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Trial record 13 of 318 for:    FLUTICASONE AND SALMETEROL

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

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ClinicalTrials.gov Identifier: NCT01709903
Recruitment Status : Completed
First Posted : October 18, 2012
Results First Posted : March 17, 2015
Last Update Posted : March 17, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease
Interventions Drug: QVA149
Drug: Fluticasone/salmeterol
Drug: Placebo to QVA149
Drug: Placebo to fluticasone/salmeterol
Enrollment 744
Recruitment Details Patients were randomized into 2 treatment arms of the study with an equal 1:1 randomization ratio: QVA149 and Flut/Salm
Pre-assignment Details A total of 1189 patients were screened; 744 (62.6%) completed the screening phase while 445 (37.4%) patients discontinued prior to completion of the screening phase
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description 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 Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Period Title: Overall Study
Started 372 [1] 372 [1]
Completed 343 333
Not Completed 29 39
Reason Not Completed
administrative problems             2             6
Abnormal test procedure results             1             0
In ability to use device             1             1
no longer needed study drug             0             1
Lost to Follow-up             0             2
Death             2             0
Protocol Violation             3             2
Lack of Efficacy             3             3
Withdrawal by Subject             6             6
Adverse Event             11             18
[1]
Randomized set
Arm/Group Title QVA149 Fluticasone/Salmeterol Total
Hide Arm/Group Description 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 Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device Total of all reporting groups
Overall Number of Baseline Participants 372 369 741
Hide Baseline Analysis Population Description
Three patients in the Flut/Salm treatment arm: were excluded from the FAS, safety set and PPS as they were randomized in error and did not receive the study medication.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 372 participants 369 participants 741 participants
64.8  (7.82) 65.3  (7.91) 65.0  (7.87)
[1]
Measure Description: Safety Set
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 372 participants 369 participants 741 participants
Female
31
   8.3%
38
  10.3%
69
   9.3%
Male
341
  91.7%
331
  89.7%
672
  90.7%
[1]
Measure Description: Safety Set
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 372 participants 369 participants 741 participants
American Indian or Alaska Native
1
   0.3%
2
   0.5%
3
   0.4%
Asian
314
  84.4%
309
  83.7%
623
  84.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
55
  14.8%
58
  15.7%
113
  15.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
2
   0.5%
0
   0.0%
2
   0.3%
[1]
Measure Description: Safety Set
1.Primary Outcome
Title Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
Hide Description Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.
Time Frame 26 weeks
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FAS
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description:
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
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Overall Number of Participants Analyzed 372 369
Least Squares Mean (Standard Error)
Unit of Measure: liters
1.248  (0.0173) 1.176  (0.0172)
2.Secondary Outcome
Title Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
Hide Description [Not Specified]
Time Frame 26 weeks
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FAS
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description:
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
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Overall Number of Participants Analyzed 372 369
Least Squares Mean (Standard Error)
Unit of Measure: liters
1.259  (.0170) 1.183  (0.0168)
3.Secondary Outcome
Title Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours
Hide Description 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.
Time Frame Day 1, 12 and 26 weeks
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Full Analysis set
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description:
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
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Overall Number of Participants Analyzed 372 369
Mean (Standard Deviation)
Unit of Measure: Liter
Day 1 (n=369,364) 1.317  (0.0096) 1.252  (0.0094)
12 weeks (n=350,338) 1.388  (0.0163) 1.262  (0.0161)
26 weeks (n=339,323) 1.351  (0.0167) 1.229  (0.0167)
4.Secondary Outcome
Title Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period
Hide Description Average of Trough Forced Expiratory Volume in one second (FEV1)
Time Frame 6,12,18 and 26 weeks
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Full analysis set
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description:
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
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Overall Number of Participants Analyzed 372 369
Least Squares Mean (Standard Error)
Unit of Measure: liter
Week 6 (n=356,341) 1.256  (0.0151) 1.184  (0.0149)
week 12 (n=346,333) 1.265  (0.0158) 1.191  (0.0156)
week 18 (n=339,332) 1.252  (0.0166) 1.174  (0.0164)
week 26 (n=338,324) 1.226  (0.0171) 1.142  (0.0171)
5.Secondary Outcome
Title Analysis of Trough FVC (L) Over the Whole Treatment Period
Hide Description Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose
Time Frame 12 and 26 weeks
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Full Analysis Set
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description:
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
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Overall Number of Participants Analyzed 372 369
Least Squares Mean (Standard Error)
Unit of Measure: liter
Day 1 (n=350,351) 3.040  (0.0288) 2.957  (0.0280)
Week 12 (n=342,332) 3.036  (0.0304) 2.835  (0.0302)
week 26 (n= 333,323) 2.966  (0.0334) 2.793  (0.0333)
6.Secondary Outcome
Title Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment
Hide Description A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.
