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Trial record 1 of 1 for:    CQVA149A2337
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A 12-week Treatment, Multi-center, Randomized, Double-blind, Parallel-group, Placebo and Active Controlled Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol Maleate / Glycopyrronium Bromide in COPD Patients With Moderate to Severe Airflow Limitation

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ClinicalTrials.gov Identifier: NCT01712516
Recruitment Status : Completed
First Posted : October 23, 2012
Results First Posted : July 15, 2015
Last Update Posted : July 15, 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 (COPD)
Interventions Drug: QVA149
Drug: QAB149
Drug: NVA237
Drug: Placebo
Enrollment 1001
Recruitment Details Participants were randomized to each treatment arm in a 1:1:1:1 ratio.
Pre-assignment Details One thousand one participants were randomized. (One participant was randomized twice, took study drug twice and was counted twice in the randomized and safety sets). In the safety set, participants were analyzed according to the treatment received.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description 27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI) 27.5 ug b.i.d. 12.5 ug b.i.d. b.i.d.
Period Title: Overall Study
Started 250 251 251 249
Safety Set 250 251 251 248
Full Analysis Set 250 251 250 247
Completed 244 241 245 236
Not Completed 6 10 6 13
Reason Not Completed
Technical problems             0             0             0             2
Lost to Follow-up             0             0             2             1
Death             0             1             0             0
Protocol deviation             1             0             1             0
Physician Decision             2             0             0             1
Withdrawal by Subject             3             9             3             9
Arm/Group Title QVA149 QAB149 NVA237 Placebo Total
Hide Arm/Group Description 27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI) 27.5 ug b.i.d. 12.5 ug b.i.d. b.i.d. Total of all reporting groups
Overall Number of Baseline Participants 250 251 251 249 1001
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 250 participants 251 participants 251 participants 249 participants 1001 participants
62.8  (8.46) 63.7  (8.58) 63.1  (8.53) 62.5  (8.07) 63.0  (8.41)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 250 participants 251 participants 251 participants 249 participants 1001 participants
Female
96
  38.4%
101
  40.2%
107
  42.6%
111
  44.6%
415
  41.5%
Male
154
  61.6%
150
  59.8%
144
  57.4%
138
  55.4%
586
  58.5%
1.Primary Outcome
Title Primary: Change From Baseline in Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) (0-12 Hours (h))
Hide Description Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction. Missing values of FEV1 AUC0-12 at Day 1 and Week 12 will not imputed. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time.
Time Frame baseline (BL), 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study treatment. Participants, who were missing day 1 and/or week 12 FEV1 AUC 0-12h measurements, were not included in the analysis.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 249 251 250 246
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.234  (0.0134) 0.122  (0.0134) 0.155  (0.0134) -0.028  (0.0137)
2.Secondary Outcome
Title Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score
Hide Description Participants reported change in health status by using the SGRQ. 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. Missing week 12 data were imputed with Last Observation Carried Forward (LOCF) method but only if measured at day >= 29. A negative change from baseline indicates improvement.
Time Frame BL, 12 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: The full analysis set included all randomized participants who received at least one dose of study treatment. Participants missing week 12 data were not included in the analysis.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 238 234 237 226
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-7.5  (0.85) -5.9  (0.86) -6.0  (0.86) -1.1  (0.88)
3.Secondary Outcome
Title Percentage of Participants With a Clinically Important Improvement of at Least 4 Units in the SGRQ Total Score
Hide Description Participants reported change in health status by using the SGRQ. 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.
Time Frame 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants from the full analysis set, who had a SGRQ total score, were included in the analysis. The full analysis set included all randomized participants who received at least one dose of study treatment.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 238 234 237 226
Measure Type: Number
Unit of Measure: Percentage of participants
59.2 56.8 51.5 34.5
4.Secondary Outcome
Title Change From Baseline in Trough FEV1
Hide Description Pulmonary function assessments were performed using centralized spirometry according to international standards. Trough FEV1 was analyzed using the same MMRM as specified for FEV1. Trough FEV1 was defined as the mean of FEV1 at 23 h 15 min and 23 h 45 min after the morning dose of the previous day. Before the mean was calculated, a time window of 10 – 13 hours post-evening dose was applied to these 2 measurements. Recordings outside the time window were set to missing.
