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Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BEACON)

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ClinicalTrials.gov Identifier: NCT01529632
Recruitment Status : Completed
First Posted : February 9, 2012
Results First Posted : February 12, 2014
Last Update Posted : February 12, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE February 6, 2012
First Posted Date  ICMJE February 9, 2012
Results First Submitted Date  ICMJE December 2, 2013
Results First Posted Date  ICMJE February 12, 2014
Last Update Posted Date February 12, 2014
Study Start Date  ICMJE May 2012
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2014)
Trough Forced Expiratory Volume in 1 Second (FEV1) After 28 Days of Blinded Treatment [ Time Frame: Day 29 ]
Spirometry was conducted according to internationally accepted standards. Trough FEV1 is defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings measured at day 29, after 28 days of treatment. Mixed model: Trough 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 8, 2012)
Trough Forced Expiratory Volume in 1 Second (FEV1) After 28 Days of Blinded Treatment [ Time Frame: 28 days ]
Spirometry will be conducted according to internationally accepted standards. Trough FEV1 is defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings. The mixed model will contain treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilator, FEV1 post inhalation of short acting bronchodilator as covariates. This model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.
Change History Complete list of historical versions of study NCT01529632 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2014)
  • Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 1 [ Time Frame: 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 1 ]
    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.
  • Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4 Hours at Day 28 [ Time Frame: 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose at Day 28 ]
    Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 28 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.
  • Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 28 Post-dose [ Time Frame: 5 min - 4 hr at Days 1 and 28 ]
    Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in the period between 5 minutes and 4 hours post dose. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate.
  • Time Course of Forced Expiratory Volume in One Second (FEV1) (Pre-dose to 4 Hours Post Dose) on Day 28 [ Time Frame: -45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr post-dose on Day 28 ]
    Time course of Forced Expiratory Volume in 1 second (FEV1) was measured at -45 min, -15 min predose, 5 min, 30 min, 1 hr, 2hr, 3hr and 4 hr post-dose on Day 28. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation.
  • Change From Baseline in the Mean Daily, (Daytime and Nighttime Combined) Number of Puffs of Rescue Medication Used Over 28 Days of Treatment [ Time Frame: Baseline and 28 days ]
    The number of puffs of rescue medication taken in the previous 12 hours was recorded in the Patient Diary in the morning and evening. The total number of puffs of rescue medication per day over the whole active treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening) then a half day was used in the denominator.
  • Change From Baseline in Percentage of Days With 'no Daytime Symptoms' Over 28 Days of Treatment [ Time Frame: 28 days ]
    The mean total symptom scores and mean individual symptom scores for the patient were calculated for the whole study period. The mean change from baseline in the total scores and in the individual scores were summarized by treatment and were analyzed for the percentage of 'nights with no nighttime awakenings'. The symptom variables for the whole active treatment period was analyzed using the similar MIXED model as for the primary endpoint, with the baseline FEV1 term being replaced by the respective baseline symptom variables.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 8, 2012)
  • Change From Baseline in the Mean Number of Puffs Per Day of Rescue Medication Over the Study Duration (Baseline to Day 28) [ Time Frame: 28 days ]
    Patients will record the number of puffs of rescue medication in the past 12 hours each morning and evening in the diary. The number of puffs per day during active treatment will be calculated and divided by the total number of days with non-missing data to derive the mean daily number of puffs. If the number of puffs is missing for part of the day then a half day will be used in the denominator. Rescue med use during run-in will be used as baseline. The mean change from baseline will be analyzed using the same MIXED model as primary analysis with baseline daily rescue use replacing FEV1.
  • Change From Baseline in the Mean Number of Puffs of Rescue Medication During the Daytime and Nighttime Over the Study Duration (Baseline to Day 28) [ Time Frame: 28 days ]
    The daytime and nighttime rescue medication use in terms of number of puffs will be calculated in a similar way as for the daily rescue medication use. Change from baseline in the mean daytime and nighttime number of puffs of rescue medication will be analyzed as for the change from baseline in the mean daily number of puffs of rescue medication.
  • Percentage of Days With No Puffs of Rescue Medication During the Daytime and Nighttime Over the Study Duration (Baseline to Day 28) [ Time Frame: 28 days ]
    A 'day with no rescue use' is defined from diary data as any day where the patient has taken no puffs of rescue medication. The percentage of 'days with no rescue use' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