Time Frame 26 weeks
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Full Analysis set
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description:
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
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Overall Number of Participants Analyzed 372 369
Mean (Standard Error)
Unit of Measure: numbers on a scale
Week 26 (n= 340,329) 31.20  (1.118) 32.00  (1.118)
Week 26 LOCF(n=354,342) 31.74  (1.136) 32.43  (1.130)
7.Secondary Outcome
Title Analysis of the TDI Focal Score Over the Whole Treatment Period
Hide Description The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. ."Baseline 12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point.
Time Frame 12 and 26 weeks
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Full Analysis Set
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description:
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
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Overall Number of Participants Analyzed 372 369
Least Squares Mean (Standard Error)
Unit of Measure: Numbers on a scale
Baseline 12 weeks (n=348,337) 6.36  (0.096) 6.36  (0.104)
12 weeks (n=348,337) 2.62  (0.240) 2.40  (0.238)
Baseline 26 weeks (n=335,326) 6.38  (0.097) 6.40  (0.105)
26 weeks (n=335,326) 3.02  (0.266) 2.86  (0.266)
8.Secondary Outcome
Title Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals
Hide Description 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. "Baseline 12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point. Less puffs taken is better.
Time Frame 12 and 26 weeks
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Full Analysis set
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description:
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
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Overall Number of Participants Analyzed 372 369
Mean (Standard Deviation)
Unit of Measure: # of puffs
Baseline Daytime 12-16 weeks (n=329,318) 1.57  (1.934) 1.69  (2.130)
Daytime 12-16 weeks (n=329,318) 0.66  (1.185) 0.61  (1.117)
Baseline Nighttime 12-16 weeks (n=322,307) 1.25  (1.5954) 1.24  (1.707)
Nighttime 12-16 weeks (n=322,307) 0.52  (1.007) 0.49  (0.960)
Baseline Daytime 24-26 weeks (n=326,315) 1.54  (1.885) 1.70  (2.160)
Daytime 24-26 weeks (n=326,315) 0.63  (1.226) 0.62  (1.135)
Baseline Night time 24-26 weeks (n=320,304) 1.23  (1.588) 1.21  (1.702)
Night time 24-26 weeks (n=320,304) 0.52  (1.087) 0.48  (0.923)
9.Secondary Outcome
Title Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment
Hide Description Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS)
Time Frame 26 weeks
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Full Analysis Set
Arm/Group Title QVA149 Fluticasone/Salmeterol
Hide Arm/Group Description:
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
Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
Overall Number of Participants Analyzed 372 369
Least Squares Mean (Standard Error)
Unit of Measure: % days in study
% nights ‘no nighttime awakenings' (n=336,322) 67.57  (2.138) 67.86  (2.101)
% days with ‘no daytime symptoms' (n=341,334) 7.31  (1.466) 10.22  (1.425)
% days able perform daily activities (n=341,334) 44.02  (2.200) 42.16  (2.140)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title QVA149 110mcg/50mcg Salmeterol/Fluticasone 50mcg/500mcg
Hide Arm/Group Description 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 Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
All-Cause Mortality
QVA149 110mcg/50mcg Salmeterol/Fluticasone 50mcg/500mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
QVA149 110mcg/50mcg Salmeterol/Fluticasone 50mcg/500mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   20/372 (5.38%)   35/369 (9.49%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  0/372 (0.00%)  1/369 (0.27%) 
Cardiac disorders     
Acute myocardial infarction  1  1/372 (0.27%)  0/369 (0.00%) 
Angina pectoris  1  0/372 (0.00%)  1/369 (0.27%) 
Arteriosclerosis coronary artery  1  0/372 (0.00%)  1/369 (0.27%) 
