca PLC, Barcelona, Spain, was provided by Richard Knight of Complete Medical Communications.