ILLUMINATE trial Sept. 2013&

SPARK trial, May 2013

Dr. Ankur Gupta

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

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 ?

STUDY DESIGN

93 centres in ten countries. March 2011 to March 2012

TRIAL PROFILE

BASELINE CHARACTERISTICS

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 accuhalerdevice) 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.

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

SAFETY ENDPOINTS

• Recording of treatment related adverse events

RESULTS - PRIMARY END POINT

RESULTS - PRIMARY AND SECONDARY ENDPOINTS

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.

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

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

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).

STUDY DESIGN

• Multicentre study (362 centres across 27 countries), consisting of a pre-randomisationperiod and a double blind, parallel-group treatment period (64 weeks).

• Study period – April 2010 to July 2012

BASELINE CHARACTERISTICS

EFFICACY ENDPOINTS

Primary

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

EFFICACY ENDPOINTSSecondary

• 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.

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.

• 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.

Results – primary endpoint (execerbation)

mild Moderate to severe

severe All execerbation

QVA149compared to glycopyrronium

15 % reduction 12 % reduction No significant reduction

15 % reduction

QVA149 compared to tiotropium

16 % reduction 10 % reduction No significant reduction

14 % reduction

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).

RESULTS – SECONDARY ENDPOINTS (SGRQ)

SGRQ total score were significantly higher with QVA149 than with glycopyrronium or tiotropium up to week 52.

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.

• 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.

SUMMARYILLUMINATE 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

SUMMARYILLUMINATE 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

THANK YOU