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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 )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease
Interventions Drug: QVA149
Drug: Umeclidinium/vilanterol
Drug: Placebo (umeclidinium/vilanterol)
Drug: Placebo (QVA149)
Enrollment 357
Recruitment Details  
Pre-assignment Details Participants were randomized to 1 of 2 sequences in a 1:1 ratio.
Arm/Group Title First QVA149, Then Umeclidinium/Vilanterol First Umeclidinium/Vilanterol, Then QVA149
Hide Arm/Group Description 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. 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.
Period Title: Period 1
Started 178 179
Completed 165 171
Not Completed 13 8
Reason Not Completed
Physician Decision             0             1
Lack of Efficacy             1             0
Protocol deviation             3             2
Lost to Follow-up             2             0
Withdrawal by Subject             2             0
Adverse Event             5             5
Period Title: Washout
Started 165 171
Completed 162 163
Not Completed 3 8
Reason Not Completed
Lost to Follow-up             0             2
Withdrawal by Subject             1             4
Adverse Event             2             2
Period Title: Period 2
Started 162 163
Completed 154 158
Not Completed 8 5
Reason Not Completed
Protocol deviation             0             1
Lost to Follow-up             1             1
Withdrawal by Subject             1             1
Adverse Event             6             2
Arm/Group Title Overall Participants
Hide Arm/Group Description Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks and Umeclidinium/vilanterol 62.5/25 ug via inhalation once daily for 12 weeks.
Overall Number of Baseline Participants 357
Hide Baseline Analysis Population Description
Since this is a cross-over design study, all participants were randomized to receive both treatments, either in sequence QVA/UV or sequence UV/QVA. Therefore, the baseline characteristics are reported as overall participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 357 participants
64.1  (8.21)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 357 participants
Female
171
  47.9%
Male
186
  52.1%
1.Primary Outcome
Title Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h
Hide Description 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.
Time Frame baseline, 0 to 24 hours post-dose at week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and the post-baseline time point were included in the analysis.
Arm/Group Title QVA149 Umeclidinium/Vilanterol
Hide Arm/Group Description:
Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks.
Overall Number of Participants Analyzed 315 319
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.2321  (0.01133) 0.2436  (0.01130)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Umeclidinium/Vilanterol
Comments Ho: QVA149 27.5/12.5 μg b.i.d. is inferior to umeclidinium/vilanterol 62.5/25 μg q.d; Ha: QVA149 27.5/12.5 μg b.i.d. is non-inferior to umeclidinium/vilanterol 62.5/25 μg q.d.
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was demonstrated if the lower limit (LL) of the 97.5% one -sided confidence interval (CI) > -20 mL.
Statistical Test of Hypothesis P-Value 0.139
Comments p-value unadjusted
Method Linear Mixed Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0115
Confidence Interval (2-Sided) 95%
-0.0269 to 0.0038
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.00778
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Forced Expiratory Volume (FEV1) Area Under the Curve (AUC) 0-24h
Hide Description 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.
Time Frame baseline, 0 to 24 hours post-dose at week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and post-baseline time point were included in the analysis.
Arm/Group Title QVA149 Umeclidinium/Vilanterol
Hide Arm/Group Description:
Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks.
Overall Number of Participants Analyzed 315 319
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.2321  (0.01133) 0.2436  (0.01130)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Umeclidinium/Vilanterol
Comments Ho: QVA149 27.5/12.5 μg b.i.d. is inferior to umeclidinium/vilanterol 62.5/25 μg q.d; Ha: QVA149 27.5/12.5 μg b.i.d. is non-inferior to umeclidinium/vilanterol 62.5/25 μg q.d.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0115
Confidence Interval (2-Sided) 95%
-0.0269 to 0.0038
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.00778
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Trough FEV1 (Mean of 23h 15 Minutes and 23 h 45 Minutes Post Previous Morning Dose)
Hide Description 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
Time Frame baseline, 23 hours 15 minutes and 23 hours 45 minutes post previous morning dose at week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and the post-baseline time point were included in the analysis.
Arm/Group Title QVA149 Umeclidinium/Vilanterol
Hide Arm/Group Description:
Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks.
Overall Number of Participants Analyzed 309 310
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.1891  (0.01070) 0.2043  (0.01069)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Umeclidinium/Vilanterol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.0153
Confidence Interval (2-Sided) 95%
-0.0361 to 0.0056
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.01062
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in FEV1 AUC 12-24h
Hide Description 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).
Time Frame baseline, 12 hours to 24 hours post-dose at week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and the post-baseline time point were included in the analysis.
