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Clinical Trial Results:
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.

Summary
EudraCT number	2012-003346-32
Trial protocol	ES PL
Global end of trial date	28 Feb 2014

Results information
Results version number	v1(current)
This version publication date	13 Jul 2016
First version publication date	25 Jul 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CQVA149A2336

ISRCTN number

US NCT number

NCT01727141

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharmaceuticals AG, CH-4002, Basel, Switzerland

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Novartis Pharmaceuticals AG, Novartis Pharmaceuticals AG, Novartis Pharmaceuticals AG, Novartis Pharmaceuticals AG, 41 613241111,

Scientific contact

Novartis Pharmaceuticals AG, Novartis Pharmaceuticals AG, Novartis Pharmaceuticals AG, Novartis Pharmaceuticals AG, 41 613241111,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

28 Feb 2014

Is this the analysis of the primary completion data?

Yes

Primary completion date

28 Feb 2014

Global end of trial reached?

Yes

Global end of trial date

28 Feb 2014

Was the trial ended prematurely?

Main objective of the trial

To demonstrate the superiority of QVA149 27.5/12.5 ug b.i.d. compared to monotherpay components, QAB149 27.5 ug b.i.d and NVA237 12.5 ug b.i.d., in terms of standardized FEV1 AUC0-12 h at week 12. Eligible patients were provided a short acting β2-agonist (salbutamol or albuterol) for use as a rescue inhaler on an “as needed” basis throughout the study.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Nov 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 126

Country: Number of subjects enrolled

Philippines: 26

Country: Number of subjects enrolled

Poland: 28

Country: Number of subjects enrolled

Romania: 101

Country: Number of subjects enrolled

Spain: 96

Country: Number of subjects enrolled

Ukraine: 147

Country: Number of subjects enrolled

United States: 510

Country: Number of subjects enrolled

Vietnam: 8

Worldwide total number of subjects

1042

EEA total number of subjects

225

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

558

From 65 to 84 years

481

85 years and over

Subject disposition

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Recruitment details

Participants were randomized to each treatment arm in a 1:1:1:1 ratio.

Screening details

One thousand forty two participants were randomized. (One participant was randomized twice and was counted twice in the randomized set.) In the safety set, participants were analyzed according to the treatment received.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

QVA149

Arm description

27.5/12.5 ug twice daily (b.i.d) Single Dose Dry Powder Inhaler (SDDPI)

Arm type

Experimental

Investigational medicinal product name

QVA149

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Inhalation use

Dosage and administration details

27.5/12.5 ug twice daily (b.i.d.) Single Dose Dry Powder Inhaler (SDDPI)

QAB149

Arm description

27.5 ug b.i.d.

Arm type

Active comparator

Investigational medicinal product name

QAB149

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Inhalation use

Dosage and administration details

27.5 ug b.i.d.

NVA237

Arm description

12.5 ug b.i.d.

Arm type

Active comparator

Investigational medicinal product name

NVA237

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Inhalation use

Dosage and administration details

12.5 ug b.i.d.

Placebo

Arm description

b.i.d

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Inhalation use

Dosage and administration details

b.i.d.

Number of subjects in period 1	QVA149	QAB149	NVA237	Placebo
Started	260	260	261	261
Full analysis set	258	260	261	261
Safety set	258	260	261	260
Completed	255	251	258	246
Not completed	5	9	3	15
Adverse event, serious fatal	-	1	1	1
Consent withdrawn by subject	4	4	2	11
Physician decision	-	1	-	2
Protocol deviation	1	1	-	1
Lost to follow-up	-	2	-	-

Baseline characteristics

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Reporting group title

QVA149

Reporting group description

27.5/12.5 ug twice daily (b.i.d) Single Dose Dry Powder Inhaler (SDDPI)

Reporting group title

QAB149

Reporting group description

27.5 ug b.i.d.

Reporting group title

NVA237

Reporting group description

12.5 ug b.i.d.

Reporting group title

Placebo

Reporting group description

b.i.d

Reporting group values	QVA149	QAB149	NVA237	Placebo	Total
Number of subjects	260	260	261	261	1042
Age categorical
Units: Subjects
In utero	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0
Adults (18-64 years)	132	143	140	143	558
From 65-84 years	126	116	121	118	481
85 years and over	2	1	0	0	3
Age Continuous \|
Units: Years
arithmetic mean (standard deviation)	63.9 ± 8.76	63.7 ± 8.07	63.7 ± 8.35	63.7 ± 8.19	-
Gender, Male/Female
Units: Participants
Female	90	74	78	92	334
Male	170	186	183	169	708

End points

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Reporting group title

QVA149

Reporting group description

27.5/12.5 ug twice daily (b.i.d) Single Dose Dry Powder Inhaler (SDDPI)

Reporting group title

QAB149

Reporting group description

27.5 ug b.i.d.