Time Frame BL, day 2, day 86
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and post baseline values for a given time point, were included in the analysis for that time point.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 246 251 249 245
Least Squares Mean (Standard Error)
Unit of Measure: Liters
day 2 0.208  (0.0107) 0.111  (0.0106) 0.132  (0.0107) 0.010  (0.0107)
day 86 0.216  (0.0142) 0.138  (0.0141) 0.128  (0.0142) -0.017  (0.0145)
5.Secondary Outcome
Title Change From Baseline in Pre-dose Trough FEV1
Hide Description Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was analyzed using the same MMRM as specified for FEV1. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose. Since the time of evening dose of the previous day was not recorded at these visits, no time window was applied.
Time Frame BL, day 85
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and week 12 values, were included in the analysis.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 243 249 246 241
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.193  (0.0132) 0.100  (0.0132) 0.108  (0.0133) -0.027  (0.0135)
6.Secondary Outcome
Title Change From Baseline in FEV1
Hide Description Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.
Time Frame BL, Day 1: 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55 min; Day 2: 23h15min, 23h45min; Day 15: -45min, -15min, 1h; Day 29: -45 min, -15min, 1h; Day 57: -45min, -15min, 1h; day 85: -45min, -15min, 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h; day 86: 23h15min; 23h45min
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study medication. Participants, who has both baseline and post baseline values for a given time point, were included in the analysis for that time point.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 250 251 250 247
Least Squares Mean (Standard Error)
Unit of Measure: Liters
day 1, 5 min (n=248,249,249,243) 0.117  (0.0061) 0.076  (0.0060) 0.072  (0.0061) -0.001  (0.0062)
day 1, 15 min (n=248,251,249,244) 0.160  (0.0070) 0.090  (0.0069) 0.126  (0.0070) 0.005  (0.0070)
day 1, 1 h (n=249,251,249,246) 0.199  (0.0082) 0.089  (0.0082) 0.176  (0.0083) 0.008  (0.0083)
day 1, 2 h (n=249,249,248,246) 0.237  (0.0091) 0.109  (0.0091) 0.197  (0.0092) 0.030  (0.0092)
day 1, 4 h (n=247,247,248,237) 0.220  (0.0099) 0.108  (0.0099) 0.167  (0.0099) 0.019  (0.0101)
day 1, 6 h (n=247,246,244,239) 0.181  (0.0103) 0.085  (0.0104) 0.135  (0.0104) -0.005  (0.0106)
day 1, 8 h (n=248,247,245,242) 0.165  (0.0102) 0.077  (0.0101) 0.112  (0.0103) -0.019  (0.0104)
day 1, 11 h 55 min(n=242,243,244,239) 0.116  (0.0114) 0.029  (0.0114) 0.066  (0.0114) -0.045  (0.0115)
day 2, 23 h 15 min (n=241,246,245,241) 0.201  (0.0111) 0.105  (0.0110) 0.128  (0.0111) 0.002  (0.0111)
day 2, 23 h 45 min (n= 246,251,248,244) 0.216  (0.0111) 0.118  (0.0109) 0.137  (0.0111) 0.018  (0.0111)
day 15, - 45 min (243,249,246,240) 0.208  (0.0126) 0.114  (0.0124) 0.108  (0.0126) -0.045  (0.0127)