Arm/Group Title QVA149 Umeclidinium/Vilanterol
Hide Arm/Group Description:
Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks.
Overall Number of Participants Analyzed 312 316
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.2076  (0.01159) 0.2025  (0.01156)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection QVA149, Umeclidinium/Vilanterol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0051
Confidence Interval (2-Sided) 95%
-0.0108 to 0.0209
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.00806
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in FEV1 AUC 0-12h
Hide Description 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).
Time Frame baseline, 0 to 12 hours post-dose at week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and the post-baseline time point were included in the analysis.
Arm/Group Title QVA149 Umeclidinium/Vilanterol
Hide Arm/Group Description:
Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks.
Overall Number of Participants Analyzed 313 319
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.2543  (0.01031) 0.2848  (0.01026)
6.Secondary Outcome
Title Change From Baseline in FEV1 AUC 0-4h, AUC 4-8h, AUC 8-12h, AUC 12-16h, AUC 16-20h and AUC 20-24h
Hide Description 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.
Time Frame baseline, 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and the post-baseline time points were included in the analysis.
Arm/Group Title QVA149 Umeclidinium/Vilanterol
Hide Arm/Group Description:
Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks.
Overall Number of Participants Analyzed 341 340
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0-4h Number Analyzed 312 participants 319 participants
0.3223  (0.01087) 0.3289  (0.01080)
4-8h Number Analyzed 311 participants 317 participants
0.2399  (0.01051) 0.2831  (0.01045)
8-12h Number Analyzed 308 participants 315 participants
0.1911  (0.01069) 0.2411  (0.01062)
12-16h Number Analyzed 309 participants 315 participants
0.2594  (0.01241) 0.2349  (0.01236)
16-20h Number Analyzed 308 participants 312 participants
0.1914  (0.01247) 0.1875  (0.01244)
20-24h (n=310,314) Number Analyzed 310 participants 314 participants
0.1722  (0.01136) 0.1821  (0.01133)
7.Secondary Outcome
Title Change From Baseline in Pre-dose Trough FEV1 (Mean of 15 Minutes and 45 Minutes Pre Morning Dose)
Hide Description 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.
Time Frame baseline, 15 minutes and 45 minutes pre morning dose at week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and the post-baseline time point were included in the analysis.
Arm/Group Title QVA149 Umeclidinium/Vilanterol
Hide Arm/Group Description:
Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks.
Overall Number of Participants Analyzed 314 318
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.2302  (0.01138) 0.2450  (0.01135)
8.Secondary Outcome
Title QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in FEV1 at Any Time Point
Hide Description FEV1 was measured with spirometry conducted according to internationally accepted standards.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and the post-baseline time points were included in the analysis.
Arm/Group Title QVA149 Umeclidinium/Vilanterol
Hide Arm/Group Description:
Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks.
Overall Number of Participants Analyzed 341 340
Least Squares Mean (Standard Error)
Unit of Measure: Liter
Day 1, 5 minutes Number Analyzed 322 participants 326 participants
0.1112  (0.01011) 0.1201  (0.01007)
Day 1, 15 minutes Number Analyzed 320 participants 319 participants
0.1509  (0.01046) 0.1682  (0.01048)
Day 1, 30 minutes Number Analyzed 329 participants 329 participants
0.1602  (0.01071) 0.1945  (0.01073)
