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Efficacy and Safety Study of QVA149 in COPD Patients

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ClinicalTrials.gov Identifier: NCT02487446
Recruitment Status : Completed
First Posted : July 1, 2015
Results First Posted : December 26, 2017
Last Update Posted : December 26, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE June 29, 2015
First Posted Date  ICMJE July 1, 2015
Results First Submitted Date  ICMJE September 12, 2017
Results First Posted Date  ICMJE December 26, 2017
Last Update Posted Date December 26, 2017
Actual Study Start Date  ICMJE July 28, 2015
Actual Primary Completion Date September 12, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2017)
Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h [ Time Frame: baseline, 0 to 24 hours post-dose at week 12 ]
FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-24h). A positive change from baseline indicates improvement.
Original Primary Outcome Measures  ICMJE
 (submitted: June 29, 2015)
To demonstrate non-inferiority of QVA149 compared to umeclidinium/vilanterol in terms of FEV1 AUC 0-24h [ Time Frame: 12 weeks ]
FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-24h).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 30, 2017)
  • Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h [ Time Frame: baseline, 0 to 24 hours post-dose at week 12 ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over an entire day (AUC 0-24h). A positive change from baseline indicates improvement.
  • Change From Baseline in Trough FEV1 (Mean of 23h 15 Minutes and 23 h 45 Minutes Post Previous Morning Dose) [ Time Frame: baseline, 23 hours 15 minutes and 23 hours 45 minutes post previous morning dose at week 12 ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose for each treatment
  • Change From Baseline in FEV1 AUC 12-24h [ Time Frame: baseline, 12 hours to 24 hours post-dose at week 12 ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over 12 hours (AUC 12-24h).
  • Change From Baseline in FEV1 AUC 0-12h [ Time Frame: baseline, 0 to 12 hours post-dose at week 12 ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over 12 hours (AUC 0-12h).
  • Change From Baseline in FEV1 AUC 0-4h, AUC 4-8h, AUC 8-12h, AUC 12-16h, AUC 16-20h and AUC 20-24h [ Time Frame: baseline, 12 weeks ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time over 4 hour intervals FEV1 AUC 0-4h, AUC 4-8h, AUC 8-12h, AUC 12-16h, AUC 16-20h and AUC 20-24h.
  • Change From Baseline in Pre-dose Trough FEV1 (Mean of 15 Minutes and 45 Minutes Pre Morning Dose) [ Time Frame: baseline, 15 minutes and 45 minutes pre morning dose at week 12 ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Pre-dose trough FEV1 was defined as the average of measurements made 15 minutes and 45 minutes pre morning dose for each treatment.
  • QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in FEV1 at Any Time Point [ Time Frame: Day 1 (5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 23h 15min, 23h 45min); week 6 (-45min, -15min); week 12 (-45min, -15min, 5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 12h 5min, 12h 15min, 12h 30min, 13, 14, 16, 20, 23h 15min, 23h 45min) ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards.
  • QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in Forced Vital Capacity (FVC) at Any Time Point [ Time Frame: Day 1 (5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 23h 15min, 23h 45min); week 6 (-45min, -15min); week 12 (-45min, -15min, 5min, 15min, 30min, hours 1, 2, 4, 8, 11h 55min, 12h 5min, 12h 15min, 12h 30min, 13, 14, 16, 20, 23h 15min, 23h 45min) ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2015)
  • To demonstrate the superiority of QVA149 compared to umeclidinium/vilanterol in terms of FEV1 AUC 0-24h [ Time Frame: 12 weeks ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards over an entire day (AUC 0-24h).
  • To demonstrate the superiority of QVA149 compared to umeclidinium/vilanterol in terms of trough FEV1 (mean of 23h 15 min and 23 h 45 min post previous morning dose) [ Time Frame: 12 weeks ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 15 minutes and 23 hours 45 minutes post-dose for each treatment
  • To demonstrate the superiority of QVA149 compared to umeclidinium/vilanterol in terms of FEV1 AUC 12-24h [ Time Frame: 12 weeks ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards from 12 to 24h (AUC)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of QVA149 in COPD Patients
Official Title  ICMJE A Multi-center, Randomized, Double-blind, Double-dummy, Active Controlled, 2-period Cross-over Study to Assess the Efficacy, Safety and Tolerability of Indacaterol Maleate/Glycopyrronium Bromide Compared to Umeclidinium Bromide/Vilanterol in COPD Patients With Moderate to Severe Airflow Limitation
Brief Summary The purpose of this study is to demonstrate that the efficacy of the combination product QVA149 is similar to the efficacy of the combination product umeclidinium/vilanterol on a pre-specified endpoint of FEV1 AUC0-24h while maintaining an acceptable safety profile.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic Obstructive Pulmonary Disease
Intervention  ICMJE
  • Drug: QVA149
    QVA149 capsules for inhalation, delivered via QVA149 single dose dry powder inhaler (SDDPI)
    Other Name: Indecaterol maleate/glycopyrronium bromide
  • Drug: Umeclidinium/vilanterol
    Umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler
    Other Name: ELLIPTA®
  • Drug: Placebo (umeclidinium/vilanterol)
    Matching Placebo to umeclidinium/vilanterol for inhalation, delivered via ELLIPTA® inhaler
  • Drug: Placebo (QVA149)
    Matching Placebo to QVA149 capsules for inhalation, delivered via QVA149 SDDPI
Study Arms  ICMJE
  • Experimental: First QVA149, then Umeclidinium/vilanterol
    Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Then after 3 weeks washout, participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
    Interventions:
    • Drug: QVA149
    • Drug: Umeclidinium/vilanterol
    • Drug: Placebo (umeclidinium/vilanterol)
    • Drug: Placebo (QVA149)
  • Experimental: First Umeclidinium/vilanterol, then QVA149
    Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks. Then after 3 weeks washout, participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
    Interventions:
    • Drug: QVA149
    • Drug: Umeclidinium/vilanterol
    • Drug: Placebo (umeclidinium/vilanterol)
    • Drug: Placebo (QVA149)
Publications * Kerwin E, Ferguson GT, Sanjar S, Goodin T, Yadao A, Fogel R, Maitra S, Sen B, Ayers T, Banerji D. Dual Bronchodilation with Indacaterol Maleate/Glycopyrronium Bromide Compared with Umeclidinium Bromide/Vilanterol in Patients with Moderate-to-Severe COPD: Results from Two Randomized, Controlled, Cross-over Studies. Lung. 2017 Dec;195(6):739-747. doi: 10.1007/s00408-017-0055-9. Epub 2017 Oct 9.

*   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: November 30, 2017)
357
Original Estimated Enrollment  ICMJE
 (submitted: June 29, 2015)
354
Actual Study Completion Date  ICMJE September 12, 2016
Actual Primary Completion Date September 12, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female adults aged ≥40 yrs
  • Smoking history of at least 10 pack years
  • Diagnosis of stable Chronic Obstructive Pulmonary Disease (COPD) as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2015)
  • Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)< 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) <70%
  • Modified Medical Research Council questionnaire grade of 2 or higher

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
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02487446
Other Study ID Numbers  ICMJE CQVA149A2349
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date November 2017

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