- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01709903
A 26-week Treatment Randomized, Double-blind, Double Dummy Study to Assess the Efficacy and Safety of QVA149
A 26-week Treatment Randomized, Double-blind, Double Dummy, Parallel-group Study to Assess the Efficacy and Safety of QVA149 (Indacaterol / Glycopyrronium Bromide) Compared to Fluticasone/Salmeterol in Patients With Moderate to Severe COPD
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50 µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.
The study population will consist of approximate 736 male and female adults (age 40 years and greater) with a clinical diagnosis of stable COPD [GOLD (2010)] and a smoking history of at least 10 pack years. It is anticipated that approximately 981 patients will need to be screened in order to randomize 736 patients into 2 treatment arms of the study with an equal randomization ratio, meaning QVA149 (368 patients), fluticasone/salmeterol (368 patients). Treatment randomization will be stratified by current/ex-smoker status and prior ICS use. It is intended that 552 patients will complete the study at Week 26 without major protocol deviations. Dropouts will not be replaced.
This will be a multi-national study, including China, and at least two other countries.
Standardization FEV1 AUC0-12h will be performed in a subgroup of around 100 patients (50 patients per treatment arm) in pre-selected centers.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Buenos Aires, Argentina, C1125ABE
- Novartis Investigative Site
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Cordoba, Argentina, X5016KEH
- Novartis Investigative Site
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Buenos Aires
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Caba, Buenos Aires, Argentina, C1280AEB
- Novartis Investigative Site
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Caba, Buenos Aires, Argentina, C1056ABJ
- Novartis Investigative Site
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Caba, Buenos Aires, Argentina, C1425BEN
- Novartis Investigative Site
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Caba, Buenos Aires, Argentina, 1122
- Novartis Investigative Site
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Caba, Buenos Aires, Argentina, C1424BSF
- Novartis Investigative Site
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Caba, Buenos Aires, Argentina, B8000XAV
- Novartis Investigative Site
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La Plata, Buenos Aires, Argentina, 1900
- Novartis Investigative Site
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Mar del Plata, Buenos Aires, Argentina, 7600
- Novartis Investigative Site
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Rojas, Buenos Aires, Argentina, B2705XAE
- Novartis Investigative Site
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Tucuman
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San Miguel de Tucuman, Tucuman, Argentina, T4000IFL
- Novartis Investigative Site
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Santiago, Chile
- Novartis Investigative Site
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Santiago, Chile, PISO 1
- Novartis Investigative Site
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Region Metropolitana
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Santiago, Region Metropolitana, Chile, 8431633
- Novartis Investigative Site
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Santiago, Region Metropolitana, Chile
- Novartis Investigative Site
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Vina del Mar
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Viña del Mar, Vina del Mar, Chile, 2520024
- Novartis Investigative Site
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Beijing, China, 100029
- Novartis Investigative Site
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Beijing, China, 100020
- Novartis Investigative Site
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Beijing, China, 100034
- Novartis Investigative Site
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Beijing, China, 100050
- Novartis Investigative Site
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Beijing, China
- Novartis Investigative Site
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Chongqing, China, 400037
- Novartis Investigative Site
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Chongqing, China, 400038
- Novartis Investigative Site
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Chongqing, China, 400042
- Novartis Investigative Site
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Jiangyin, China
- Novartis Investigative Site
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Nanjing, China
- Novartis Investigative Site
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Shanghai, China, 200080
- Novartis Investigative Site
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Shanghai, China, 200032
- Novartis Investigative Site
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Shanghai, China, 200433
- Novartis Investigative Site
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Beijing
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Beijing, Beijing, China, 100730
- Novartis Investigative Site
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Beijing, Beijing, China, 100023
- Novartis Investigative Site
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Guangxi
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Nanning, Guangxi, China, 530021
- Novartis Investigative Site
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Hebei
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Shijiazhuang, Hebei, China, 050000
- Novartis Investigative Site
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Hubei
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Wuhan, Hubei, China, 430022
- Novartis Investigative Site
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Hunan
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Changsha, Hunan, China, 410003
- Novartis Investigative Site
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Changsha City, Hunan, China, 410011
- Novartis Investigative Site
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Jiangsu
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Nanjing, Jiangsu, China, 210029
- Novartis Investigative Site
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Suzhou, Jiangsu, China, 215004
- Novartis Investigative Site
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Jiangxi
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Nanchang, Jiangxi, China, 330006
- Novartis Investigative Site
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Liaoning
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Shengyang, Liaoning, China, 110016
- Novartis Investigative Site
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Shenyang, Liaoning, China
- Novartis Investigative Site
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Shandong
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Qingdao, Shandong, China, 266011
- Novartis Investigative Site
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Shanghai
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Shanghai, Shanghai, China, 200433
- Novartis Investigative Site
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Shanxi
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Xi'an, Shanxi, China, 710032
- Novartis Investigative Site
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Xi'an, Shanxi, China, 710061
- Novartis Investigative Site
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Sichuan
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Chengdu, Sichuan, China, 610041
- Novartis Investigative Site
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Zhejiang
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Hangzhou, Zhejiang, China, 310016
- Novartis Investigative Site
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Hangzhou, Zhejiang, China, 310003
- Novartis Investigative Site
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Hangzhou, Zhejiang, China, 310006
- Novartis Investigative Site
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Kaohsiung, Taiwan, 81346
- Novartis Investigative Site
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Lin-Ko, Taiwan, 33305
- Novartis Investigative Site
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Niaosong Township, Taiwan, 83301
- Novartis Investigative Site
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Taichung, Taiwan, 40705
- Novartis Investigative Site
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Taipei County, Taiwan
- Novartis Investigative Site
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Taiwan, ROC
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Taipei, Taiwan, ROC, Taiwan, 112
- Novartis Investigative Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patients with moderate to severe stable COPD (Stage II or Stage III) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guideline.