Reporting group title

NVA237

Reporting group description

12.5 ug b.i.d.

Reporting group title

Placebo

Reporting group description

b.i.d

Primary: Change from baseline in standardized forced expiratory volume in 1 second (FEV1) Area Under the Curve (AUC) (0-12 hours (h))

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End point title

Change from baseline in standardized forced expiratory volume in 1 second (FEV1) Area Under the Curve (AUC) (0-12 hours (h))

End point 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.

End point type

Primary

End point timeframe

baseline (BL), 12 Weeks

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	258	260	261	260
Units: Liter
least squares mean (standard error)	0.211 ± 0.014	0.117 ± 0.014	0.112 ± 0.0141	-0.021 ± 0.0145

FEV1 (L) AUC(0-12h) change from baseline

Comparison groups

QAB149 v QVA149

Number of subjects included in analysis

518

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed model for repeated measures (MMRM)

Confidence interval

FEV1 (L) AUC(0-12h) change from baseline

Comparison groups

QVA149 v NVA237

Number of subjects included in analysis

519

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Mixed model for repeated measures (MMRM)

Confidence interval

Secondary: Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score

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End point title

Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score

End point 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.

End point type

Secondary

End point timeframe

BL, 12 Weeks

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	246	244	243	223
Units: score on a scale
least squares mean (standard error)	-6.4 ± 0.75	-4.6 ± 0.75	-4.8 ± 0.75	-2.7 ± 0.78

No statistical analyses for this end point

Secondary: Percentage of participants with a clinically important improvement of at least 4 units in the SGRQ total score

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End point title

Percentage of participants with a clinically important improvement of at least 4 units in the SGRQ total score

End point description

End point type

Secondary

End point timeframe

12 weeks

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	246	244	243	223
Units: Percentage of participants
number (not applicable)	57.3	48	46.1	39

No statistical analyses for this end point

Secondary: Change from baseline in trough FEV1

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End point title

Change from baseline in trough FEV1

End point 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.

End point type

Secondary

End point timeframe

BL, day 2, day 86

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	256	257	260	252
Units: Liters
least squares mean (standard error)
day 2	0.187 ± 0.0102	0.109 ± 0.0102	0.112 ± 0.0101	0.015 ± 0.0103
day 86	0.201 ± 0.0144	0.12 ± 0.0142	0.092 ± 0.0142	-0.012 ± 0.015

No statistical analyses for this end point

Secondary: Change from baseline in pre-dose trough FEV1

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End point title

Change from baseline in pre-dose trough FEV1

End point 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.

End point type

Secondary

End point timeframe

BL, day 85

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	254	254	257	244
Units: Liters
least squares mean (standard error)	0.161 ± 0.014	0.083 ± 0.014	0.061 ± 0.014	-0.035 ± 0.0145

No statistical analyses for this end point

Secondary: Change from baseline in FEV1

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End point title

Change from baseline in FEV1

End point description

End point type

Secondary

End point timeframe

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, 11h55min;Day 86: 23h15min; 23h45min