Day 1, 1 hour Number Analyzed 325 participants 331 participants
0.1755  (0.01105) 0.2230  (0.01100)
Day 1, 2 hours Number Analyzed 326 participants 331 participants
0.1840  (0.01161) 0.2329  (0.01157)
Day 1, 4 hours Number Analyzed 328 participants 330 participants
0.1432  (0.01107) 0.2270  (0.01105)
Day 1, 8 hours Number Analyzed 326 participants 325 participants
0.0815  (0.01054) 0.1861  (0.01056)
Day 1, 11 hours 55 minutes Number Analyzed 304 participants 318 participants
0.0699  (0.01153) 0.1674  (0.01138)
Day 1, 23 hours 15 minutes Number Analyzed 312 participants 326 participants
0.1498  (0.01078) 0.1764  (0.01063)
Day 1, 23 hours 45 minutes Number Analyzed 315 participants 328 participants
0.1579  (0.01103) 0.1932  (0.01090)
Week 6, -45 minutes Number Analyzed 317 participants 319 participants
0.2122  (0.01143) 0.2469  (0.01141)
Week 6, -15 minutes Number Analyzed 311 participants 314 participants
0.2378  (0.01181) 0.2668  (0.01179)
Week 12, -45 minutes Number Analyzed 311 participants 314 participants
0.2225  (0.01149) 0.2378  (0.01146)
Week 12, -15 minutes Number Analyzed 311 participants 314 participants
0.2390  (0.01182) 0.2538  (0.01179)
Week 12, 5 minutes Number Analyzed 308 participants 310 participants
0.2879  (0.01029) 0.2831  (0.01027)
Week 12, 15 minutes Number Analyzed 294 participants 298 participants
0.3187  (0.01079) 0.3074  (0.01074)
Week 12, 30 minutes Number Analyzed 301 participants 312 participants
0.3346  (0.01103) 0.3258  (0.01091)
Week 12, 1 hour Number Analyzed 304 participants 313 participants
0.3426  (0.01128) 0.3334  (0.01119)
Week 12, 2 hours Number Analyzed 303 participants 314 participants
0.3343  (0.01188) 0.3445  (0.01175)
Week 12, 4 hours Number Analyzed 302 participants 312 participants
0.2760  (0.01137) 0.3137  (0.01126)
Week 12, 8 hours Number Analyzed 304 participants 311 participants
0.2033  (0.01078) 0.2545  (0.01071)
Week 12, 11 hours 55 minutes Number Analyzed 276 participants 307 participants
0.1764  (0.01189) 0.2311  (0.01151)
Week 12, 12 hours 5 minutes Number Analyzed 294 participants 305 participants
0.2343  (0.01257) 0.2218  (0.01242)
Week 12, 12 hours 15 minutes Number Analyzed 296 participants 304 participants
0.2465  (0.01291) 0.2324  (0.01282)
Week 12, 12 hours 30 minutes Number Analyzed 296 participants 300 participants
0.2695  (0.01307) 0.2350  (0.01302)
Week 12, 13 hours Number Analyzed 292 participants 301 participants
0.2749  (0.01305) 0.2448  (0.01294)
Week 12, 14 hours Number Analyzed 290 participants 306 participants
0.2667  (0.01331) 0.2355  (0.01314)
Week 12, 16 hours Number Analyzed 290 participants 298 participants
0.2230  (0.01306) 0.2197  (0.01296)
Week 12, 20 hours Number Analyzed 291 participants 298 participants
0.1622  (0.01281) 0.1629  (0.01273)
Week 12, 23 hours 15 minutes (n=299,305) Number Analyzed 299 participants 305 participants
0.1791  (0.01095) 0.1981  (0.01088)
Week 12, 23 hours 45 minutes Number Analyzed 300 participants 303 participants
0.2048  (0.01122) 0.2117  (0.01118)
9.Secondary Outcome
Title QVA149 Compared to Umeclidinium/Vilanterol in Terms of Change From Baseline in Forced Vital Capacity (FVC) at Any Time Point
Hide Description FEV1 was measured with spirometry conducted according to internationally accepted standards.
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)
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis, which included all randomized patients who received at least one dose of double-blind treatment, was considered for the analysis. Only participants with a value at both baseline and the post-baseline time points were included in the analysis.
Arm/Group Title QVA149 Umeclidinium/Vilanterol
Hide Arm/Group Description:
Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks.
Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks.
