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Evaluation of the Efficacy and Safety of QVA149 (110/50 μg o.d.) vs Tiotropium (18 µg o.d.) + Salmeterol/Fluticasone Propionate FDC (50/500 µg b.i.d.) in Patients With Moderate to Severe COPD

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ClinicalTrials.gov Identifier: NCT02603393
Recruitment Status : Completed
First Posted : November 11, 2015
Results First Posted : April 29, 2019
Last Update Posted : April 29, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE September 17, 2015
First Posted Date  ICMJE November 11, 2015
Results First Submitted Date  ICMJE July 9, 2018
Results First Posted Date  ICMJE April 29, 2019
Last Update Posted Date April 29, 2019
Actual Study Start Date  ICMJE November 20, 2015
Actual Primary Completion Date July 18, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 25, 2019)
Mean Change From Baseline in Post-dose Trough FEV1 [ Time Frame: Baseline, 26 weeks ]
Mean change from baseline in post-dose trough forced expiratory volume in 1 second (FEV1) following 26 weeks of treatment. Trough FEV1 is defined as the mean of the two FEV1 values measured at 23 hr 15 min and 23 hr 45 min after the morning dose taken at site on Day 181. Baseline FEV1 is defined as the average of the pre-dose FEV1 measured at -45 min and -15 min at Day 1.
Original Primary Outcome Measures  ICMJE
 (submitted: November 10, 2015)
Post-dose trough FEV1 [ Time Frame: 26 weeks ]
Mean change from baseline in post-dose trough forced expiratory volume in 1 second following 26 weeks of treatment
Change History Complete list of historical versions of study NCT02603393 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2019)
  • Annualized Rate of Moderate or Severe COPD Exacerbations [ Time Frame: 26 weeks ]
    Moderate or severe COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event.
  • Annualized Rate of COPD Exacerbations Requiring Treatment With Systemic Glucocorticosteroids and/or Antibiotics, Moderate Exacerbations Only [ Time Frame: 26 weeks ]
    COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event
  • Annualized Rate of COPD Exacerbations Requiring Hospitalisation [ Time Frame: 26 weeks ]
    COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event.
  • Mean Change From Baseline in Pre-dose Trough FEV1 [ Time Frame: 26 weeks ]
    Trough FEV1 is defined as the average of the pre-dose FEV1 measurements at -45 min and -15 min prior to dosing at each visit except Day 182 which is the average of the post-dose FEV1 measurements at 23h15min and 23h45min after dosing at Day 181. Baseline FEV1 is considered the Day 1 average of pre-dose measurements.
  • Mean Change From Baseline in St. George's Respiratory Questionnaire [ Time Frame: Baseline, 12 weeks ]
    The St. George Respiratory Questionnaire C (SGRQ-C) is used to provide the health status measurements in this study. Baseline SGRQ-C is defined as the assessment taken right before the first dose of the double-blind drug on Day 1. Higher values correspond to greater impairment of health status. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.
  • Mean Change From Baseline in St. George's Respiratory Questionnaire [ Time Frame: Baseline, 26 weeks ]
    The St. George Respiratory Questionnaire C (SGRQ-C) is used to provide the health status measurements in this study. Baseline SGRQ-C is defined as the assessment taken right before the first dose of the double-blind drug on Day 1. Higher values correspond to greater impairment of health status. The SGRQ contains 50 items divided into 2 parts covering 3 aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts", which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.
  • Transition Dyspnea Index (TDI) Score [ Time Frame: 12 weeks ]
    Transitional Dyspnea Index (TDI) score presents the degree of impairment due to dyspnea. The lower the score the worse the severity of dyspnea. The Baseline Dyspnea Index (BDI) / TDI is an instrument used to assess a participant's level of dyspnea. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort. BDI domains were rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranged from 0 to 12; lower scores mean worse severity. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of ≥1 was defined as a clinically important improvement from baseline.
  • Transition Dyspnea Index (TDI) Score [ Time Frame: 26 weeks ]
    Transitional Dyspnea Index (TDI) score presents the degree of impairment due to dyspnea. The lower the score the worse the severity of dyspnea. The Baseline Dyspnea Index (BDI) / TDI is an instrument used to assess a participant's level of dyspnea. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort. BDI domains were rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranged from 0 to 12; lower scores mean worse severity. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of ≥1 was defined as a clinically important improvement from baseline.
  • Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication [ Time Frame: Baseline, 26 weeks ]
    Change from baseline in mean daily number of puffs of rescue medication (number of puffs taken in the previous 12 hours) over 26 weeks of treatment.
  • Mean Change From Baseline in Forced Vital Capacity (FVC) [ Time Frame: Baseline, 26 weeks ]
    Change from baseline in forced vital capacity following 26 weeks of treatment. Trough FVC is defined as the average of the pre-dose FVC measurements at -45 min and -15 min prior to dosing at each visit except Day 182 which is the average of the post-dose FVC measurements at 23h15min and 23h45min after dosing at Day 181. Baseline is considered the Day 1 average of pre-dose measurements.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2015)
  • Rate of moderate to severe COPD exacerbations requiring treatment with systemic glucocorticosteroids and/or antibiotics [ Time Frame: 26 weeks ]