day 15, -15 min (n=243,248,246,241) 0.238  (0.0124) 0.143  (0.0123) 0.132  (0.0124) -0.025  (0.0124)
day 15, 1 h (n=249,251,249,246) 0.321  (0.0134) 0.179  (0.0133) 0.212  (0.0134) -0.019  (0.0135)
day 29, -45 min (n=243,249,246,240) 0.213  (0.0132) 0.127  (0.0131) 0.117  (0.0132) -0.030  (0.0133)
day 29, -15 min (n=243,248,246,241) 0.235  (0.0132) 0.147  (0.0131) 0.138  (0.0132) -0.013  (0.0134)
day 29, 1 h (n=249,251,249,246) 0.320  (0.0135) 0.170  (0.0135) 0.216  (0.0136) -0.004  (0.0137)
day 57, -45 min (n=243,249,246,240) 0.203  (0.0136) 0.104  (0.0136) 0.117  (0.0137) -0.037  (0.0140)
day 57, -15 min (n=243,248,246,241) 0.224  (0.0136) 0.125  (0.0135) 0.147  (0.0136) -0.014  (0.0139)
day 57, 1 h (n=249,251,249,246) 0.319  (0.0143) 0.163  (0.0143) 0.221  (0.0144) -0.016  (0.0146)
day 85, -45 min (n=243,249,246,240) 0.187  (0.0134) 0.090  (0.0135) 0.096  (0.0135) -0.032  (0.0138)
day 85, - 15 min (n=243,248,246,241) 0.199  (0.0138) 0.109  (0.0137) 0.123  (0.0138) -0.018  (0.0141)
day 85, 5 min (n=248,249,249,243) 0.246  (0.0142) 0.151  (0.0143) 0.143  (0.0142) -0.020  (0.0144)
day 85, 15 min (n=248,251,249,244) 0.269  (0.0141) 0.153  (0.0142) 0.179  (0.0141) -0.001  (0.0145)
day 85, 1 h (n=249,251,249,246) 0.293  (0.0144) 0.141  (0.0144) 0.208  (0.0144) -0.018  (0.0147)
day 85, 2 h (n=249,249,248,246) 0.315  (0.0146) 0.159  (0.0147) 0.216  (0.0148) -0.001  (0.0150)
day 85, 4 h (n=247,247,248,237) 0.260  (0.0150) 0.145  (0.0151) 0.172  (0.0151) -0.004  (0.0157)
day 85, 6 h (n=247,246,244,239) 0.226  (0.0149) 0.122  (0.0150) 0.139  (0.0151) -0.011  (0.0155)
day 85, 8 h (n=248,247,245,242) 0.198  (0.0146) 0.107  (0.0147) 0.133  (0.0149) -0.039  (0.0153)
day 85, 11 h 55 min(n=242,243,244,239) 0.163  (0.0147) 0.078  (0.0150) 0.105  (0.0150) -0.073  (0.0154)
day 86, 23 h 15 min (n=241,246,245,241) 0.206  (0.0148) 0.130  (0.0147) 0.117  (0.0149) -0.023  (0.0150)
day 86, 23 h 45 min (n=246,251,248,244) 0.221  (0.0144) 0.144  (0.0144) 0.132  (0.0146) -0.012  (0.0149)
7.Secondary Outcome
Title Change From Baseline in FVC
Hide Description Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FVC measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.
Time Frame BL, Day 1: 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h55 min; Day 2: 23h15min, 23h45min; Day 15: -45min, -15min, 1h; Day 29: -45 min, -15min, 1h; Day 57: -45min, -15min, 1h; day 85: -45min, -15min, 5min, 15min, 1h, 2h, 4h, 6h, 8h, 11h; day 86: 23h15min; 23h45min
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study medication. Participants, who has both baseline and post baseline values for a given time point, were included in the analysis for that time point.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 250 251 250 247
Least Squares Mean (Standard Error)
Unit of Measure: Liters
day 1, 5 min (n=248,249,249,243) 0.245  (0.0138) 0.175  (0.0136) 0.158  (0.0137) -0.006  (0.0140)
day 1, 15 min (n=248,251,249,244) 0.318  (0.0154) 0.185  (0.0153) 0.238  (0.0155) 0.009  (0.0155)
day 1, 1 h (n=249,251,249,246) 0.355  (0.0165) 0.153  (0.0164) 0.309  (0.0166) 0.013  (0.0166)
