A Study to Assess the Long-term Safety of QVA149 (ENLIGHTEN)

A Multicener, Randomised, Double-blind, Placebo-controlled Study, to Assess the Long Term Safety of 52 Weeks Treatment With QVA149 (110 ug Indacaterol/50ug Glycopyrrolate) in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

The study is designed to provide long-term safety data for QVA149 in patients with moderate to severe chronic obstructive pulmonary disease (COPD).

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: QVA149; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 339
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1P 1J6
    • Novartis Investigative Site
  • Ontario
    • Toronto, Ontario, Canada, M3H 5S4
      • Novartis Investigative Site
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
      • Novartis Investigative Site
    • Québec, Quebec, Canada, G1G 3Z4
      • Novartis Investigative Site
• France
  • Beuvry, France, 62660
    • Novartis Investigative Site
  • Ferolles-Attily, France, 77150
    • Novartis Investigative Site
  • Montpellier, France, 34059
    • Novartis Investigative Site
  • Nantes, France, 44000
    • Novartis Investigative Site
  • Pessac, France, 33604
    • Novartis Investigative Site
• Hungary
  • Aszod, Hungary, 2170
    • Novartis Investigative Site
  • Baja, Hungary, 6500
    • Novartis Investigative Site
  • Erd, Hungary, 2030
    • Novartis Investigative Site
  • Godollo, Hungary, 2100
    • Novartis Investigative Site
  • Makó, Hungary, 6900
    • Novartis Investigative Site
• India
  • Chennai - Tamil Nadu, India, 600 087
    • Novartis Investigative Site
  • Mangalore, India
    • Novartis Investigative Site
  • Delhi
    • New Delhi, Delhi, India, 110029
      • Novartis Investigative Site
  • Karnataka
    • Banglaore, Karnataka, India, 560027
      • Novartis Investigative Site
    • Mysore, Karnataka, India, 570004
      • Novartis Investigative Site
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452001
      • Novartis Investigative Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400007
      • Novartis Investigative Site
  • New Delhi
    • Dehli, New Delhi, India, 110063
      • Novartis Investigative Site
  • Tamil Nadu
    • Coimbatore, Tamil Nadu, India, 641044
      • Novartis Investigative Site
• Korea, Republic of
  • Busan, Korea, Republic of, 602-739
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 140-743
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 158-710
    • Novartis Investigative Site
  • Gyeonggi-do
    • Koyang-si, Gyeonggi-do, Korea, Republic of, 410-773
      • Novartis Investigative Site
• Latvia
  • Daugavpils, Latvia, LV-5401
    • Novartis Investigative Site
  • Jekabpils, Latvia, LV-5201
    • Novartis Investigative Site
  • Riga, Latvia, 1002
    • Novartis Investigative Site
  • LV
    • Riga, LV, Latvia, LV-1038
      • Novartis Investigative Site
• Lithuania
  • Alytus, Lithuania, LT-62114
    • Novartis Investigative Site
  • Kaunas, Lithuania, 44320
    • Novartis Investigative Site
  • Klaipeda, Lithuania, 92288
    • Novartis Investigative Site
  • Klaipeda, Lithuania, LT-92231
    • Novartis Investigative Site
  • Vilnius, Lithuania, LT-08661
    • Novartis Investigative Site
  • Vilnius, Lithuania, 06001
    • Novartis Investigative Site
• Romania
  • District 1
    • Bucharest, District 1, Romania, 011422
      • Novartis Investigative Site
    • Bucharest, District 1, Romania, 10457
      • Novartis Investigative Site
  • District 3
    • Bucharest, District 3, Romania, 030303
      • Novartis Investigative Site
  • Jud. Brasov
    • Brasov, Jud. Brasov, Romania, 500118
      • Novartis Investigative Site
  • Jud. Iasi
    • Iasi, Jud. Iasi, Romania, 700115
      • Novartis Investigative Site
• South Africa
  • Pretoria, South Africa, 0184
    • Novartis Investigative Site
  • Pretoria, South Africa
    • Novartis Investigative Site
• United Kingdom
  • Bath, United Kingdom, BA1 2SR
    • Novartis Investigative Site
  • Bath, United Kingdom, BA2 3HT
    • Novartis Investigative Site
  • Cambridge, United Kingdom, CB7 5JD
    • Novartis Investigative Site
  • Chesterfield, United Kingdom, S40 4TF
    • Novartis Investigative Site
  • Glasgow, United Kingdom, G69 7AD
    • Novartis Investigative Site
  • Irvine, United Kingdom, KA12 0AY
    • Novartis Investigative Site
  • Lancashire, United Kingdom, FY3 7EN
    • Novartis Investigative Site
  • Watford, United Kingdom, WD25 0EA
    • Novartis Investigative Site
  • Wellingborough, United Kingdom, NN8 4RW
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female adults aged ≥40 yrs
• Smoking history of at least 10 pack years
• Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008)
• Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) <70%