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	258	260	261	261
Units: Liters
least squares mean (standard error)
Day 1, 5 min (n=255,257,260,255)	0.111 ± 0.0062	0.071 ± 0.0062	0.065 ± 0.0062	0.009 ± 0.0062
Day 1, 15 min (n=256,256,261,258)	0.146 ± 0.007	0.088 ± 0.007	0.117 ± 0.0069	0.012 ± 0.007
Day 1, 1 h (n=258,260,261,258)	0.179 ± 0.0082	0.085 ± 0.0082	0.166 ± 0.0081	0.016 ± 0.0082
Day 1, 2 h (n=254,257,261,254)	0.219 ± 0.0091	0.104 ± 0.0091	0.179 ± 0.0089	0.037 ± 0.009
Day 1, 4 h (n=252,260,256,254)	0.207 ± 0.0103	0.105 ± 0.0103	0.146 ± 0.0101	0.039 ± 0.0103
Day 1, 6 h (n=253,256,254,248)	0.178 ± 0.0105	0.102 ± 0.0105	0.125 ± 0.0104	0.021 ± 0.0107
Day 1, 8 h (n=253,251,256,248)	0.157 ± 0.01	0.081 ± 0.0102	0.106 ± 0.0101	0.004 ± 0.0104
Day 1, 11 h (n=246,250,253,245)	0.116 ± 0.0112	0.047 ± 0.0112	0.073 ± 0.0111	-0.02 ± 0.0113
Day 2, 23h 15 min (n=249,249,254,242)	0.176 ± 0.0106	0.104 ± 0.0106	0.106 ± 0.0104	0.004 ± 0.0107
Day 2, 23h 45min (n= 255,254,258,250)	0.194 ± 0.0108	0.119 ± 0.0109	0.119 ± 0.0107	0.022 ± 0.011
Day 15, -45min (n=254,254,256,244)	0.168 ± 0.0123	0.114 ± 0.0124	0.067 ± 0.0122	-0.023 ± 0.0126
Day 15, -15 min (n=254,254,256,243)	0.185 ± 0.0125	0.139 ± 0.0126	0.087 ± 0.0125	-0.008 ± 0.0129
Day 15, 1 h (n=258,260,261,258)	0.269 ± 0.0133	0.173 ± 0.0134	0.161 ± 0.0133	0.004 ± 0.0136
Day 29, -45 min (n=254,254,256,244)	0.175 ± 0.0123	0.111 ± 0.0124	0.073 ± 0.0123	-0.029 ± 0.0126
Day 29, -15 min (n=254,254,256,243)	0.193 ± 0.0128	0.131 ± 0.0127	0.092 ± 0.0127	-0.006 ± 0.013
Day 29, 1 h (n=258,260, 261,258)	0.271 ± 0.0135	0.167 ± 0.0135	0.156 ± 0.0135	0.006 ± 0.0138
Day 57, -45 min (n=254,254,256,244)	0.181 ± 0.0134	0.097 ± 0.0134	0.069 ± 0.0133	-0.016 ± 0.0137
Day 57, -15 min (n=254,254,256,243)	0.193 ± 0.0132	0.117 ± 0.0132	0.094 ± 0.0132	0.006 ± 0.0136
Day 57, 1 h (n=258,260,261,258)	0.273 ± 0.0141	0.15 ± 0.0141	0.161 ± 0.014	0.008 ± 0.0144
Day 85, -45 min (n= 254,254,256,244)	0.154 ± 0.0142	0.08 ± 0.0142	0.051 ± 0.0142	-0.038 ± 0.0146
Day 85, -15 min (n=254,254,256,243)	0.171 ± 0.0144	0.088 ± 0.0144	0.073 ± 0.0143	-0.035 ± 0.0149
Day 85, 5 min (n=255,257,260,255)	0.232 ± 0.0147	0.119 ± 0.0148	0.106 ± 0.0149	-0.036 ± 0.0154
Day 85, 15 min (n=256,256,261,258)	0.242 ± 0.015	0.143 ± 0.0151	0.13 ± 0.0152	-0.02 ± 0.0159
Day 85, 1 h (n=258,260,261,258)	0.25 ± 0.0149	0.136 ± 0.0149	0.15 ± 0.015	-0.021 ± 0.0154
Day 85, 2 h 9n=254,257,261,254)	0.265 ± 0.015	0.145 ± 0.015	0.171 ± 0.0151	-0.009 ± 0.0157
Day 85, 4 h (n=252,260,256,254)	0.242 ± 0.0158	0.14 ± 0.0155	0.132 ± 0.0158	-0.001 ± 0.0165
Day 85, 6 h (n=253,256,254,248)	0.197 ± 0.0154	0.123 ± 0.0155	0.109 ± 0.0157	-0.017 ± 0.0162
Day 85, 8 h (n=253,251,256,248)	0.18 ± 0.0152	0.103 ± 0.0152	0.086 ± 0.0151	-0.03 ± 0.0158
Day 85, 11 h 55min(n=246,250,253,245)	0.143 ± 0.0155	0.066 ± 0.0154	0.055 ± 0.015	-0.064 ± 0.0161
Day 86, 23 h 15 min (n=249,249,254,242)	0.196 ± 0.0149	0.116 ± 0.0151	0.082 ± 0.0151	-0.017 ± 0.0155
Day 86, 23 h 45 min (n=255,254,258,250)	0.216 ± 0.0144	0.128 ± 0.0144	0.1 ± 0.0143	-0.004 ± 0.015

No statistical analyses for this end point

Secondary: Change from baseline in FVC

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End point title

Change from baseline in FVC

End point 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.

