A 26-week Treatment Randomized, Double-blind, Double Dummy Study to Assess the Efficacy and Safety of QVA149

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01709903
First received: October 16, 2012
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

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


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: QVA149
Drug: Fluticasone/salmeterol
Drug: Pacebo to QVA149
Drug: Placebo to fluticasone/salmeterol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Trough Forced Expiratory Volume in one second (FEV1) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose


Secondary Outcome Measures:
  • Standardized Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC) 0-12 hours [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]
    The trapezoidal rule will be used to calculate Forced Expiratory Volume in one second Area under the curve.

  • Trough Forced Expiratory Volume in one second (FEV1) and Forced Vital Capacity (FVC) [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]
    Average of Trough Forced Expiratory Volume in one second (FEV1) and Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose

  • Standardized Forced Expiratory Volume in one second (FEV1) Area under the curve (AUC) 0-4 hours [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]
    The trapezoidal rule will be used to calculate Forced Expiratory Volume in one second Area under the curve.

  • Health Related Quality of Life [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]
    The total score of St.George Respiratory Questionnaire (SGRQ)

  • Dyspnea [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]
    Dyspnea will be measured at baseline using the baseline dyspnea index (BDI) and during the treatment period using the transitional dyspnea index (TDI), which captures changes from baseline.

  • Rescue medication use [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]
    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.

  • Symptoms reported using e-diary over 12 and 26 weeks of treatment [ Time Frame: 12 and 26 weeks ] [ Designated as safety issue: No ]
    Will be recorded in the Patient Diary in the morning and evening

  • Safety and tolerability [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
    Electrocardiograms(ECGs), laboratory tests, blood pressure, heart rate and adverse events including Chronic Obstructive Pulmonary Disease (COPD) exacerbations and oral candidiasis.


Enrollment: 747
Study Start Date: November 2012
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: QVA149
QVA149 110/50 µg capsules q.d. for inhalation, delivered via Novartis single dose dry powder inhaler (SDDPI).
Other Name: Experimental: QVA149
Drug: Placebo to fluticasone/salmeterol
Placebo to fluticasone/salmeterol with Accuhaler
Other Name: Comparator: fluticasone/salmeterol
Active Comparator: fluticasone/salmeterol
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Drug: Fluticasone/salmeterol
Active fluticasone/salmeterol (500/50µg) b.i.d via a dry power inhaler Accuhaler® device.
Other Name: Comparator: Fluticasone/salmeterol
Drug: Pacebo to QVA149
Placebo to QVA149 with SDDPI
Other Name: Experimental: QVA149

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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709903

  Show 56 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01709903     History of Changes
Other Study ID Numbers: CQVA149A2331
Study First Received: October 16, 2012
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Argentina: Human Research Bioethics Committee
Argentina: Ministry of Health
Brazil: Ethics Committee
Brazil: Ministry of Health
Brazil: National Committee of Ethics in Research
Brazil: National Health Surveillance Agency
Chile: Comisi?n Nacional de Investigaci?n Cient?fica y Tecnol?gica
Chile: Instituto de Salud Pública de Chile
China: Ethics Committee
China: Ministry of Health
China: Food and Drug Administration
Taiwan: Center for Drug Evaluation
Taiwan: Department of Health
Taiwan: Institutional Review Board
Taiwan: National Bureau of Controlled Drugs

Keywords provided by Novartis:
chronic obstructive pulmonary disease

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Fluticasone
Salmeterol
Albuterol
Fluticasone, salmeterol drug combination
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Dermatologic Agents
Anti-Allergic Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Tocolytic Agents
Reproductive Control Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 18, 2014