Atrial fibrillation  1  0/372 (0.00%)  1/369 (0.27%) 
Cardiac arrest  1  0/372 (0.00%)  1/369 (0.27%) 
Cardiac failure  1  0/372 (0.00%)  1/369 (0.27%) 
Cardiac failure congestive  1  1/372 (0.27%)  0/369 (0.00%) 
Cardio-respiratory arrest  1  0/372 (0.00%)  1/369 (0.27%) 
Cor pulmonale  1  1/372 (0.27%)  0/369 (0.00%) 
Cor pulmonale chronic  1  0/372 (0.00%)  1/369 (0.27%) 
Coronary artery disease  1  0/372 (0.00%)  1/369 (0.27%) 
Right ventricular dysfunction  1  1/372 (0.27%)  0/369 (0.00%) 
Eye disorders     
Conjunctivitis  1  0/372 (0.00%)  1/369 (0.27%) 
Pterygium  1  1/372 (0.27%)  0/369 (0.00%) 
Gastrointestinal disorders     
Inguinal hernia  1  0/372 (0.00%)  1/369 (0.27%) 
Large intestine polyp  1  0/372 (0.00%)  2/369 (0.54%) 
Upper gastrointestinal haemorrhage  1  1/372 (0.27%)  0/369 (0.00%) 
General disorders     
Hyperplasia  1  0/372 (0.00%)  1/369 (0.27%) 
Sudden cardiac death  1  1/372 (0.27%)  0/369 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  0/372 (0.00%)  1/369 (0.27%) 
Cholelithiasis  1  0/372 (0.00%)  1/369 (0.27%) 
Hepatic failure  1  0/372 (0.00%)  1/369 (0.27%) 
Hepatic function abnormal  1  0/372 (0.00%)  2/369 (0.54%) 
Infections and infestations     
Bronchitis  1  0/372 (0.00%)  1/369 (0.27%) 
Gastroenteritis  1  0/372 (0.00%)  1/369 (0.27%) 
Lung infection  1  1/372 (0.27%)  2/369 (0.54%) 
Pneumonia  1  2/372 (0.54%)  4/369 (1.08%) 
Septic shock  1  0/372 (0.00%)  2/369 (0.54%) 
Upper respiratory tract infection bacterial  1  0/372 (0.00%)  1/369 (0.27%) 
Injury, poisoning and procedural complications     
Laceration  1  0/372 (0.00%)  1/369 (0.27%) 
Metabolism and nutrition disorders     
Hyponatraemia  1  0/372 (0.00%)  1/369 (0.27%) 
Type 2 diabetes mellitus  1  1/372 (0.27%)  0/369 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Breast cancer  1  0/372 (0.00%)  1/369 (0.27%) 
Gastric cancer  1  1/372 (0.27%)  0/369 (0.00%) 
Lung neoplasm malignant  1  0/372 (0.00%)  1/369 (0.27%) 
Rectal cancer  1  1/372 (0.27%)  0/369 (0.00%) 
Nervous system disorders     
Cerebral infarction  1  2/372 (0.54%)  1/369 (0.27%) 
Vertebrobasilar insufficiency  1  0/372 (0.00%)  1/369 (0.27%) 
Renal and urinary disorders     
Renal failure  1  0/372 (0.00%)  2/369 (0.54%) 
Respiratory, thoracic and mediastinal disorders     
Atelectasis  1  1/372 (0.27%)  0/369 (0.00%) 
Chronic obstructive pulmonary disease  1  6/372 (1.61%)  17/369 (4.61%) 
Lung cyst  1  0/372 (0.00%)  1/369 (0.27%) 
Pneumothorax  1  0/372 (0.00%)  1/369 (0.27%) 
Pneumothorax spontaneous  1  1/372 (0.27%)  0/369 (0.00%) 
Respiratory failure  1  0/372 (0.00%)  2/369 (0.54%) 
Vascular disorders     
Aortic aneurysm  1  1/372 (0.27%)  0/369 (0.00%) 
Hypotension  1  0/372 (0.00%)  1/369 (0.27%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
QVA149 110mcg/50mcg Salmeterol/Fluticasone 50mcg/500mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   107/372 (28.76%)   135/369 (36.59%) 
Gastrointestinal disorders     
Gastritis  1  0/372 (0.00%)  4/369 (1.08%) 
General disorders     
Pyrexia  1  3/372 (0.81%)  5/369 (1.36%) 
Infections and infestations     
Bronchitis  1  7/372 (1.88%)  3/369 (0.81%) 
Nasopharyngitis  1  30/372 (8.06%)  45/369 (12.20%) 
Pneumonia  1  1/372 (0.27%)  6/369 (1.63%) 
Upper respiratory tract infection  1  13/372 (3.49%)  26/369 (7.05%) 
Upper respiratory tract infection bacterial  1  5/372 (1.34%)  3/369 (0.81%) 
Viral upper respiratory tract infection  1  1/372 (0.27%)  5/369 (1.36%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  69/372 (18.55%)  83/369 (22.49%) 
Dyspnoea  1  2/372 (0.54%)  6/369 (1.63%) 
Oropharyngeal pain  1  2/372 (0.54%)  6/369 (1.63%) 
Vascular disorders     
Hypertension  1  3/372 (0.81%)  5/369 (1.36%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01709903     History of Changes
Other Study ID Numbers: CQVA149A2331
First Submitted: October 16, 2012
First Posted: October 18, 2012
Results First Submitted: February 27, 2015
Results First Posted: March 17, 2015
Last Update Posted: March 17, 2015