day 1, 2 h (n=249,249,248,246) 0.395  (0.0181) 0.214  (0.0180) 0.324  (0.0182) 0.044  (0.0183)
day 1, 4 h (n=247,247,248,237) 0.364  (0.0187) 0.189  (0.0187) 0.271  (0.0188) 0.026  (0.0192)
day 1, 6 h (n=247,246,244,239) 0.316  (0.0186) 0.159  (0.0188) 0.244  (0.0189) 0.004  (0.0192)
day 1, 8 h (n=248,247,245,242) 0.285  (0.0179) 0.154  (0.0178) 0.212  (0.0182) -0.021  (0.0183)
day 1, 11 h 55 min (n=242,243,244,239) 0.235  (0.0188) 0.093  (0.0188) 0.125  (0.0188) -0.060  (0.0190)
day 2, 23 h 15 min (n=241,246,245,241) 0.343  (0.0193) 0.191  (0.0191) 0.217  (0.0194) 0.001  (0.0194)
day 2, 23 h 45 min (n=246,251,248,244) 0.355  (0.0195) 0.196  (0.0192) 0.229  (0.0194) 0.027  (0.0195)
day 15, -45 min (n=243,249,246,240) 0.313  (0.0205) 0.163  (0.0201) 0.168  (0.0204) -0.047  (0.0206)
day 15, -15 min (n=243,248,246,241) 0.358  (0.0207) 0.201  (0.0204) 0.198  (0.0207) -0.020  (0.0207)
day 15, 1 h (n=249,251,249,246) 0.473  (0.0025) 0.269  (0.0223) 0.311  (0.0225) -0.009  (0.0227)
day 29, -45 min (n=243,249,246,240) 0.320  (0.0217) 0.194  (0.0216) 0.188  (0.0217) -0.025  (0.0220)
day 29, -15 min (n=243,248,246,241) 0.332  (0.0216) 0.218  (0.0215) 0.197  (0.0216) -0.004  (0.0219)
day 29, 1 h (n=249,251,249,246) 0.449  (0.0224) 0.259  (0.0223) 0.322  (0.0225) 0.008  (0.0227)
day 57, -45 min (n=243,249,246,240) 0.293  (0.0215) 0.142  (0.0215) 0.173  (0.0217) -0.034  (0.0221)
day 57, -15 min (n=243,248,246,241) 0.298  (0.0223) 0.167  (0.0222) 0.222  (0.0224) -0.009  (0.0229)
day 57, 1 h (n=249,251,249,246) 0.445  (0.0233) 0.227  (0.0233) 0.326  (0.0234) -0.011  (0.0238)
day 85, -45 min (n=243,249,246,240) 0.252  (0.0223) 0.121  (0.0224) 0.143  (0.0225) -0.029  (0.0229)
day 85, -15 min (n=243,248,246,241) 0.263  (0.0224) 0.142  (0.0223) 0.180  (0.0225) -0.031  (0.0229)
day 85, 5 min (n=248,249,249,243) 0.331  (0.0243) 0.215  (0.0244) 0.225  (0.0243) -0.048  (0.0247)
day 85, 15 min (n=248,251,249,244) 0.377  (0.0242) 0.223  (0.0243) 0.276  (0.0243) -0.004  (0.0248)
day 85, 1 h (n=249,251,249,246) 0.400  (0.0243) 0.209  (0.0243) 0.295  (0.0244) -0.023  (0.0248)
day 85, 2h (n=249,249,248,246) 0.414  (0.0244) 0.218  (0.0245) 0.301  (0.0247) -0.001  (0.0251)
day 85, 4 h (n=247,247,248,237) 0.338  (0.0247) 0.203  (0.0249) 0.261  (0.0250) 0.002  (0.0259)
day 85, 6 h (n=247,246,244,239) 0.305  (0.0239) 0.164  (0.0240) 0.211  (0.0241) -0.011  (0.0248)
day 85, 8 h (n=248,247,245,242) 0.273  (0.0233) 0.152  (0.0235) 0.213  (0.0237) -0.038  (0.0244)
day 85, 11 55 min (n=242,243,244,239) 0.233  (0.0239) 0.131  (0.0243) 0.197  (0.0243) -0.093  (0.0250)
day 86, 23 h 15 min (n=241,246,245,241) 0.278  (0.0248) 0.172  (0.0247) 0.176  (0.0250) -0.021  (0.0251)
day 86, 23 h 45 min (n=246,251,248,244) 0.298  (0.0240) 0.199  (0.0239) 0.210  (0.0244) -0.017  (0.0248)
8.Secondary Outcome
Title Secondary: Change From Baseline in Standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)
Hide Description Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time.