  • Percentage of Nights With no Nighttime Awakenings Over the 28 Day Treatment Period [ Time Frame: 28 days ]
    A night with 'no nighttime awakenings' is defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the whole treatment period will be divided by the total number of nights where diary recordings have been made in order to derive the percentage nights with 'no nighttime awakenings'.
  • Percentage of Days With no Daytime Symptoms Over the 28 Day Treatment Period [ Time Frame: 28 days ]
    A day with 'no daytime symptoms' is defined from the diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours. However, a patient will not be considered symptom free if they have used rescue medication that day even if his/her total daytime symptoms score is zero. The percentage of days with 'no daytime symptoms' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
  • Percentage of Days Able to Perform Usual Daily Activities Over the 28 Day Treatment Period [ Time Frame: 28 days ]
    A 'day able to perform usual daily activities' is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The percentage of 'days able to perform usual daily activities' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
  • Mean Daily Total Symptom Score Over the 28 Day Treatment Period [ Time Frame: 28 days ]
    The mean total symptom scores and mean individual symptom scores for the patient will be calculated for the whole study period. Total score is based on diary entry with total daily score range of 0-54, with 54 being the maximum symptom score. The mean change from baseline in the total scores and in the individual scores will be summarized by treatment and will be analyzed as for the percentage of 'nights with no nighttime awakenings'.
  • Number of Participants With Adverse Events, Death, and Serious or Clinically Significant Adverse Events or Related Discontinuations [ Time Frame: 28 days and 30 day follow-up period ]
    Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
  • Safety and tolerability [ Time Frame: 28 days ]
    Data from the ECGs will be summarized by treatment at all time. Vital signs (blood pressure and radial pulse rate) data will be summarized by treatment at 35 min pre-dose and 1 h post-dose time points at Visit 2, 3, and 5. All lab data will be listed with abnormal values flagged. The lab values and the change from baseline for continuous lab parameters will be summarized at each visit. A frequency table of results for categorical lab parameters will be produced by visit. Shift tables relative to normal ranges will be used to summarize the change from baseline to post-baseline by visit.
  • FEV1 AUC 0-4h at Day 1 and Day 28 [ Time Frame: Day 1 and Day 28 ]
    Spirometry will be conducted according to internationally accepted standards. FEV1 was measured at 45 and 15 minutes pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, and at 23 h 15 min and 23 h 45 min post dose, by visit. The mixed model will contain treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilator, FEV1 post inhalation of short acting bronchodilator as covariates. This model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official Title  ICMJE A Study to Compare the Efficacy and Safety of Once Daily QVA149 Versus the Once Daily Concurrent Administration of QAB149 Plus NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease
Brief Summary The study assessed the safety and efficacy of the fixed combination product QVA149 versus the component products QAB149 and NVA237, administered concurrently, in patients that have moderate to severe chronic obstructive pulmonary disease (COPD).
Detailed Description The study assessed the safety and efficacy of the fixed combination product QVA149 versus the component products QAB149 and NVA237, administered concurrently, in patients that have moderate to severe chronic obstructive pulmonary disease (COPD).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
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
Intervention  ICMJE
  • Drug: QVA149
    QVA149 110/50 ug supplied as capsules in blister packs for inhalation via SDDPI, once daily
  • Drug: NVA237
    NVA237 50 ug supplied as capsules in blister packs for inhalation via SDDPI, once daily
  • Drug: QAB149
    QAB149 150 ug supplied as capsules in blister packs for inhalation via SDDPI , once daily
  • Drug: Placebo
    Placebo capsules provided in blister packs for inhalation via SDDPI, once daily
Study Arms  ICMJE
  • Experimental: QVA149
    QVA149 plus placebo once daily for 28 days.
    Interventions:
    • Drug: QVA149
    • Drug: Placebo
  • Active Comparator: QAB149 + NVA237
    Indacaterol maleate (QAB149) plus glycopyrronium bromide (NVA237) once daily for 28 days.
    Interventions:
    • Drug: NVA237
    • Drug: QAB149
Publications * Not Provided

*   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: January 16, 2014)
193
Original Estimated Enrollment  ICMJE
 (submitted: February 8, 2012)
184
Actual Study Completion Date  ICMJE December 2012
Actual Primary Completion Date December 2012   (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 COPD (moderate to severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2010)
  • Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) < 70%

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 Child, 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 Austria,   Denmark,   Netherlands,   Norway,   Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01529632
Other Study ID Numbers  ICMJE CQVA149A2326
2011-006050-91 ( 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 2014

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