End point type

Secondary

End point timeframe

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 55min;Day 86: 23h15min; 23h45min

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	258	260	261	261
Units: Liters
least squares mean (standard error)
Day 1, 5 min (n=255,257,260,255)	0.234 ± 0.0131	0.175 ± 0.0132	0.136 ± 0.0131	0.009 ± 0.0131
Day 1, 15 min (n=256,256,261,258)	0.283 ± 0.0146	0.2 ± 0.0146	0.243 ± 0.0145	0.032 ± 0.0146
Day 1, 1 h (n=258,260,261,258)	0.329 ± 0.0165	0.191 ± 0.0164	0.292 ± 0.0163	0.029 ± 0.0164
Day 1, 2 h (n=254,257,261,254)	0.39 ± 0.018	0.22 ± 0.018	0.306 ± 0.0177	0.076 ± 0.0178
Day 1, 4 h (n=252,260,256,254)	0.355 ± 0.0192	0.209 ± 0.0192	0.253 ± 0.019	0.072 ± 0.0192
Day 1, 6 h (n=253,256,254,248)	0.319 ± 0.0198	0.214 ± 0.0198	0.23 ± 0.0197	0.043 ± 0.0202
Day 1, 8 h (n=253,251,256,248)	0.306 ± 0.0189	0.188 ± 0.0192	0.195 ± 0.0189	0.04 ± 0.0195
Day 1, 11 h 55 min(n=246,250,253,245)	0.24 ± 0.0208	0.122 ± 0.0208	0.14 ± 0.0207	-0.019 ± 0.021
Day 2, 23 h 15 min (n=249,249,254,242)	0.315 ± 0.0194	0.214 ± 0.0193	0.19 ± 0.019	0.013 ± 0.0196
Day 2, 23 h 45 min (n=255,254,258,250)	0.337 ± 0.02	0.232 ± 0.0203	0.201 ± 0.0198	0.056 ± 0.023
Day 15, -45 min (n=254,254,256,244)	0.265 ± 0.0227	0.188 ± 0.0229	0.134 ± 0.0225	-0.016 ± 0.0232
Day 15, -15 min (n=254,254,256,243)	0.307 ± 0.0234	0.206 ± 0.0236	0.167 ± 0.0233	0.032 ± 0.0241
Day 15, 1 h (n=258,260,261,258)	0.419 ± 0.0241	0.274 ± 0.0242	0.269 ± 0.0241	0.034 ± 0.0246
Day 29, -45 min (n=254,254,256,244)	0.276 ± 0.0225	0.177 ± 0.0226	0.142 ± 0.0224	-0.022 ± 0.0231
Day 29, -15 min (n=254,254,256,243)	0.304 ± 0.0228	0.203 ± 0.0228	0.168 ± 0.0227	0.017 ± 0.0233
Day 29, 1 h (n=258,260,261,258)	0.422 ± 0.0243	0.259 ± 0.0244	0.272 ± 0.0243	0.046 ± 0.0248
Day 57, -45 min (n=254,254,256,244)	0.286 ± 0.0235	0.153 ± 0.0236	0.124 ± 0.0234	-0.026 ± 0.024
Day 57, -15 min (n=254,254,256,243)	0.299 ± 0.0234	0.177 ± 0.0234	0.172 ± 0.0234	0.022 ± 0.0241
Day 57, 1 h (n=258,260,261,258)	0.411 ± 0.0241	0.239 ± 0.0241	0.265 ± 0.024	0.03 ± 0.0246
Day 85, -45 min (n=254,254,256,244)	0.247 ± 0.0245	0.106 ± 0.0245	0.092 ± 0.0245	-0.055 ± 0.0252
Day 85, -15 min (n=254,254,256,243)	0.264 ± 0.0246	0.129 ± 0.0247	0.134 ± 0.0245	-0.058 ± 0.0255
Day 85, 5 min (n=255,257,260,255)	0.35 ± 0.0253	0.192 ± 0.0255	0.179 ± 0.0255	-0.031 ± 0.0265
Day 85, 15 min (n=256,256,261,258)	0.378 ± 0.025	0.226 ± 0.0252	0.226 ± 0.0252	-0.011 ± 0.0263
Day 85, 1 h (n=258,260,261,258)	0.366 ± 0.025	0.2 ± 0.025	0.243 ± 0.0251	-0.024 ± 0.0257
Day 85, 2 h (n=254,257,261,254)	0.38 ± 0.0255	0.222 ± 0.0255	0.285 ± 0.0255	0.012 ± 0.0265
Day 85, 4 h (n=252,260,256,254)	0.326 ± 0.026	0.201 ± 0.0255	0.203 ± 0.0259	0.008 ± 0.027
Day 85, 6 h (n=253,256,254,248)	0.29 ± 0.0263	0.164 ± 0.0265	0.176 ± 0.0268	-0.033 ± 0.0276
Day 85, 8h (n=253,251,256,248)	0.263 ± 0.0259	0.154 ± 0.0259	0.155 ± 0.0258	-0.035 ± 0.0269
Day 85, 11 55 min (n=246,250,253,245)	0.209 ± 0.0261	0.109 ± 0.0259	0.11 ± 0.0253	-0.071 ± 0.0271
Day 86, 23 h 15 min (n=249,249,254,242)	0.295 ± 0.025	0.16 ± 0.0254	0.142 ± 0.0253	-0.007 ± 0.0259
Day 86, 23 h 45 min (n=255,254,258,250)	0.315 ± 0.0243	0.186 ± 0.0242	0.167 ± 0.024	0.029 ± 0.0251

No statistical analyses for this end point

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)

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End point title

Change from baseline in standardized FEV1 AUC (0-4 h), FEV1 AUC (4-8h), FEV1 AUC (8-12h) and FEV1 AUC (0-12 h)

End point 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.

End point type

Secondary

End point timeframe

BL, day 1, week 12

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	258	260	261	261
Units: Liters
least squares mean (standard error)
day 1, FEV1 AUC 0-4h (n=249,251,250,246)	0.194 ± 0.0077	0.096 ± 0.0077	0.158 ± 0.0077	0.028 ± 0.0077
day 1, FEV1 AUC 4-8h (n=257,260,261,257)	0.178 ± 0.0093	0.096 ± 0.0093	0.125 ± 0.0093	0.023 ± 0.0093
day 1, FEV1 AUC 8-12h (n=254,256,259,253)	0.138 ± 0.0097	0.065 ± 0.0098	0.094 ± 0.0097	-0.006 ± 0.0098
day 1, FEV1 AUC 0-12h (n=249,251,250,246)	0.171 ± 0.0083	0.083 ± 0.0083	0.128 ± 0.0082	0.016 ± 0.0083
week 12, FEV1 AUC 0-4h (n=249,251,250,246)	0.254 ± 0.0144	0.141 ± 0.0144	0.149 ± 0.0145	-0.01 ± 0.015
week 12, FEV1 AUC 4-8h (n=257,260,261,257)	0.205 ± 0.0145	0.121 ± 0.0144	0.111 ± 0.0145	-0.016 ± 0.0151
week 12, FEV1 AUC 8-12h (n=254,256,259,253)	0.164 ± 0.0145	0.084 ± 0.0144	0.072 ± 0.0143	-0.043 ± 0.0151
week 12, FEV1 AUC 0-12h (n=249,251,250,246)	0.211 ± 0.014	0.117 ± 0.014	0.112 ± 0.0141	-0.021 ± 0.0145

No statistical analyses for this end point

Secondary: Transitional Dyspnea Index (TDI) focal score

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End point title

Transitional Dyspnea Index (TDI) focal score

End point 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.

End point type

Secondary

End point timeframe

BL, 12 weeks

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	246	240	246	226
Units: score on a scale
least squares mean (standard error)	1.94 ± 0.211	1.3 ± 0.212	1.48 ± 0.21	0.71 ± 0.217

No statistical analyses for this end point

Secondary: Change from baseline in mean daily number of puffs of rescue medication

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End point title

Change from baseline in mean daily number of puffs of rescue medication

End point 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.

End point type

Secondary

End point timeframe

BL, 12 Weeks

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	251	250	252	240
Units: Number of puffs
least squares mean (standard error)	-2.22 ± 0.135	-1.72 ± 0.135	-1.65 ± 0.135	-1 ± 0.137

No statistical analyses for this end point

Secondary: Change from baseline in mean total daily symptom score, mean daytime total symptom score and mean nighttime total symptom score

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End point title

Change from baseline in mean total daily symptom score, mean daytime total symptom score and mean nighttime total symptom score

End point 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 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.