Time Frame BL, day 1, 12 weeks
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Hide Analysis Population Description
Full Analysis Set: The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and post baseline values for a given time point, were included in the analysis for that time point.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 250 251 250 247
Least Squares Mean (Standard Error)
Unit of Measure: Liters
Day 1, AUC 0-4h (n=249,251,250,246) 0.213  (0.0077) 0.101  (0.0077) 0.174  (0.0077) 0.019  (0.0078)
Day 1, AUC 4-8h (n=248,248,250,243) 0.187  (0.0093) 0.090  (0.0093) 0.134  (0.0093) -0.003  (0.0095)
Day 1, AUC 8-12h (n=248,249,249,245) 0.143  (0.0099) 0.054  (0.0099) 0.092  (0.0100) -0.031  (0.0101)
Day 1, AUC 0-12h (n=249,251,250,246) 0.184  (0.0084) 0.080  (0.0084) 0.135  (0.0084) -0.003  (0.0085)
Week 12, AUC 0-4h (n=249,251,250,246) 0.289  (0.0138) 0.147  (0.0138) 0.196  (0.0138) -0.008  (0.0141)
Week 12, AUC 4-8h (n=248,248,250,243) 0.229  (0.0140) 0.120  (0.0141) 0.148  (0.0141) -0.021  (0.0145)
Week 12, AUC 8-12h (n=248,249,249,245) 0.182  (0.0141) 0.095  (0.0142) 0.123  (0.0143) -0.055  (0.0146)
Week 12, AUC 0-12h (n=249,251,250,246) 0.234  (0.0134) 0.122  (0.0134) 0.155  (0.0134) -0.028  (0.0137)
9.Secondary Outcome
Title Transitional Dyspnea Index (TDI) Focal Score
Hide Description 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.
Time Frame BL, 12 weeks
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Hide Analysis Population Description
Full Analysis Set (FAS) The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and week 12 scores, were included in the analysis.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 233 238 232 222
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
2.88  (0.251) 1.98  (0.252) 1.88  (0.252) 0.85  (0.256)
10.Secondary Outcome
Title Secondary: Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
Hide Description Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours. A negative change from baseline indicates improvement.
Time Frame BL, 12 weeks
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Hide Analysis Population Description
Full Analysis Set (FAS) The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and week 12 values, were included in the analysis.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 243 242 242 235
Least Squares Mean (Standard Error)
Unit of Measure: number of puffs
-2.19  (0.150) -2.05  (0.150) -1.78  (0.151) -1.04  (0.153)
11.Secondary Outcome
Title Secondary: Change From Baseline in Mean Total Daily Symptom Score, Mean Daytime Total Symptom Score and Mean Nighttime Total Symptom Score
Hide Description The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.
Time Frame BL, 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) The FAS included all randomized participants who received at least one dose of study treatment. Participants, who had both baseline and week 12 values, were included in the analysis.
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description:
27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI)
27.5 ug b.i.d.
12.5 ug b.i.d.
b.i.d.
Overall Number of Participants Analyzed 250 251 250 247
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
total daily (n=243,242,242,235) -1.34  (0.108) -1.22  (0.108) -1.09  (0.108) -0.61  (0.110)
total daytime (n=242,239,240,234) -1.16  (0.105) -1.05  (0.105) -0.96  (0.105) -0.53  (0.106)
total nighttime (n=243,239,238,234) -1.09  (0.107) -1.01  (0.107) -0.90  (0.108) -0.41  (0.109)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title QVA149 QAB149 NVA237 Placebo
Hide Arm/Group Description 27.5/12.5 ug twice daily (b.i.d.) via Single Dose Dry Powder Inhaler (SDDPI) 27.5 ug b.i.d. 12.5 ug b.i.d. b.i.d.
