QVA vs. Salmeterol/Fluticasone, 52-week Exacerbation Study

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01782326
First received: January 30, 2013
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

This study will assess the efficacy, safety and tolerability of QVA149 in patients with moderate to very severe COPD.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: QVA149
Drug: Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A 52-week Treatment, Multi-center, Randomized, Double-blind, Double Dummy, Parallel-group, Active Controlled Study to Compare the Effect of QVA149 (Indacaterol Maleate / Glycopyrronium Bromide) With Salmeterol/Fluticasone on the Rate of Exacerbations in Subjects With Moderate to Very Severe COPD.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Rate of COPD exacerbations [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The rate of COPD exacerbations over 52 weeks of treatment.


Secondary Outcome Measures:
  • Time to first COPD exacerbation. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The time to the first COPD exacerbation over 52 weeks of treatment.

  • Rate of moderate to severe COPD exacerbations. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The rate of moderate to severe COPD exacerbations during 52 weeks of treatment.

  • Time to first moderate to severe COPD exacerbation. [ Time Frame: 52 weeks. ] [ Designated as safety issue: No ]
    The time to the first moderate to severe COPD exacerbation over 52 weeks of treatment.

  • Rate of moderate to severe COPD exacerbations requiring treatment with systemic corticosteroids [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The rate of moderate to severe COPD exacerbations requiring treatment with systemic corticosteroids over 52 weeks of treatment.

  • Rate of moderate to severe COPD exacerbations requiring treatment with antibiotics [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The rate of moderate to severe COPD exacerbations requiring treatment with antibiotics during 52 weeks of treatment.

  • Rate of moderate to severe COPD exacerbations requiring hospitalization. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The rate of moderate to severe COPD exacerbations requiring hospitalization during 52 weeks of treatment.

  • Rate of moderate to severe COPD exacerbations requiring re-hospitalization within 30 days [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The rate of moderate to severe COPD exacerbations requiring re-hospitalization within 30 days, during the 52 week treatment period.

  • Time to first moderate to severe COPD exacerbations requiring treatment with systemic corticosteroids [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    The time to first moderate to severe COPD exacerbation requiring treatment with systemic corticosteroids during 52 week of treatment.

  • Time to first moderate to severe COPD exacerbations requiring treatment with antibiotics [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Time to first COPD exacerbation requiring treatment with antibiotics during 52 weeks of treatment.

  • Time to first moderate to severe COPD exacerbations requiring hospitalization [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Time to first moderate to severe COPD exacerbation requiring hospitalization during 52 weeks of treatment.

  • Time to first moderate to severe COPD exacerbations requiring re-hospitalization within 30 days [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Time to first moderate to severe COPD exacerbation requiring re-hospitalization within 30 days, during 52 weeks of treatment.

  • Forced expiratory volume in 1 second [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    Pre-dose trough Forced expiratory volume in 1 second (mean of 23 hours 15 min and 24 hours 45 min) after 1 day of treatment.

  • Forced expiratory volume in 1 second [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Pre-dose forced expiratory volume in 1 second following 4 weeks of treatment.

  • Forced expiratory volume in 1 second [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Pre-dose trough forced expiratory volume in 1 second following 12 weeks of treatment.

  • Forced expiratory volume in 1 second [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Pre-dose trough Forced expiratory volume in 1 second following 26 weeks of treatment.

  • Forced expiratory volume in 1 second [ Time Frame: 38 weeks ] [ Designated as safety issue: No ]
    Pre-dose trough Forced expiratory volume in 1 second following 38 weeks of treatment.

  • Forced expiratory volume in 1 second [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Pre-dose trough Forced expiratory volume in 1 second following 52 weeks of treatment.

  • Forced expiratory volume in 1 second AUC (0-12h) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Forced expiratory volume in 1 second Area Under the Curve (0-12 hours) following 52 weeks of treatment.

  • Total St. George's Respiratory Questionnaire score [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Change in health status as reported by patients using the St. George's Respiratory Questionnaire (SGRQ-C), following 4 weeks of treatment.

  • Total St. George's Respiratory Questionnaire score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Change in health status as reported by patients using the St. George's Respiratory Questionnaire (SGRQ-C), following 12 weeks of treatment.

  • Total St. George's Respiratory Questionnaire score [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]
    Change in health status as reported by patients using the St. George's Respiratory Questionnaire (SGRQ-C), following 26 weeks of treatment.

  • Total St. George's Respiratory Questionnaire score [ Time Frame: 38 weeks ] [ Designated as safety issue: No ]
    Change in health status as reported by patients using the St. George's Respiratory Questionnaire (SGRQ-C), following 38 weeks of treatment.

