A Study to Assess the Long-term Safety of QVA149 (ENLIGHTEN)
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
QVA149
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring QVA149, COPD, combination bronchodilator
Eligibility Criteria
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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
QVA149
Placebo
Arm Description
110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)
Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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
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
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.
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01120717
Brief Title
A Study to Assess the Long-term Safety of QVA149
Acronym
ENLIGHTEN
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study is designed to provide long-term safety data for QVA149 in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
QVA149, COPD, combination bronchodilator
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
339 (Actual)
8. Arms, Groups, and Interventions
Arm Title
QVA149
Arm Type
Experimental
Arm Description
110µg/50µg capsule for oral inhalation, once daily, delivered by a single dose dry powder inhaler (SDDPI)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo to match QVA149, capsules for inhalation once daily, delivered by an SDDPI
Intervention Type
Drug
Intervention Name(s)
QVA149
Intervention Description
capsules for inhalation, delivered by an SDDPI
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
capsules for inhalation, delivered by an SDDPI
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events, Serious Adverse Events or Death
Description
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.
Time Frame
52 weeks + Follow-up (Up to Day 394)
Secondary Outcome Measure Information:
Title
Pre-dose FEV1
Description
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.
Time Frame
52 weeks
Title
Number of Patients With Newly Occurring or Worsening Clinically Notable Hematology Values at Any Timepoint Over the Whole Treatment Period
Description
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
Time Frame
52 weeks
Title
Number of Patients With Newly Occurring or Worsening Clinically Notable Biochemistry Values at Any Timepoint Over the Whole Treatment Period
Description
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
Time Frame
52 weeks
Title
Number of Patients With Newly Occurring or Worsening Clinically Notable Vital Signs Values at Any Timepoint Over the Whole Treatment Period
Description
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.
Time Frame
52 weeks
Title
Number of Patients With Notable Change From Baseline in Fridericia's QTc Values at Any Timepoint Over the Whole Treatment Period
Description
Clinically notable change from baseline was and increase from baseline of 30 or greater milliseconds (ms).
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M3H 5S4
Country
Canada
Facility Name
Novartis Investigative Site
City
Mirabel
State/Province
Quebec
ZIP/Postal Code
J7J 2K8
Country
Canada
Facility Name
Novartis Investigative Site
City
Québec
State/Province
Quebec
ZIP/Postal Code
G1G 3Z4
Country
Canada
Facility Name
Novartis Investigative Site
City
Quebec
ZIP/Postal Code
G1P 1J6
Country
Canada
Facility Name
Novartis Investigative Site
City
Beuvry
ZIP/Postal Code
62660
Country
France
Facility Name
Novartis Investigative Site
City
Ferolles-Attily
ZIP/Postal Code
77150
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier
ZIP/Postal Code
34059
Country
France
Facility Name
Novartis Investigative Site
City
Nantes
ZIP/Postal Code
44000
Country
France
Facility Name
Novartis Investigative Site
City
Pessac
ZIP/Postal Code
33604
Country
France
Facility Name
Novartis Investigative Site
City
Aszod
ZIP/Postal Code
2170
Country
Hungary
Facility Name
Novartis Investigative Site
City
Baja
ZIP/Postal Code
6500
Country
Hungary
Facility Name
Novartis Investigative Site
City
Erd
ZIP/Postal Code
2030
Country
Hungary
Facility Name
Novartis Investigative Site
City
Godollo
ZIP/Postal Code
2100
Country
Hungary
Facility Name
Novartis Investigative Site
City
Makó
ZIP/Postal Code
6900
Country
Hungary