Overall Number of Participants Analyzed 341 340
Least Squares Mean (Standard Error)
Unit of Measure: Liter
Day 1, 5 minutes Number Analyzed 322 participants 326 participants
0.2177  (0.01732) 0.2218  (0.01726)
Day 1, 15 minutes Number Analyzed 320 participants 319 participants
0.2566  (0.01818) 0.2927  (0.01821)
Day 1, 30 minutes Number Analyzed 329 participants 329 participants
0.2811  (0.01846) 0.3325  (0.01849)
Day 1, 1 hour Number Analyzed 325 participants 331 participants
0.2944  (0.01912) 0.3534  (0.01904)
Day 1, 2 hours Number Analyzed 326 participants 331 participants
0.3109  (0.01966) 0.3687  (0.01960)
Day 1, 4 hours Number Analyzed 328 participants 330 participants
0.2788  (0.04347) 0.4237  (0.04339)
Day 1, 8 hours Number Analyzed 326 participants 325 participants
0.1681  (0.01816) 0.3237  (0.01818)
Day 1, 11 hours 55 minutes Number Analyzed 304 participants 318 participants
0.1406  (0.01915) 0.2910  (0.01889)
Day 1, 23 hours 15 minutes Number Analyzed 312 participants 326 participants
0.2565  (0.01777) 0.2747  (0.01753)
Day 1, 23 hours 45 minutes Number Analyzed 315 participants 328 participants
0.2737  (0.01903) 0.3001  (0.01883)
Week 6, -45 minutes Number Analyzed 317 participants 319 participants
0.2914  (0.01853) 0.3513  (0.01851)
Week 6, -15 minutes Number Analyzed 311 participants 314 participants
0.3390  (0.01922) 0.3732  (0.01919)
Week 12, -45 minutes Number Analyzed 311 participants 314 participants
0.3044  (0.01864) 0.3442  (0.01859)
Week 12, -15 minutes Number Analyzed 311 participants 314 participants
0.3344  (0.01923) 0.3566  (0.01919)
Week 12, 5 minutes Number Analyzed 308 participants 310 participants
0.3960  (0.01760) 0.3861  (0.01756)
Week 12, 15 minutes Number Analyzed 294 participants 298 participants
0.4378  (0.01865) 0.4169  (0.01857)
Week 12, 30 minutes Number Analyzed 301 participants 312 participants
0.4602  (0.01892) 0.4480  (0.01875)
Week 12, 1 hour Number Analyzed 304 participants 313 participants
0.4649  (0.01948) 0.4647  (0.01934)
Week 12, 2 hours Number Analyzed 303 participants 314 participants
0.4405  (0.02006) 0.4853  (0.01987)
Week 12, 4 hours Number Analyzed 302 participants 312 participants
0.3872  (0.04490) 0.4343  (0.04435)
Week 12, 8 hours Number Analyzed 304 participants 311 participants
0.2714  (0.01856) 0.3555  (0.01844)
Week 12, 11 hours 55 minutes Number Analyzed 276 participants 307 participants
0.2306  (0.01977) 0.3231  (0.01911)
Week 12, 12 hours 5 minutes (n=294,305) Number Analyzed 294 participants 305 participants
0.3455  (0.02063) 0.3112  (0.02038)
Week 12, 12 hours 15 minutes Number Analyzed 296 participants 304 participants
0.3409  (0.02086) 0.3235  (0.02070)
Week 12, 12 hours 30 minutes Number Analyzed 296 participants 300 participants
0.3688  (0.02196) 0.3326  (0.02187)
Week 12, 13 hours Number Analyzed 292 participants 301 participants
0.3760  (0.02123) 0.3361  (0.02104)
Week 12, 14 hours Number Analyzed 290 participants 306 participants
0.3681  (0.02192) 0.3371  (0.02162)
Week 12, 16 hours Number Analyzed 290 participants 298 participants
0.3129  (0.02205) 0.3279  (0.02189)
Week 12, 20 hours Number Analyzed 291 participants 298 participants
0.2175  (0.02180) 0.2353  (0.02167)
Week 12, 23 hours 15 minutes Number Analyzed 299 participants 305 participants
0.2237  (0.01804) 0.2750  (0.01792)
Week 12, 23 hours 45 minutes (n=300,303) Number Analyzed 300 participants 303 participants
0.2607  (0.01935) 0.2728  (0.01928)
Time Frame [Not Specified]
Adverse Event Reporting Description Since this is a cross-over design study, all patients were randomized to receive both treatments, either in sequence QVA/UV or sequence UV/QVA. The number of patients on each treatment does not add up to the total number of patients.