Current or ex-smokers who have a smoking history of at least 10 pack years. Patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥ 30% and < 80% of the predicted normal, and post-bronchodilator FEV1/FVC < 0.7.
Modified Medical Research Council (mMRC) grade of at least 2 at Visit 2.
Exclusion Criteria:
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin (hCG) laboratory test.
Patents with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH), bladder-neck obstruction, moderate to severe renal impairment or urinary retention. BPH patients who are stable on treatment can be considered.
Patients with a history of long QT syndrome or whose QTc measured at run-in (Visit 2) (Fridericia method) is prolonged (>450 ms for males and females) as confirmed by the central Electrocardiogram (ECG) assessor.
Patients with Type I or uncontrolled Type II diabetes. Patients who have not achieved spirometry result at Visit 2 in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria for acceptability and repeatability.
Patients with, a) any history of asthma or, b) onset of respiratory symptoms prior to age 40 years.
Patients with concomitant pulmonary disease (e.g. lung fibrosis, primary bronchiectasis, sarcoidosis, interstitial lung disorder, pulmonary hypertension).
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
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: QVA149
QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg
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QVA149 110/50 µg capsules q.d. for inhalation, delivered via Novartis single dose dry powder inhaler (SDDPI).
Other Names:
Placebo to fluticasone/salmeterol with Accuhaler
Other Names:
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Active Comparator: fluticasone/salmeterol
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
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Active fluticasone/salmeterol (500/50µg) b.i.d via a dry power inhaler Accuhaler® device.
Other Names:
Placebo to QVA149 with SDDPI
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
Time Frame: 26 weeks
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Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.
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26 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
Time Frame: 26 weeks
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26 weeks
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Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours
Time Frame: Day 1, 12 and 26 weeks
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Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards.
Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose.
The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time.
Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error.
Center was included as a random effect nested within country.
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Day 1, 12 and 26 weeks
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Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period
Time Frame: 6,12,18 and 26 weeks
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Average of Trough Forced Expiratory Volume in one second (FEV1)
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6,12,18 and 26 weeks
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Analysis of Trough FVC (L) Over the Whole Treatment Period
Time Frame: 12 and 26 weeks
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Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose
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12 and 26 weeks
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Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment
Time Frame: 26 weeks
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A Total and three component scores are calculated: Symptoms; Activity; Impacts.
Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8
Total (sum of maximum for all three components) 3201.9
The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed.
The higher the score the more symptoms of disease are present.
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26 weeks
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Analysis of the TDI Focal Score Over the Whole Treatment Period
Time Frame: 12 and 26 weeks
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The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9.
The lower the score, the more deterioration in severity of dyspnea.
One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea.
."Baseline
12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point.
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12 and 26 weeks
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Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals
Time Frame: 12 and 26 weeks
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The number of puffs of rescue medication taken in the previous 12 hours will be recorded in the Patient Diary in the morning and evening.
"Baseline 12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point.
Less puffs taken is better.
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12 and 26 weeks
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Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment
Time Frame: 26 weeks
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Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS)
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26 weeks
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Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Zhong N, Wang C, Zhou X, Zhang N, Humphries M, Wang L, Patalano F, Banerji D. Efficacy and Safety of Indacaterol/Glycopyrronium (IND/GLY) Versus Salmeterol/Fluticasone in Chinese Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease: The Chinese Cohort from the LANTERN Study. COPD. 2016 Dec;13(6):686-692. doi: 10.1080/15412555.2016.1182970. Epub 2016 Aug 11.
- Zhong N, Wang C, Zhou X, Zhang N, Humphries M, Wang L, Thach C, Patalano F, Banerji D; LANTERN Investigators. LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2015 Jun 5;10:1015-26. doi: 10.2147/COPD.S84436. eCollection 2015.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Anti-Inflammatory Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Adrenergic Agonists
- Dermatologic Agents
- Adjuvants, Anesthesia
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Anti-Allergic Agents
- Adrenergic beta-2 Receptor Agonists
- Adrenergic beta-Agonists
- Sympathomimetics
- Fluticasone
- Xhance
- Salmeterol Xinafoate
- Fluticasone-Salmeterol Drug Combination
- Glycopyrrolate
Other Study ID Numbers
- CQVA149A2331
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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