Facility Name
Novartis Investigative Site
City
New Delhi
State/Province
Delhi
ZIP/Postal Code
110029
Country
India
Facility Name
Novartis Investigative Site
City
Banglaore
State/Province
Karnataka
ZIP/Postal Code
560027
Country
India
Facility Name
Novartis Investigative Site
City
Mysore
State/Province
Karnataka
ZIP/Postal Code
570004
Country
India
Facility Name
Novartis Investigative Site
City
Indore
State/Province
Madhya Pradesh
ZIP/Postal Code
452001
Country
India
Facility Name
Novartis Investigative Site
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400007
Country
India
Facility Name
Novartis Investigative Site
City
Dehli
State/Province
New Delhi
ZIP/Postal Code
110063
Country
India
Facility Name
Novartis Investigative Site
City
Coimbatore
State/Province
Tamil Nadu
ZIP/Postal Code
641044
Country
India
Facility Name
Novartis Investigative Site
City
Chennai - Tamil Nadu
ZIP/Postal Code
600 087
Country
India
Facility Name
Novartis Investigative Site
City
Mangalore
Country
India
Facility Name
Novartis Investigative Site
City
Koyang-si
State/Province
Gyeonggi-do
ZIP/Postal Code
410-773
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Busan
ZIP/Postal Code
602-739
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
140-743
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
158-710
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Riga
State/Province
LV
ZIP/Postal Code
LV-1038
Country
Latvia
Facility Name
Novartis Investigative Site
City
Daugavpils
ZIP/Postal Code
LV-5401
Country
Latvia
Facility Name
Novartis Investigative Site
City
Jekabpils
ZIP/Postal Code
LV-5201
Country
Latvia
Facility Name
Novartis Investigative Site
City
Riga
ZIP/Postal Code
1002
Country
Latvia
Facility Name
Novartis Investigative Site
City
Alytus
ZIP/Postal Code
LT-62114
Country
Lithuania
Facility Name
Novartis Investigative Site
City
Kaunas
ZIP/Postal Code
44320
Country
Lithuania
Facility Name
Novartis Investigative Site
City
Klaipeda
ZIP/Postal Code
92288
Country
Lithuania
Facility Name
Novartis Investigative Site
City
Klaipeda
ZIP/Postal Code
LT-92231
Country
Lithuania
Facility Name
Novartis Investigative Site
City
Vilnius
ZIP/Postal Code
06001
Country
Lithuania
Facility Name
Novartis Investigative Site
City
Vilnius
ZIP/Postal Code
LT-08661
Country
Lithuania
Facility Name
Novartis Investigative Site
City
Bucharest
State/Province
District 1
ZIP/Postal Code
011422
Country
Romania
Facility Name
Novartis Investigative Site
City
Bucharest
State/Province
District 1
ZIP/Postal Code
10457
Country
Romania
Facility Name
Novartis Investigative Site
City
Bucharest
State/Province
District 3
ZIP/Postal Code
030303
Country
Romania
Facility Name
Novartis Investigative Site
City
Brasov
State/Province
Jud. Brasov
ZIP/Postal Code
500118
Country
Romania
Facility Name
Novartis Investigative Site
City
Iasi
State/Province
Jud. Iasi
ZIP/Postal Code
700115
Country
Romania
Facility Name
Novartis Investigative Site
City
Pretoria
ZIP/Postal Code
0184
Country
South Africa
Facility Name
Novartis Investigative Site
City
Pretoria
Country
South Africa
Facility Name
Novartis Investigative Site
City
Bath
ZIP/Postal Code
BA1 2SR
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Bath
ZIP/Postal Code
BA2 3HT
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Cambridge
ZIP/Postal Code
CB7 5JD
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Chesterfield
ZIP/Postal Code
S40 4TF
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Glasgow
ZIP/Postal Code
G69 7AD
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Irvine
ZIP/Postal Code
KA12 0AY
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Lancashire
ZIP/Postal Code
FY3 7EN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Watford
ZIP/Postal Code
WD25 0EA
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Wellingborough
ZIP/Postal Code
NN8 4RW
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
25677679
Citation
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.
Results Reference
derived
PubMed Identifier
23867808
Citation
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.
Results Reference
derived
Learn more about this trial
A Study to Assess the Long-term Safety of QVA149
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