 
Arm/Group Title QVA149 Umeclidinium/Vilanterol All Patients
Hide Arm/Group Description Participants received QVA149 27.5/12.5 ug via inhalation twice daily (b.i.d.) for 12 weeks. Participants received Umeclidinium/vilanterol 62.5/25 ug via inhalation b.i.d. for 12 weeks. All Patients
All-Cause Mortality
QVA149 Umeclidinium/Vilanterol All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
QVA149 Umeclidinium/Vilanterol All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/341 (3.81%)   21/340 (6.18%)   33/356 (9.27%) 
Blood and lymphatic system disorders       
Anaemia † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Neutropenia † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Thrombocytopenia † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Cardiac disorders       
Acute myocardial infarction † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Cardiac failure congestive † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Coronary artery disease † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Mitral valve incompetence † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Ventricular extrasystoles † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Gastrointestinal disorders       
Large intestinal haemorrhage † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Small intestinal obstruction † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Hepatobiliary disorders       
Cholecystitis † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Infections and infestations       
Appendicitis † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Bacteraemia † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Bronchitis † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Escherichia bacteraemia † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Pharyngitis † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Pneumonia † 1  1/341 (0.29%)  5/340 (1.47%)  6/356 (1.69%) 
Urinary tract infection † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Injury, poisoning and procedural complications       
Muscle strain † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Metabolism and nutrition disorders       
Type 2 diabetes mellitus † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acute myeloid leukaemia † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Basal cell carcinoma † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Lung neoplasm malignant † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Squamous cell carcinoma † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Psychiatric disorders       
Major depression † 1  0/341 (0.00%)  1/340 (0.29%)  1/356 (0.28%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure † 1  3/341 (0.88%)  2/340 (0.59%)  5/356 (1.40%) 
Chronic obstructive pulmonary disease † 1  7/341 (2.05%)  6/340 (1.76%)  13/356 (3.65%) 
Hypoxia † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
Respiratory failure † 1  2/341 (0.59%)  0/340 (0.00%)  2/356 (0.56%) 
Vascular disorders       
Deep vein thrombosis † 1  1/341 (0.29%)  0/340 (0.00%)  1/356 (0.28%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
QVA149 Umeclidinium/Vilanterol All Patients
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   85/341 (24.93%)   104/340 (30.59%)   161/356 (45.22%) 
Blood and lymphatic system disorders       
Anaemia † 1  1/341 (0.29%)  3/340 (0.88%)  4/356 (1.12%) 
Gastrointestinal disorders       
Diarrhoea † 1  1/341 (0.29%)  3/340 (0.88%)  4/356 (1.12%) 
Nausea † 1  3/341 (0.88%)  1/340 (0.29%)  4/356 (1.12%) 
Vomiting † 1  1/341 (0.29%)  3/340 (0.88%)  4/356 (1.12%) 
General disorders       
Fatigue † 1  2/341 (0.59%)  2/340 (0.59%)  4/356 (1.12%) 
Infections and infestations       
Bronchitis † 1  5/341 (1.47%)  11/340 (3.24%)  15/356 (4.21%) 
Lower respiratory tract infection † 1  3/341 (0.88%)  3/340 (0.88%)  6/356 (1.69%) 
Nasopharyngitis † 1  19/341 (5.57%)  12/340 (3.53%)  28/356 (7.87%) 
Sinusitis † 1  4/341 (1.17%)  2/340 (0.59%)  5/356 (1.40%) 
Upper respiratory tract infection † 1  6/341 (1.76%)  11/340 (3.24%)  16/356 (4.49%) 
Upper respiratory tract infection bacterial † 1  1/341 (0.29%)  3/340 (0.88%)  4/356 (1.12%) 
Urinary tract infection † 1  1/341 (0.29%)  4/340 (1.18%)  5/356 (1.40%) 
Viral upper respiratory tract infection † 1  4/341 (1.17%)  6/340 (1.76%)  10/356 (2.81%) 
Metabolism and nutrition disorders       
Hyponatraemia † 1  3/341 (0.88%)  1/340 (0.29%)  4/356 (1.12%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  3/341 (0.88%)  4/340 (1.18%)  7/356 (1.97%) 
Back pain † 1  0/341 (0.00%)  4/340 (1.18%)  4/356 (1.12%) 
Nervous system disorders       
Headache † 1  3/341 (0.88%)  5/340 (1.47%)  8/356 (2.25%) 
Psychiatric disorders       
Anxiety † 1  2/341 (0.59%)  3/340 (0.88%)  5/356 (1.40%) 
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease † 1  36/341 (10.56%)  50/340 (14.71%)  76/356 (21.35%) 
Cough † 1  6/341 (1.76%)  5/340 (1.47%)  10/356 (2.81%) 
Dyspnoea † 1  7/341 (2.05%)  8/340 (2.35%)  14/356 (3.93%) 
Nasal congestion † 1  2/341 (0.59%)  3/340 (0.88%)  5/356 (1.40%) 
Oropharyngeal pain † 1  10/341 (2.93%)  5/340 (1.47%)  14/356 (3.93%) 
Rhinorrhoea † 1  3/341 (0.88%)  1/340 (0.29%)  4/356 (1.12%) 
Vascular disorders       
Hypertension † 1  3/341 (0.88%)  3/340 (0.88%)  6/356 (1.69%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.1)
[Not Specified]
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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-1873
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02487446    
Other Study ID Numbers: CQVA149A2349
First Submitted: June 29, 2015
First Posted: July 1, 2015
Results First Submitted: September 12, 2017
Results First Posted: December 26, 2017
Last Update Posted: December 26, 2017