End point type

Secondary

End point timeframe

BL, 12 Weeks

End point values	QVA149	QAB149	NVA237	Placebo
Number of subjects analysed	258	260	261	261
Units: score on a scale
least squares mean (standard error)
Daily (n=251,250,252,240)	-1.3 ± 0.104	-0.97 ± 0.104	-0.99 ± 0.104	-0.52 ± 0.106
Daytime (n=245,246,245,238)	-1.17 ± 0.102	-0.85 ± 0.102	-0.88 ± 0.102	-0.38 ± 0.103
Nighttime (n=244,248,248,234)	-1.07 ± 0.106	-0.83 ± 0.105	-0.85 ± 0.105	-0.4 ± 0.107

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit

Adverse event reporting additional description

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

QVA149 27.5/12.5 mcg

Reporting group description

QVA149 27.5/12.5 mcg

Reporting group title

QAB149 27.5 mcg

Reporting group description

QAB149 27.5 mcg

Reporting group title

NVA237 12.5 mcg

Reporting group description

NVA237 12.5 mcg

Reporting group title

Placebo

Reporting group description

Placebo

Serious adverse events	QVA149 27.5/12.5 mcg	QAB149 27.5 mcg	NVA237 12.5 mcg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 258 (3.88%)	13 / 260 (5.00%)	8 / 262 (3.05%)	8 / 260 (3.08%)
number of deaths (all causes)	0	2	1	1
number of deaths resulting from adverse events	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLADDER TRANSITIONAL CELL CARCINOMA
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
SMALL CELL LUNG CANCER
subjects affected / exposed	1 / 258 (0.39%)	0 / 260 (0.00%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
PERIPHERAL ISCHAEMIA
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
NON-CARDIAC CHEST PAIN
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
ANAPHYLACTIC REACTION
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	0 / 262 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	1 / 262 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ASPIRATION
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
subjects affected / exposed	2 / 258 (0.78%)	5 / 260 (1.92%)	4 / 262 (1.53%)	3 / 260 (1.15%)
occurrences causally related to treatment / all	0 / 2	0 / 5	0 / 4	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
RESPIRATORY FAILURE
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	0 / 262 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Investigations
ALANINE AMINOTRANSFERASE INCREASED
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	1 / 262 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	1 / 258 (0.39%)	0 / 260 (0.00%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
GAMMA-GLUTAMYLTRANSFERASE INCREASED
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	1 / 262 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
ALCOHOL POISONING
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
ANGINA PECTORIS
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
ATRIAL FIBRILLATION
subjects affected / exposed	2 / 258 (0.78%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
CARDIAC ARREST
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
CARDIO-RESPIRATORY ARREST
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Nervous system disorders
BRAIN INJURY
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
CEREBROVASCULAR ACCIDENT
subjects affected / exposed	1 / 258 (0.39%)	0 / 260 (0.00%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
CONVULSION
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	1 / 262 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
LACUNAR INFARCTION
subjects affected / exposed	1 / 258 (0.39%)	0 / 260 (0.00%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
MIGRAINE
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
NORMOCHROMIC NORMOCYTIC ANAEMIA
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	1 / 262 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
COLITIS
subjects affected / exposed	1 / 258 (0.39%)	0 / 260 (0.00%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
INTESTINAL OBSTRUCTION
subjects affected / exposed	1 / 258 (0.39%)	0 / 260 (0.00%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
SMALL INTESTINAL OBSTRUCTION
subjects affected / exposed	1 / 258 (0.39%)	0 / 260 (0.00%)	0 / 262 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
BILIARY COLIC
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	0 / 262 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
RENAL FAILURE
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	1 / 262 (0.38%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
RENAL FAILURE ACUTE
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Infections and infestations
INFLUENZA
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	0 / 262 (0.00%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	0 / 258 (0.00%)	0 / 260 (0.00%)	2 / 262 (0.76%)	1 / 260 (0.38%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
UPPER RESPIRATORY TRACT INFECTION BACTERIAL
subjects affected / exposed	1 / 258 (0.39%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
URINARY TRACT INFECTION
subjects affected / exposed	0 / 258 (0.00%)	1 / 260 (0.38%)	0 / 262 (0.00%)	0 / 260 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	QVA149 27.5/12.5 mcg	QAB149 27.5 mcg	NVA237 12.5 mcg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	58 / 258 (22.48%)	57 / 260 (21.92%)	64 / 262 (24.43%)	62 / 260 (23.85%)
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
subjects affected / exposed	46 / 258 (17.83%)	52 / 260 (20.00%)	60 / 262 (22.90%)	59 / 260 (22.69%)
occurrences all number	66	66	86	96
Infections and infestations
NASOPHARYNGITIS
subjects affected / exposed	17 / 258 (6.59%)	8 / 260 (3.08%)	5 / 262 (1.91%)	6 / 260 (2.31%)
occurrences all number	20	10	5	6