    The rate of moderate to severe COPD exacerbations requiring treatment with systemic glucocorticosteroids and/or antibiotics over 26 weeks of treatment
  • Rate of moderate to severe COPD exacerbations requiring hospitalisation [ Time Frame: 26 weeks ]
    The rate of moderate to severe COPD exacerbations requiring hospitalisation over 26 weeks of treatment
  • Trough FEV1 [ Time Frame: 26 weeks ]
    Trough forced expiratory volume in 1 second over 26 weeks of treatment
  • Total St. George's Respiratory Questionnaire score [ Time Frame: 12 weeks ]
    Total score of the the St. George's Respiratory Questionnaire (SGRQ-C) after 12 weeks of treatment
  • Total St. George's Respiratory Questionnaire score [ Time Frame: 26 weeks ]
    Total score of the the St. George's Respiratory Questionnaire (SGRQ-C) after 26 weeks of treatment
  • Total Transitional Dyspnea Index score [ Time Frame: 12 weeks ]
    Total score of the the Transitional Dyspnea Index (TDI) over 12 weeks of treatment
  • Total Transitional Dyspnea Index score [ Time Frame: 26 weeks ]
    Total score of the the Transitional Dyspnea Index (TDI) over 26 weeks of treatment
  • Number of puffs of rescue medication [ Time Frame: 26 weeks ]
    Mean use of rescue therapy (number of puffs/day) and the percentage of days without rescue therapy over the 26 weeks treatment period
  • HPA axis function [Safety and Tolerability] [ Time Frame: 26 weeks ]
    HPA axis function, as determined by 24-hour weighted mean urine cortisol, in a sub-set of patients
  • Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [ Time Frame: 26 weeks ]
    Number of Participants With Adverse Events That Are Related to Treatment
  • Trough FVC [ Time Frame: 26 weeks ]
    Trough forced vital capacity over 26 weeks
  • Incidence of abnormal laboratory values [Safety and Tolerability] [ Time Frame: 26 weeks ]
    Number of Participants With Abnormal Laboratory Values
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Efficacy and Safety of QVA149 (110/50 μg o.d.) vs Tiotropium (18 µg o.d.) + Salmeterol/Fluticasone Propionate FDC (50/500 µg b.i.d.) in Patients With Moderate to Severe COPD
Official Title  ICMJE A 26-week, Randomized, Double Blind, Parallel-group Multicenter Study to Assess the Efficacy and Safety of QVA149 (110/50 μg o.d.) vs Tiotropium (18 µg o.d.) + Salmeterol/Fluticasone Propionate FDC (50/500 µg b.i.d.) in Patients With Moderate to Severe COPD
Brief Summary This study will evaluate the efficacy and safety of QVA149 (110/50 μg o.d.) vs tiotropium (18 µg o.d.) + salmeterol/fluticasone propionate FDC (50/500 µg b.i.d.) in patients with moderate to severe COPD
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Obstructive Pulmonary Disease (COPD)
Intervention  ICMJE
  • Drug: QVA149
    QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept 1 SDDPI
  • Drug: Tiotropium
    Tiotropium will be supplied as commercially available blisters, delivered via HandiHaler®
  • Drug: Salmeterol/fluticasone
    Salmeterol/fluticasone propionate dry inhalation powder delivered via Accuhaler™
Study Arms  ICMJE
  • Experimental: QVA149
    Intervention: Drug: QVA149
  • Active Comparator: Tiotropium + salmeterol/fluticasone
    Interventions:
    • Drug: Tiotropium
    • Drug: Salmeterol/fluticasone
Publications * Chapman KR, Hurst JR, Frent SM, Larbig M, Fogel R, Guerin T, Banerji D, Patalano F, Goyal P, Pfister P, Kostikas K, Wedzicha JA. Long-Term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in Patients with Chronic Obstructive Pulmonary Disease (SUNSET): A Randomized, Double-Blind, Triple-Dummy Clinical Trial. Am J Respir Crit Care Med. 2018 Aug 1;198(3):329-339. doi: 10.1164/rccm.201803-0405OC.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 26, 2017)
1053
Original Estimated Enrollment  ICMJE
 (submitted: November 10, 2015)
1000
Actual Study Completion Date  ICMJE July 18, 2017
Actual Primary Completion Date July 18, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients who have signed Informed Consent Form prior to initiation of any study-related procedure.
  • Male and female adults aged ≥ 40 years.
  • Patients with moderate to severe airflow obstruction with stable COPD (Stage 2 or Stage 3) according to the 2014 GOLD Guidelines.
  • Patients with a post-bronchodilator FEV1 ≥40 and < 80% of the predicted normal value, and post-bronchodilator FEV1/FVC < 0.70 at run-in Visit 101. (Post refers to 15 min after inhalation of 400 µg of salbutamol).
  • Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack /day x 10 years, or ½ pack/day x 20 years). An ex-smoker is defined as a patient who has not smoked for ≥ 6 months at screening.
  • Patients who are on triple treatment at least for the last 6 months (LAMA +LABA/ICS).

Exclusion Criteria:

  • Patients who have not achieved acceptable spirometry results at Visit 101 in accordance with ATS (American Thoracic Society)/ERS (European Respiratory Society) criteria for acceptability (one retest may be performed for patients that don't meet the acceptability criteria) .
  • Patients who have had more than one COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the last year prior to Visit 1.
  • Patients who developed a COPD exacerbation of any severity either 6 weeks before the screening (Visit 1) or between screening (Visit 1) and treatment (Visit 201) 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.

Other protocol-defined inclusion/exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Bulgaria,   Austria,   Belgium,   Canada,   Croatia,   Czechia,   Denmark,   Estonia,   Germany,   Greece,   Hungary,   Latvia,   Lithuania,   Netherlands,   Poland,   Romania,   Serbia,   Slovakia,   Spain,   United Kingdom
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02603393
Other Study ID Numbers  ICMJE CQVA149A2316
2015-000114-22 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP