A 52-week treatment, multi-center, randomized, doubleblind, double dummy, parallel-group, active controlled study to compare the effect of QVA149 (indacaterol maleate / glycopyrronium bromide) with salmeterol/fluticasone on the rate of exacerbations in subjects with moderate to very severe COPD (CQVA149A2318)

Morbidity and mortality due to COPD are increasing. COPD results in a
progressive and irreversible decline of the pulmonary function and
exacerbations (more symptoms, decreased pulmonary function, decreased quality
of life and increased risk for complications), that increase in frequency when
the severity of the disease increases.
Anticholinergics and long acting beta2-mimetics belong to the cornerstones of
COPD treatment.
QVA149 is a combination of a long acting beta2-agonist (indacaterol) and the
anticholinergic drug glycopyrronium bromide.
In this study the effects of QVA149 will be compared to those of Seretide, that
is often prescribed in daily practice. Seretide is a combination of the long
acting beta2 agonist salmeterol and the inhaled corticosteroid fluticasone. It
is administered twice daily.

Primary objective: To demonstrate that QVA149 (110/50 *g o.d.) is at least
non-inferior to salmeterol/fluticasone (50/500 *g b.i.d.) in terms of rate of
COPD exacerbations.
Secondary objectives: Superiority in terms of exacerbation rate. Time to first
exacerbation, FEV1, St George questionaire, rescue medication, COPD symptoms,
safety and tolerability.

Randomized double blind, parallel group phase III study. Screening, s.n.
adjustment current COPD medication, followed by 4 week run-in period (with
titotropium). Thereafter randomisation (1:1) to treatment with:
* QVA149 110/50 mcg o.d.
* Serevent 50/500 mcg twice daily
via dry powder inhaler.
Rescue medication.
Total treatment duration approx. 52 weeks.
Approx. 3000 patients.

Treatment with QVA149 or Seretide.

Risk: Adverse effects of study medication. Changes in current COPD medication.
Burden: 14 visits in 1 year. Every 2 weeks telephone call. Telephone call 4
weeks after end of treatment.
Daily electronic diary (signs, symptoms, rescue medication). Physical exam 5x,
blood tests (safety) 4x (approx. 10 ml blood/visit, total amount 40 ml),
pregnancy test 2x, 1x pulmonary function test with reversibility, 7 visits with
pulmonary function tests, thereof 6 with 4 tests per visit. 5x ECG (on 3
occasions 2 ECG's). Questionnaires 6x.
Extra tests (not in all centres): 3x collection 24 h urine for cortisol. During
6 visits 4 additional pulmonary function tests (in the 12 h post medication).
Completion of extra diary.