More information

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Were there any global substantial amendments to the protocol? Yes

31 May 2013

Amendment 1: The purpose of the amendment was to ensure that there was no overlap of patients between this trial and the replicate trial, QVA149A2337, which would protect the integrity of both trials. An exclusion criterion was added to the current trial, which excluded patients who previously enrolled in QVA149A2337. Changes were made to the analyses used to evaluate the primary endpoint as follows: 1) a 2-way interaction between baseline and visit in the model was added in order to account for the difference in correlation between the outcome and baseline at each visit; and 2) the sensitivity analysis based only on the completers at week 12 was removed as the underlying assumption of data being missing completely at random was too restrictive. In addition, patients with moderate renal impairment were allowed to participate in the trial, ensuring that the protocol population was not too restrictive.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
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.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline in standardized forced expiratory volume in 1 second (FEV1) Area Under the Curve (AUC) (0-12 hours (h))

Primary: Change from baseline in standardized forced expiratory volume in 1 second (FEV1) Area Under the Curve (AUC) (0-12 hours (h))

Secondary: Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score

Secondary: Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score

Secondary: Percentage of participants with a clinically important improvement of at least 4 units in the SGRQ total score

Secondary: Percentage of participants with a clinically important improvement of at least 4 units in the SGRQ total score

Secondary: Change from baseline in trough FEV1

Secondary: Change from baseline in trough FEV1

Secondary: Change from baseline in pre-dose trough FEV1

Secondary: Change from baseline in pre-dose trough FEV1

Secondary: Change from baseline in FEV1

Secondary: Change from baseline in FEV1

Secondary: Change from baseline in FVC

Secondary: Change from baseline in FVC

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)

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)

Secondary: Transitional Dyspnea Index (TDI) focal score

Secondary: Transitional Dyspnea Index (TDI) focal score

Secondary: Change from baseline in mean daily number of puffs of rescue medication

Secondary: Change from baseline in mean daily number of puffs of rescue medication

Secondary: Change from baseline in mean total daily symptom score, mean daytime total symptom score and mean nighttime total symptom score

Secondary: Change from baseline in mean total daily symptom score, mean daytime total symptom score and mean nighttime total symptom score

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Cyprus
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Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
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Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
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Outside EU/EEA

Clinical trials

Clinical Trial Results: 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.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline in standardized forced expiratory volume in 1 second (FEV1) Area Under the Curve (AUC) (0-12 hours (h))

Primary: Change from baseline in standardized forced expiratory volume in 1 second (FEV1) Area Under the Curve (AUC) (0-12 hours (h))

Secondary: Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score

Secondary: Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score

Secondary: Percentage of participants with a clinically important improvement of at least 4 units in the SGRQ total score

Secondary: Percentage of participants with a clinically important improvement of at least 4 units in the SGRQ total score

Secondary: Change from baseline in trough FEV1

Secondary: Change from baseline in trough FEV1

Secondary: Change from baseline in pre-dose trough FEV1

Secondary: Change from baseline in pre-dose trough FEV1

Secondary: Change from baseline in FEV1

Secondary: Change from baseline in FEV1

Secondary: Change from baseline in FVC

Secondary: Change from baseline in FVC

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)

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)

Secondary: Transitional Dyspnea Index (TDI) focal score

Secondary: Transitional Dyspnea Index (TDI) focal score

Secondary: Change from baseline in mean daily number of puffs of rescue medication

Secondary: Change from baseline in mean daily number of puffs of rescue medication

Secondary: Change from baseline in mean total daily symptom score, mean daytime total symptom score and mean nighttime total symptom score

Secondary: Change from baseline in mean total daily symptom score, mean daytime total symptom score and mean nighttime total symptom score

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
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.