copd drug QVA 149 trials

1. ILLUMINATE trial Sept. 2013
&
SPARK trial, May 2013
Dr. Ankur Gupta

2. Efficacy and safety of once-daily QVA149
compared with twice-daily salmeterol–
fluticasone in patients with chronic
obstructive pulmonary disease (ILLUMINATE):
a randomised, double-blind, parallel group
study
Claus F Vogelmeier, Eric D Bateman, John Pallante, Vijay K T Alagappan, Peter D’Andrea,
Hungta Chen, Donald Banerji
Lancet Respir Med 2013; 1: 51–60

3. STUDY QUESTION
• In a low-risk but symptomatic population of
COPD patients, whether intensive
bronchodilator maintenance treatment alone
(with two long acting bronchodilators) is safe
and offers benefits compared with the
common practice of using a combined LABA
and ICS ?

4. STUDY DESIGN
93 centres in ten countries. March 2011 to March 2012

5. TRIAL PROFILE

6. BASELINE CHARACTERISTICS

7. EFFICACY ENDPOINTS
Primary -
Superiority of QVA149 (indacaterol 110 μg and
glycopyrronium 50 μg in breezehaler device)
once a day compared with Salmeterol–
fluticasone (SFC 50/500 μg in accuhaler
device) twice a day for the standardized area
under the curve from 0 to 12 h post dose for
FEV₁ (FEV₁ AUC 0–12h) after 26 weeks of
treatment.

8. EFFICACY ENDPOINTS
Secondary –
• Other spirometric endpoints
• Transition dyspnoea index focal scores
• SGRQ-C total scores
• Rescue medication use
• Daily patient-reported clinical symptoms,
recorded morning and evening with an
electronic diary

9. SAFETY ENDPOINTS
• Recording of treatment related adverse events

10. RESULTS - PRIMARY END POINT

11. RESULTS - PRIMARY AND SECONDARY
ENDPOINTS

12. RESULTS – QVA149 v/s SFC
Rapid oncet bronchodilation and significant
improvement in FEV₁ at day 1, week 12 and
26.
Significant improvement in FVC at week 12 and
26.
Significant increase in transition dyspnea index
score at week 26.
Significant decrease in rescue medicine use.

13. RESULTS – QVA149 v/s SFC
SGRQ-C total scores were not different between
treatment groups
Incidence of serious adverse events was similar
between treatment groups. Further evidence
on the long-term safety of QVA149 has been
investigated in the 52-week ENLIGHTEN trial

15. Analysis of chronic obstructive pulmonary
disease exacerbations with the dual
bronchodilator QVA149 compared with
glycopyrronium and tiotropium (SPARK): a
randomised, double-blind, parallel-group
study
Jadwiga A Wedzicha, Marc Decramer, Joachim H Ficker, Dennis E Niewoehner, Thomas
Sandström, Angel Fowler Taylor, Peter D’Andrea, Christie Arrasate, Hungta Chen, Donald
Banerji
Lancet Respir Med 2013; 1: 199–209

16. AIM OF STUDY
• To evaluate the effect of once-daily QVA149
(110/50 μg) on exacerbations of COPD, in
patients with severe or very severe airflow
limitation and who were at high risk of future
adverse outcomes (at least one exacerbation
in the past year).
• To compare the effect of QVA149 with the
once-daily LAMAs Glycopyrronium (50 μg)and
Tiotropium (18 μg).

17. STUDY DESIGN
• Multicentre study (362 centres across 27
countries), consisting of a pre-randomisation
period and a double blind, parallel-group
treatment period (64 weeks).
• Study period – April 2010 to July 2012

19. BASELINE CHARACTERISTICS

20. EFFICACY ENDPOINTS
Primary
• To demonstrate superiority of QVA149
compared with glycopyrronium for the rate of
moderate or severe COPD exacerbations
during the treatment period.

21. EFFICACY ENDPOINTS
Secondary
• To demonstrate superiority of QVA149 compared
with tiotropium with respect to COPD
exacerbations during the treatment period.
• To demonstrate the effect of QVA149 versus
glycopyrronium and tiotropium on
1)Bronchodilator effect (predose or trough
FEV₁)
2)Health status (SGRQ total score)
3)Use of rescue salbutamol during the
treatment period.

22. EXACERBATIONS
• COPD exacerbation - presence of two major
symptoms (dyspnoea, sputum volume, sputum
purulence) for at least 2 consecutive days
or
• A worsening of one major symptom together
with an increase in any one minor symptom (sore
throat, colds, fever without other cause, cough,
wheeze) for at least 2 consecutive days.

23. • Mild COPD exacerbation -Worsening of the
above symptoms; self-managed by the patient
and did not require treatment with systemic
corticosteroids or antibiotics.
• Moderate COPD exacerbation - Requirement
for treatment with systemic corticosteroids or
antibiotics or both.
• Severe COPD exacerbation - Hospital
admission, including an emergency room visit
of longer than 24 h.

26. Results – primary endpoint
(execerbation)
mild Moderate to
severe
severe All
execerbation
QVA149
compared to
glycopyrronium
15 % reduction 12 % reduction No significant
reduction
15 % reduction
QVA149
compared to
tiotropium
16 % reduction 10 % reduction No significant
reduction
14 % reduction

27. RESULTS – SECONDARY ENDPOINTS
(Trough FEV1 )
Trough FEV₁ was significantly higher with
QVA149 at all assessments compared with
glycopyrronium (differences 70–80 mL;
p<0.0001) and tiotropium (differences 60–80
mL; p<0.0001).

28. RESULTS – SECONDARY ENDPOINTS
(SGRQ)
SGRQ total score were significantly higher
with QVA149 than with glycopyrronium or
tiotropium up to week 52.

29. RESULTS – SECONDARY ENDPOINTS
(rescue medicine usage)
• use of rescue salbutamol decreased by 2.3
puffs per day (SE 0.13) with QVA149 (QVA149−
glycopyrronium least squares mean treatment
difference −0.81, p<0.0001;
QVA149−tiotropium least squares mean
treatment difference −0.76, p<0.0001), and
decreased by 1.5 puffs per day (SE 1.3) with
glycopyrronium and with tiotropium.

30. • No untoward safety findings were apparent
with the dual bronchodilator approach
compared with the single LAMA treatments
investigated in this study; all treatments were
well tolerated and had acceptable profiles of
cardio-cerebrovascular safety. The overall
safety profile of QVA149 was similar to the
individual LAMAs.

31. SUMMARY
ILLUMINATE TRIAL
• QVA149 compared with
salmeterol–fluticasone
(SFC)
• Efficacy, safety, and
tolerability
• Study group – moderate to
severe COPD.
• 26 weeks
SPARK TRIAL
• QVA149 compared with
glycopyrronium and
tiotropium
• Exacerbations
• Study group - severe and
very severe COPD.
• 64 weeks

32. SUMMARY
ILLUMINATE TRIAL
• RESULT - Once-daily
QVA149 provides
significant, sustained, and
clinically meaningful
improvements in lung
function versus twice-daily
SFC, with significant
symptomatic benefit.
SPARK TRIAL
• RESULTS - QVA149 was
superior in preventing
moderate to severe COPD
exacerbations compared
with the single LAMA
(glyco/tio), with
concomitant improvements
in lung function and health
status

33. THANK YOU