All-Cause Mortality
QVA149 QAB149 NVA237 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
QVA149 QAB149 NVA237 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/250 (2.40%)   5/251 (1.99%)   12/251 (4.78%)   13/248 (5.24%) 
Blood and lymphatic system disorders         
ANAEMIA  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  1/248 (0.40%) 
Cardiac disorders         
ANGINA PECTORIS  1  0/250 (0.00%)  1/251 (0.40%)  0/251 (0.00%)  0/248 (0.00%) 
CARDIAC FAILURE  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  1/248 (0.40%) 
CARDIO-RESPIRATORY ARREST  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
CARDIOPULMONARY FAILURE  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
MYOCARDIAL INFARCTION  1  1/250 (0.40%)  0/251 (0.00%)  0/251 (0.00%)  0/248 (0.00%) 
Gastrointestinal disorders         
INGUINAL HERNIA  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
PNEUMOPERITONEUM  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
General disorders         
CHEST PAIN  1  1/250 (0.40%)  0/251 (0.00%)  0/251 (0.00%)  0/248 (0.00%) 
OEDEMA PERIPHERAL  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
Hepatobiliary disorders         
HEPATIC FUNCTION ABNORMAL  1  0/250 (0.00%)  1/251 (0.40%)  0/251 (0.00%)  0/248 (0.00%) 
Infections and infestations         
EPIGLOTTITIS  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
LOWER RESPIRATORY TRACT INFECTION  1  0/250 (0.00%)  1/251 (0.40%)  0/251 (0.00%)  0/248 (0.00%) 
PERIRECTAL ABSCESS  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
PNEUMONIA  1  1/250 (0.40%)  0/251 (0.00%)  0/251 (0.00%)  0/248 (0.00%) 
SINUSITIS  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  1/248 (0.40%) 
UPPER RESPIRATORY TRACT INFECTION BACTERIAL  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
Injury, poisoning and procedural complications         
FEMUR FRACTURE  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  1/248 (0.40%) 
GUN SHOT WOUND  1  0/250 (0.00%)  1/251 (0.40%)  0/251 (0.00%)  0/248 (0.00%) 
Investigations         
HEPATIC ENZYME INCREASED  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  1/248 (0.40%) 
Metabolism and nutrition disorders         
DEHYDRATION  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  1/248 (0.40%) 
Musculoskeletal and connective tissue disorders         
OSTEOARTHRITIS  1  0/250 (0.00%)  1/251 (0.40%)  0/251 (0.00%)  0/248 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
BASAL CELL CARCINOMA  1  1/250 (0.40%)  0/251 (0.00%)  0/251 (0.00%)  0/248 (0.00%) 
HEPATIC CANCER  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  1/248 (0.40%) 
METASTATIC MALIGNANT MELANOMA  1  1/250 (0.40%)  0/251 (0.00%)  0/251 (0.00%)  0/248 (0.00%) 
NON-SMALL CELL LUNG CANCER  1  1/250 (0.40%)  0/251 (0.00%)  0/251 (0.00%)  0/248 (0.00%) 
PROSTATE CANCER  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  1/248 (0.40%) 
SQUAMOUS CELL CARCINOMA OF SKIN  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  1/250 (0.40%)  1/251 (0.40%)  5/251 (1.99%)  7/248 (2.82%) 
HAEMOPTYSIS  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  1/248 (0.40%) 
LUNG INFILTRATION  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
RESPIRATORY FAILURE  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  1/248 (0.40%) 
Skin and subcutaneous tissue disorders         