Exclusion Criteria:

• Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1
• Patients with concomitant pulmonary disease
• Patients with a history of asthma
• Any patient with lung cancer or a history of lung cancer
• Patients with a history of certain cardiovascular co-morbid conditions
• Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
• Patients in the active phase of a supervised pulmonary rehabilitation program
• Patients contraindicated for inhaled anticholinergic agents and β2 agonists
• Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QVA149; 110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)	Drug: QVA149; capsules for inhalation, delivered by an SDDPI
Placebo Comparator: Placebo; Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI	Drug: Placebo; capsules for inhalation, delivered by an SDDPI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events, Serious Adverse Events or Death	Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.	52 weeks + Follow-up (Up to Day 394)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pre-dose FEV1	Pre-dose FEV1 is defined as the average of the FEV1 15 minutes pre-dose and FEV1 45 minutes pre-dose. A mixed model was used with treatment as a fixed effect, average of 15 min and 45 min pre-dose FEV1 at visit 3 as the baseline measurement, and FEV1 prior to inhalation and FEV1 60 min post inhalation of two short acting bronchodialators as covariates. The model also included smoking status at baseline, history of ICS use and country as fixed effects with center nested within country as a random effect.	52 weeks
Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period	Clinically notable hematology values were: hemoglobin - male <115g/L, female <95 g/L; hematocrit - male <0.37v/v, female <0.32v/v; white cell count - <2.8 10E9/L or >16.0 10E9/L; platelets - <75 10E9/L or >700 10E9/L	52 weeks
Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period	Clinically notable biochemistry values were: sodium <125mmol/L or >160mmol/L; potassium <3.0mmol/L or >6.0mmol/L; BUN >9.99mmol/L; creatinine >176.8µmol/L; total protein (serum) <40g/L or >95g/L; albumin <25g/L; bilirubin (total) >34.2µmol/L; SGPT >3 x ULN; SGOT > 3 x ULN; gamma glutamyltransferase >3 x ULN; alkaline phosphatase (serum) >3 x ULN; glucose <2.78mmol/L or >9.99mmol/L	52 weeks
Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period	Clinically notable vital sign values were: pulse rate - low, <40 bpm or <=50 bpm and decrease from baseline >=15bpm; pulse rate high, >130 bpm or >=120bpm and increase from baseline >=15 bpm. Systolic blood pressure - low, <75 mmHg or <=90 mmHg and decrease from baseline >=20 mmHg; high, >200 mmHg or >=180 mmHg and increase from baseline >=20 mmHg. Diastolic blood pressure - low, <40 mmHg or <=50 mmHg and decrease from baseline >=15 mmHg; high, >115 mmHg or >=105 mmHg and increase from baseline >=15 mmHg.	52 weeks
Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period	Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).	52 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Buhl R, Gessner C, Schuermann W, Foerster K, Sieder C, Hiltl S, Korn S. Efficacy and safety of once-daily QVA149 compared with the free combination of once-daily tiotropium plus twice-daily formoterol in patients with moderate-to-severe COPD (QUANTIFY): a randomised, non-inferiority study. Thorax. 2015 Apr;70(4):311-9. doi: 10.1136/thoraxjnl-2014-206345. Epub 2015 Feb 12.
• Dahl R, Chapman KR, Rudolf M, Mehta R, Kho P, Alagappan VK, Chen H, Banerji D. Safety and efficacy of dual bronchodilation with QVA149 in COPD patients: the ENLIGHTEN study. Respir Med. 2013 Oct;107(10):1558-67. doi: 10.1016/j.rmed.2013.05.016. Epub 2013 Jul 16.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: May 5, 2010
• First Submitted That Met QC Criteria: May 10, 2010
• First Posted (Estimate): May 11, 2010

Study Record Updates

• Last Update Posted (Estimate): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 28, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: COPD; QVA149; combination bronchodilator
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CQVA149A2307; 2009-013235-38 (EudraCT Number)