Pneumologie 2015; 69 - P232
DOI: 10.1055/s-0035-1544687

Results of three Phase II trials with the long-acting β2-adrenergic agonist (LABA) abediterol in patients with persistent asthma

J Beier 1, D Singh 2, R Fuhr 3, S Ruiz 4, B Seoane 5, E Massana 4, E Jimenez 6, H Pujol 4, C Astbury 7, G de Miquel 8
  • 1Insaf Respiratory Research Institute Wiesbaden
  • 2Medicines Evaluation Unit Ltd, University of Manchester
  • 3Early Phase Clinical Unit; PAREXEL Berlin
  • 4Global Clinical Development, Almirall S.A. Barcelona
  • 5Biometry, Almirall S.A. Barcelona
  • 6Pharmacokinetics and Drug Metabolism, Almirall S.A. Barcelona
  • 7Early Clinical Development, Almirall S.A. Barcelona
  • 8Global Medical Affairs, Almirall S.A. Barcelona

Introduction: Efficacy and safety of abediterol (LAS100977), a novel LABA in development as a fixed dose combination with an inhaled corticosteroid for the treatment of asthma and COPD, were investigated in 3 Phase II trials in patients with persistent, stable asthma.

Methods: Randomized, double-blind, placebo-controlled, crossover designs were used. Single doses (dose range: 0.313 to 25 µg) of abediterol were administered in the morning via Cyclohaler® (Study 1 and 2) or Genuair® (Study 3). In studies 1 and 3, active comparators (salmeterol and salbutamol, respectively) were used. Change from baseline in FEV1 was assessed and treatment emergent adverse events (TEAEs) were recorded.

Results: Abediterol, in all doses, produced rapid (≤ 15 minutes post-dose), sustained, clinically significant bronchodilation and a significant higher trough FEV1 versus placebo (table). TEAEs were consistent with the drug class and most were mild to moderate in intensity.

Tab. 1: Change from baseline in trough FEV1 (L) across a range of abediterol doses

*p < 0.001, **p < 0.0001 vs placebo; ††p < 0.0001 vs abediterol (all doses);

aper protocol population; bintent-to-treat population

Data are LS mean differences from placebo (SE). Trough FEV1 was the mean of the 23 and 24 hour FEV1 values.

BID, twice daily; FEV1, forced expiratory volume in 1 second; LS, least squares; N, randomized patients; QD, once daily; SE, standard error

Through FEV 1

Study 1 a

N= 25

Study 2 a

N= 28

Study 3 b

N= 62

Abediterol

0.313 µg QD

-

-

0.219**

(0.042)

Abediterol

0.625 µg QD

-

0.281**

(0.048)

0.259**

(0.042)

Abediterol

1.25 µg QD

-

0.296*

(0.067)

0.332**

(0.042)

Abediterol

2.5 µg QD

-

-

0.400**

(0.042)

Abediterol

5 µg QD

0.612**

(0.056)

0.516**

(0.049)

-

Abediterol

10 µg QD

0.636**

(0.055)

-

-

Abediterol

25 µg QD

0.665**

(0.055)

-

-

Salmeterol

50 µg BID

0.309**††

(0.055)

-

-

Salbutamol

400 µg QD

-

-

-0.022††

(0.042)

Conclusions: Abediterol effectively improved bronchodilation in patients with asthma compared with placebo and was safe and well tolerated.