ERYTHEMA  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
Vascular disorders         
HYPERTENSIVE CRISIS  1  0/250 (0.00%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
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 QAB149 NVA237 Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   60/250 (24.00%)   51/251 (20.32%)   62/251 (24.70%)   71/248 (28.63%) 
Cardiac disorders         
ATRIAL FIBRILLATION  1  3/250 (1.20%)  0/251 (0.00%)  0/251 (0.00%)  0/248 (0.00%) 
Gastrointestinal disorders         
CONSTIPATION  1  0/250 (0.00%)  0/251 (0.00%)  3/251 (1.20%)  1/248 (0.40%) 
DIARRHOEA  1  0/250 (0.00%)  1/251 (0.40%)  3/251 (1.20%)  0/248 (0.00%) 
DRY MOUTH  1  2/250 (0.80%)  1/251 (0.40%)  0/251 (0.00%)  3/248 (1.21%) 
NAUSEA  1  0/250 (0.00%)  1/251 (0.40%)  2/251 (0.80%)  4/248 (1.61%) 
Immune system disorders         
SEASONAL ALLERGY  1  3/250 (1.20%)  0/251 (0.00%)  1/251 (0.40%)  0/248 (0.00%) 
Infections and infestations         
BRONCHITIS  1  3/250 (1.20%)  5/251 (1.99%)  5/251 (1.99%)  3/248 (1.21%) 
INFLUENZA  1  2/250 (0.80%)  4/251 (1.59%)  1/251 (0.40%)  1/248 (0.40%) 
NASOPHARYNGITIS  1  4/250 (1.60%)  5/251 (1.99%)  7/251 (2.79%)  3/248 (1.21%) 
PHARYNGITIS  1  3/250 (1.20%)  1/251 (0.40%)  1/251 (0.40%)  0/248 (0.00%) 
SINUSITIS  1  0/250 (0.00%)  3/251 (1.20%)  2/251 (0.80%)  2/248 (0.81%) 
UPPER RESPIRATORY TRACT INFECTION  1  6/250 (2.40%)  3/251 (1.20%)  9/251 (3.59%)  7/248 (2.82%) 
UPPER RESPIRATORY TRACT INFECTION BACTERIAL  1  3/250 (1.20%)  6/251 (2.39%)  2/251 (0.80%)  6/248 (2.42%) 
URINARY TRACT INFECTION  1  3/250 (1.20%)  0/251 (0.00%)  4/251 (1.59%)  2/248 (0.81%) 
VIRAL UPPER RESPIRATORY TRACT INFECTION  1  4/250 (1.60%)  2/251 (0.80%)  3/251 (1.20%)  5/248 (2.02%) 
Injury, poisoning and procedural complications         
CONTUSION  1  2/250 (0.80%)  3/251 (1.20%)  1/251 (0.40%)  1/248 (0.40%) 
Musculoskeletal and connective tissue disorders         
BACK PAIN  1  4/250 (1.60%)  2/251 (0.80%)  1/251 (0.40%)  2/248 (0.81%) 
MUSCULOSKELETAL CHEST PAIN  1  0/250 (0.00%)  1/251 (0.40%)  0/251 (0.00%)  3/248 (1.21%) 
Nervous system disorders         
DIZZINESS  1  0/250 (0.00%)  0/251 (0.00%)  3/251 (1.20%)  0/248 (0.00%) 
HEADACHE  1  1/250 (0.40%)  5/251 (1.99%)  2/251 (0.80%)  4/248 (1.61%) 
Psychiatric disorders         
INSOMNIA  1  3/250 (1.20%)  1/251 (0.40%)  1/251 (0.40%)  0/248 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
CHRONIC OBSTRUCTIVE PULMONARY DISEASE  1  28/250 (11.20%)  23/251 (9.16%)  23/251 (9.16%)  36/248 (14.52%) 
COUGH  1  3/250 (1.20%)  3/251 (1.20%)  1/251 (0.40%)  6/248 (2.42%) 
DYSPNOEA  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  3/248 (1.21%) 
OROPHARYNGEAL PAIN  1  5/250 (2.00%)  0/251 (0.00%)  4/251 (1.59%)  3/248 (1.21%) 
SPUTUM INCREASED  1  0/250 (0.00%)  0/251 (0.00%)  0/251 (0.00%)  3/248 (1.21%) 
Vascular disorders         
HYPERTENSION  1  3/250 (1.20%)  2/251 (0.80%)  3/251 (1.20%)  4/248 (1.61%) 
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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01712516     History of Changes
Other Study ID Numbers: CQVA149A2337
First Submitted: October 19, 2012
First Posted: October 23, 2012
Results First Submitted: May 27, 2015
Results First Posted: July 15, 2015
Last Update Posted: July 15, 2015