A Randomized, Multicenter, Open-label, Parallel-group, 12-week Study to Assess the Efficacy and Safety of Switching From Tiotropium to QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) in Symptomatic Mild to Moderate COPD Patients
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT02566031
Collaborator
(none)
379
24
2
62.4
15.8
0.3
Study Details
Study Description
Brief Summary
To demonstrate superiority of QVA149 (110/50 μg) once daily compared to tiotropium 18 μg once daily in terms of trough forced expiratory volume in 1 second (FEV1) (mean of 45 min and 15 min pre-dose) following 12 weeks of treatment in mild to moderate symptomatic COPD patients
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
379 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Multicenter, Open-label, Parallel-group, 12-week Study to Assess the Efficacy and Safety of Switching From Tiotropium to QVA149 (Indacaterol Maleate/Glycopyrronium Bromide) in Symptomatic Mild to Moderate COPD Patients
Actual Study Start Date
:
Mar 23, 2013
Actual Primary Completion Date
:
Jun 4, 2018
Actual Study Completion Date
:
Jun 4, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Indacaterol and glycopyrronium (QVA149) QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks |
Drug: Indacaterol and glycopyrronium (QVA149)
Capsules for inhalation delivered via SDDPI
|
| Active Comparator: Tiotropium Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks |
Drug: Tiotropium
Capsules for inhalation delivered via HandiHaler® device
|
Outcome Measures
Primary Outcome Measures
- Trough Forced Expiratory Volume In One Second (FEV1) After 12 Weeks of Treatment [Week 12]
Spirometry was performed according to internationally accepted standards. Trough FEV1 is defined as the mean of 45 minute and 15 minute pre-dose values.
Secondary Outcome Measures
- Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment [mean of 45 min and 15 min pre-dose week 4]
Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of 45 minute and 15 minute pre-dose values.
- Baseline Transitional Dyspnea Index (TDI) Focal Score [Week 12]
A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. TDI captures changes from baseline, each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.
- Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) [Week 12]
Total score of COPD Assessment Test (CAT) will be measured at week 12. This questionnaire is completed by the patient. The score ranges from 0-40 where higher scores represent worse health status. Mild: Score = 0 - 10, Moderate: Score = 11 - 20, Severe: Score = 21 - 30, Very Severe: Score = 31 - 40. The CAT total score was the sum of 8 item scores (each ranging from 0 to 5). If 1 or 2 items were missing, they were replaced with the mean of the completed items. If 3 or more items were missing, the CAT total score was set missing
- Daily Rescue Medication Use (Number of Puffs) [Week 12]
The total number of puffs of rescue medication used over the last 24 hours will be recorded in the patient diary in the morning. The total number of puffs of rescue medication per day over the full 12 weeks will be calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the patient. The mean daily number of puffs of rescue medication used over 12 weeks will be summarized by treatments
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Confirmed diagnosis of COPD and post-bronchodilator FEV1 ≥ 50% of the predicted normal value and post-bronchodilator FEV1/FVC < 0.7 (COPD Grade 1 or 2 by severity of airflow limitation (GOLD 2015)
-
Patients with CAT score ≥ 10 at Visit 0 and Visit 1.
-
Patients who are on and have been on tiotropium monotherapy for the past 3 months.
-
0 or 1 COPD exacerbation in the previous 12 months (not leading to hospital admission).
Exclusion Criteria:
-
Treatment with any inhaled corticosteroid (ICS) in the 3 months prior to Visit 1.
-
COPD exacerbation between Visit 0 and 1.
-
Patients with concomitant pulmonary disease
-
Patients with a history of respiratory infection within 4 weeks prior to Visit 0.
-
Prior or current diagnosis of asthma.
-
Presence of any contraindication, warning, precaution, hypersensitivity to LABA and LAMA
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Chuncheon | Gangwon-do | Korea, Republic of | 24253 |
| 2 | Novartis Investigative Site | Wonju | Gangwon-Do | Korea, Republic of | 26426 |
| 3 | Novartis Investigative Site | Anyang-si | Gyeonggi-do | Korea, Republic of | 14068 |
| 4 | Novartis Investigative Site | Guri-si | Gyeonggi-do | Korea, Republic of | 471-701 |
| 5 | Novartis Investigative Site | Seongnam-si | Gyeonggi-do | Korea, Republic of | 463-712 |
| 6 | Novartis Investigative Site | Suwon-si | Gyeonggi-do | Korea, Republic of | 16499 |
| 7 | Novartis Investigative Site | Jeonju-si | Jeollabuk-do | Korea, Republic of | 561-712 |
| 8 | Novartis Investigative Site | Seoul | Korea | Korea, Republic of | 03312 |
| 9 | Novartis Investigative Site | Seoul | Korea | Korea, Republic of | 06351 |
| 10 | Novartis Investigative Site | Seoul | Korea | Korea, Republic of | 08308 |
| 11 | Novartis Investigative Site | Koyang | Kyunggi | Korea, Republic of | 410-719 |
| 12 | Novartis Investigative Site | Seoul | Seocho Gu | Korea, Republic of | 06591 |
| 13 | Novartis Investigative Site | Gwangju | Korea, Republic of | 61469 | |
| 14 | Novartis Investigative Site | Incheon | Korea, Republic of | 403-720 | |
| 15 | Novartis Investigative Site | Incheon | Korea, Republic of | 405 760 | |
| 16 | Novartis Investigative Site | Jeju | Korea, Republic of | 63241 | |
| 17 | Novartis Investigative Site | Seoul | Korea, Republic of | 03722 | |
| 18 | Novartis Investigative Site | Seoul | Korea, Republic of | 04763 | |
| 19 | Novartis Investigative Site | Seoul | Korea, Republic of | 05030 | |
| 20 | Novartis Investigative Site | Seoul | Korea, Republic of | 06273 | |
| 21 | Novartis Investigative Site | Seoul | Korea, Republic of | 110-746 | |
| 22 | Novartis Investigative Site | Seoul | Korea, Republic of | 150-713 | |
| 23 | Novartis Investigative Site | Seoul | Korea, Republic of | 156-707 | |
| 24 | Novartis Investigative Site | Ulsan | Korea, Republic of | 44033 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02566031
Other Study ID Numbers:
- CQVA149AKR01
First Posted:
Oct 1, 2015
Last Update Posted:
Sep 23, 2019
Last Verified:
Aug 1, 2019
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Indacaterol and Glycopyrronium (QVA149) | Tiotropium |
|---|---|---|
| Arm/Group Description | QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks |
| Period Title: Overall Study | ||
| STARTED | 189 | 190 |
| COMPLETED | 169 | 178 |
| NOT COMPLETED | 20 | 12 |
Baseline Characteristics
| Arm/Group Title | Indacaterol and Glycopyrronium (QVA149) | Tiotropium | Total |
|---|---|---|---|
| Arm/Group Description | QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks | Total of all reporting groups |
| Overall Participants | 189 | 190 | 379 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
69.2
(8.08)
|
69.0
(7.54)
|
69.1
(7.81)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3
1.6%
|
7
3.7%
|
10
2.6%
|
| Male |
186
98.4%
|
183
96.3%
|
369
97.4%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
189
100%
|
190
100%
|
379
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Trough Forced Expiratory Volume In One Second (FEV1) After 12 Weeks of Treatment |
|---|---|
| Description | Spirometry was performed according to internationally accepted standards. Trough FEV1 is defined as the mean of 45 minute and 15 minute pre-dose values. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization |
| Arm/Group Title | Indacaterol and Glycopyrronium (QVA149) | Tiotropium |
|---|---|---|
| Arm/Group Description | QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks |
| Measure Participants | 177 | 184 |
| Mean (Standard Deviation) [Liters] |
0.0668
(0.18097)
|
0.0090
(0.18487)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Indacaterol and Glycopyrronium (QVA149), Tiotropium |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0129 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 95% 0.011 to 0.093 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Trough Forced Expiratory Volume In One Second (FEV1) After 4 Weeks of Treatment |
|---|---|
| Description | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the mean of 45 minute and 15 minute pre-dose values. |
| Time Frame | mean of 45 min and 15 min pre-dose week 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization |
| Arm/Group Title | Indacaterol and Glycopyrronium (QVA149) | Tiotropium |
|---|---|---|
| Arm/Group Description | QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks |
| Measure Participants | 177 | 184 |
| -45min |
0.087
(0.2386)
|
0.026
(0.1626)
|
| -15min |
0.077
(0.2298)
|
0.024
(0.1567)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Indacaterol and Glycopyrronium (QVA149), Tiotropium |
|---|---|---|
| Comments | -45 min | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0058 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.06 | |
| Confidence Interval |
(2-Sided) 95% 0.017 to 0.098 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Indacaterol and Glycopyrronium (QVA149), Tiotropium |
|---|---|---|
| Comments | -15min | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0161 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.05 | |
| Confidence Interval |
(2-Sided) 95% 0.009 to 0.091 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Baseline Transitional Dyspnea Index (TDI) Focal Score |
|---|---|
| Description | A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. TDI captures changes from baseline, each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization |
| Arm/Group Title | Indacaterol and Glycopyrronium (QVA149) | Tiotropium |
|---|---|---|
| Arm/Group Description | QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks |
| Measure Participants | 177 | 184 |
| Mean (Standard Deviation) [Score] |
0.77
(1.735)
|
0.61
(1.534)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Indacaterol and Glycopyrronium (QVA149), Tiotropium |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0767 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 0.31 | |
| Confidence Interval |
(2-Sided) 95% -0.033 to 0.646 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Change From Baseline on Total Score of COPD Assessment Test (CAT) |
|---|---|
| Description | Total score of COPD Assessment Test (CAT) will be measured at week 12. This questionnaire is completed by the patient. The score ranges from 0-40 where higher scores represent worse health status. Mild: Score = 0 - 10, Moderate: Score = 11 - 20, Severe: Score = 21 - 30, Very Severe: Score = 31 - 40. The CAT total score was the sum of 8 item scores (each ranging from 0 to 5). If 1 or 2 items were missing, they were replaced with the mean of the completed items. If 3 or more items were missing, the CAT total score was set missing |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization |
| Arm/Group Title | Indacaterol and Glycopyrronium (QVA149) | Tiotropium |
|---|---|---|
| Arm/Group Description | QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks |
| Measure Participants | 177 | 184 |
| Mild |
62
32.8%
|
54
28.4%
|
| Moderate |
92
48.7%
|
101
53.2%
|
| Severe |
15
7.9%
|
22
11.6%
|
| Very severe |
0
0%
|
1
0.5%
|
| Missing |
8
4.2%
|
6
3.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Indacaterol and Glycopyrronium (QVA149), Tiotropium |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.1008 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -0.81 | |
| Confidence Interval |
(2-Sided) 95% -1.77 to 0.16 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Daily Rescue Medication Use (Number of Puffs) |
|---|---|
| Description | The total number of puffs of rescue medication used over the last 24 hours will be recorded in the patient diary in the morning. The total number of puffs of rescue medication per day over the full 12 weeks will be calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the patient. The mean daily number of puffs of rescue medication used over 12 weeks will be summarized by treatments |
| Time Frame | Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) consisted of all randomized patients who received at least one dose of study treatment and have at least one evaluable post-baseline assessment. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization |
| Arm/Group Title | Indacaterol and Glycopyrronium (QVA149) | Tiotropium |
|---|---|---|
| Arm/Group Description | QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks |
| Measure Participants | 177 | 184 |
| Mean (Standard Deviation) [Puffs/day] |
1.7
(0.92)
|
1.8
(1.28)
|
Adverse Events
| Time Frame | 12 Weeks | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Indacaterol and Glycopyrronium (QVA149 | Tiotropium | Total | |||
| Arm/Group Description | QVA149 110/50 μg capsules for inhalation delivered once daily via single-dose dry powder inhaler (SDPPI) for 12 weeks | Tiotropium 18 μg capsules for inhalation delivered once daily via HandiHaler® device for 12 weeks | Total | |||
All Cause Mortality |
||||||
| Indacaterol and Glycopyrronium (QVA149 | Tiotropium | Total | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/189 (0%) | 0/188 (0%) | 0/377 (0%) | |||
Serious Adverse Events |
||||||
| Indacaterol and Glycopyrronium (QVA149 | Tiotropium | Total | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/189 (4.2%) | 3/188 (1.6%) | 11/377 (2.9%) | |||
| Cardiac disorders | ||||||
| Angina pectoris | 1/189 (0.5%) | 0/188 (0%) | 1/377 (0.3%) | |||
| Infections and infestations | ||||||
| Pneumonia | 2/189 (1.1%) | 0/188 (0%) | 2/377 (0.5%) | |||
| Injury, poisoning and procedural complications | ||||||
| Femoral neck fracture | 1/189 (0.5%) | 0/188 (0%) | 1/377 (0.3%) | |||
| Fracture | 0/189 (0%) | 1/188 (0.5%) | 1/377 (0.3%) | |||
| Rib fracture | 0/189 (0%) | 1/188 (0.5%) | 1/377 (0.3%) | |||
| Nervous system disorders | ||||||
| Carotid artery stenosis | 1/189 (0.5%) | 0/188 (0%) | 1/377 (0.3%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Chronic obstructive pulmonary disease | 3/189 (1.6%) | 1/188 (0.5%) | 4/377 (1.1%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Indacaterol and Glycopyrronium (QVA149 | Tiotropium | Total | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 12/189 (6.3%) | 9/188 (4.8%) | 21/377 (5.6%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Chronic obstructive pulmonary disease | 12/189 (6.3%) | 9/188 (4.8%) | 21/377 (5.6%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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 | 8627788300 |
| novartis.email@novartis.com |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT02566031
Other Study ID Numbers:
- CQVA149AKR01
First Posted:
Oct 1, 2015
Last Update Posted:
Sep 23, 2019
Last Verified:
Aug 1, 2019