  • Total St. George's Respiratory Questionnaire score [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Change in health status as reported by patients using the St. George's Respiratory Questionnaire (SGRQ-C), following 52 weeks of treatment.

  • Number of puffs of rescue medication [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Rescue medication use (number of puffs) reported by the patients using patient electronic diary following 52 weeks of treatment.


Estimated Enrollment: 3332
Study Start Date: July 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QVA149 Drug: QVA149
QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept 1 SDDPI.
Active Comparator: Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS) Drug: Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS)
Salmeterol/fluticasone dry inhalation powder delivered via the Accuhaler device.

  Eligibility

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

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed
  • Male or female adults aged ≥40 years
  • Patients with stable Chronic Obstructive Pulmonary Disease ( COPD) according to the current GOLD strategy (GOLD 2011)
  • Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years)
  • Patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥25 and < 60% of the predicted normal value, and post-bronchodilator FEV1/FVC (Forced Vital Capacity) < 0.70 at day -28. (Post refers to 1 hour after sequential inhalation of 84 µg (or equivalent dose) of ipratropium bromide and 400 µg of salbutamol)
  • A documented history of at least 1 COPD exacerbation in the previous 12 months that required treatment with systemic glucocorticosteroids and/or antibiotics
  • Patients taking stable COPD medication (at least 60 days) prior to day 28
  • Patients with an mMRC grade of at least 2 at day 28

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 hCG (human Chorionic Gonadotropin) laboratory test
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
  • Patients with Type I or uncontrolled Type II diabetes
  • Patients with a history of long QT syndrome or whose QTc measured at day 28 (Fridericia method) is prolonged (>450 ms for males and females) and confirmed by a central assessor. These patients should not be re-screened
  • Patients who have a clinically significant ECG abnormality prior to randomization. (These patients should not be re-screened)
  • Patients who have a clinically significant laboratory abnormality at screening
  • Patients who have clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial infarction), arrhythmia (see below for patients with atrial fibrillation), neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment
  • Patients with paroxysmal (e.g. intermittent) atrial fibrillation are excluded
  • Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., selective beta blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such patients, atrial fibrillation must be present at both pre-randomization visits, with a resting ventricular rate < 100/min. At screening the atrial fibrillation must be confirmed by central reading
  • Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof: anticholinergic agents, long and short acting beta-2 agonists, sympathomimetic amines, lactose or any of the other excipients of trial medication
  • Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
  • Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. Benign Prostatic Hyperplasia (BPH) patients who are stable on treatment can be considered
  • Patients who have not achieved an acceptable spirometry results at screening in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria for acceptability (one retest may be performed for patients that don't meet the acceptability criteria)
  • Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to screening
  • Patients who develop a COPD exacerbation of any severity (mild/moderate/severe) between screening and treatment will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation
  • Patients who have had a respiratory tract infection within 4 weeks prior to screening
  • Patients who develop a respiratory tract infection between screening and prior to treatment will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection
  • Patients requiring long term oxygen therapy prescribed for >12 hours per day
  • Patients with any history of asthma
  • Patients with an onset of respiratory symptoms, including a COPD diagnosis prior to age 40 years
  • Patients with a blood eosinophil count > 600/mm3 at screening
  • Patients with allergic rhinitis who use a H1 antagonist or intra-nasal corticosteroids intermittently (treatment with a stable dose or regimen is permitted)
  • Patients with concomitant pulmonary disease (e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension)
  • Patients with clinically significant bronchiectasis
  • Patients with a diagnosis of α-1 anti-trypsin deficiency
  • Patients with active pulmonary tuberculosis, unless confirmed by imaging to be no longer active
  • Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation
  • Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study. (Maintenance program is permitted.)
  • Patients receiving any medications in the classes listed in the protocol
  • Patients receiving any COPD related medications in the classes specified in the protocol must undergo the required washout period prior to screening and follow the adjustment to treatment program
  • Use of other investigational drugs/devices (approved or unapproved) at the time of enrollment, or within 30 days or 5 half-lives of screening, whichever is longer
  • Patients unable to use an electronic patient diary and EXACT pro diary
  • Patients unable to use a dry powder inhaler device, Metered Dose Inhaler (MDI) or a pressurized MDI (rescue medication) or comply with the study regimen.
  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: NCT01782326

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

  Show 573 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: NCT01782326     History of Changes
Other Study ID Numbers: CQVA149A2318
Study First Received: January 30, 2013
Last Updated: June 2, 2014
Health Authority: European Union: European Medicines Agency

Keywords provided by Novartis:
COPD, QVA149

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Fluticasone
Salmeterol
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Allergic Agents
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Dermatologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014