A Phase 3 interventional study of QVA149 and Placebo to tiotropium in Chronic Obstructive Pulmonary Disease (COPD), sponsored by Novartis Pharmaceuticals. Completed at 144 sites in Germany. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2014-05-22.
Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 3, Interventional, and Treatment
This study will assess the efficacy and safety of QVA149 compared to tiotropium plus formoterol in patients with moderate to severe COPD.
4,252 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 707 are open to participants now.
This study's enrollment of 934 is above the median of 70 across 3,008 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.
Browse Pulmonary Disease, Chronic Obstructive studies →Novartis Pharmaceuticals is the lead sponsor of 2,711 studies on the registry; 218 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 435 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
QVA149 110/50µg, once daily for inhalation use plus placebo to tiotropium, once daily for inhalation use and placebo to formoterol, twice daily for inhalation use.
Drug: QVA149 · Drug: Placebo to tiotropium · Drug: Placebo to formoterol
Tiotropium 18µg, once daily for inhalation use plus Formoterol 12µg, twice daily for inhalation use and placebo to QVA149, once daily for inhalation use.
Drug: Tiotropium · Drug: Formoterol · Drug: Placebo to QVA149
QVA149 110/50µg, once daily (q.d.) is administered via a single-dose dry powder inhaler
Placebo to tiotropium capsules daily (q.d.) for inhalation, delivered via proprietary inhaler (Handihaler®). Placebo tiotropium inhalation capsules were matched in size and color to tiotropium 18 μg q.d. inhalation capsules
Placebo to formoterol capsules twice daily (b.i.d) delivered via Aerolizer® device. Placebo formoterol inhalation capsules were equally matched in size, shape and color to formoterol 12 μg b.i.d. inhalation capsules.
Tiotropium 18µg, once daily is administered via the manufacturer's proprietary inhalation device.
Formoterol 12µg, twice daily is administered via the manufacturer's proprietary inhalation device.
Placebo to QVA149 is administered via a single-dose dry powder inhaler. Placebo QVA149 inhalation capsules were equally matched in size, shape and color to QVA149 110/50 μg q.d. inhalation capsules
St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Non-inferiority Analysis).
SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative.
Time frame: Baseline, week 26
St. George's Respiratory Questionnaire (SGRQ-C) Total Score After 26 Weeks of Treatment (Superiority Analysis).
SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative. Superiority of QVA 110/50 μg to tiotropium 18 μg q.d. plus formoterol 12 μg b.i.d. in terms of health related quality of life as assessed by St George's Respiratory Questionnaire (SGRQ-C) after 26 weeks of treatment
Time frame: Baseline, week 26
Transition Dyspnea Index (TDI) Focal Score After 26 Weeks of Treatment.
Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI) focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). 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. missing values were replaced by the latest observed value (LOCF)
Time frame: Week 26
Percent of Participants With at Least One Exacerbation Requiring Systemic Corticosteroids and/or Antibiotics Over 26 Weeks
The percent of participants with at least one moderate exacerbation within the 26 weeks that required systemic corticosteroids and/or antibiotics during the treatment
Time frame: Week 26
Percent of Participants With at Least One Exacerbation Requiring Hospitalization
The percent of patients with at least one severe exacerbation within the 26 weeks that required hospitalization. COPD exacerbations were considered to be severe if hospitalization were required.
Time frame: Week 26
Time- Event Analysis, Number of Participants With at Least One COPD Exacerbation (Moderate or Severe) During the Treatment Period
The number of participants with at least one moderate or severe COPD exacerbation. COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required.
Time frame: Week 26
Trough FEV1 at Baseline and Week 26
Trough FEV1 is the mean value of FEV1 (forced expiratory volume in one second) measured at 23:15h and 23:45h after the morning doses. The baseline value was measured at day 1 prior to the first dose.
Time frame: Baseline, Week 26
FEV1 30 Min After the Morning Dose at Baseline and Week 26
FEV1 30min is the forced expiratory volume in one second measured 30 min after the morning dose.
Time frame: Baseline, Week 26
Symptoms Score Reported by the Patients Using Part I "Symptoms" of SGRO-C
Part I of the SGRQ-C covers "symptoms" and is concerned with respiratory symptoms, their frequency and severity. Each questionnaire response has a unique empirically derived "weight". A score was calculated from these weights. The lowest possible value is zero and the highest 100. A higher value corresponds to greater impairment of health status.
Time frame: Baseline, Week 26
| Milestone | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Started | 476 | 458 |
| Full analysis set (fas) | 476 | 458 |
| Per protocol set (pps) | 373 | 374 |
| Completed | 415 | 406 |
| Not completed | 61 | 52 |
| Withdrew: Lost to follow-up | 2 | 4 |
| Withdrew: Administrative problems | 0 | 1 |
| Withdrew: Death | 3 | 3 |
| Withdrew: Patient's inability to use the device | 0 | 1 |
| Withdrew: Adverse event | 36 | 27 |
| Withdrew: Abnormal laboratory value(s) | 1 | 0 |
| Withdrew: Abnormal test procedure result(s) | 1 | 1 |
| Withdrew: Unsatisfactory therapeutic effect | 6 | 0 |
| Withdrew: Protocol violation | 3 | 5 |
| Withdrew: Withdrawal by subject | 9 | 10 |
SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative.
| Score on a scale | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Baseline (n=452,441) | 44.70 ± 17.718 | 45.68 ± 17.720 |
| Week 26 (n=475,456) | 41.30 ± 19.923 | 43.19 ± 19.284 |
SGRQ is a health related quality of life questionnaire consisting of 40 items in three areas: symptoms (respiratory symptoms and severity), activity (activities that cause or are limited by breathlessness) and impacts (social functioning and psychological disturbances due to airway disease). The total score is 0 to 100 with a higher score indicating poorer health status. For patients who completed the study but with missing SGRQ-C during treatment, the missing SGRQ-C were replaced by the last observation carried forward (LOCF). Symptom scores were expected to improve over treatment, therefore the replacement of missing values with earlier measurements did not result in overoptimistic imputation and this procedure could be regarded as conservative. Superiority of QVA 110/50 μg to tiotropium 18 μg q.d. plus formoterol 12 μg b.i.d. in terms of health related quality of life as assessed by St George's Respiratory Questionnaire (SGRQ-C) after 26 weeks of treatment
| Score on a scale | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Baseline (n=452,441) | 44.70 ± 17.718 | 45.68 ± 17.720 |
| Week 26 (n=475,456) | 41.30 ± 19.923 | 43.19 ± 19.284 |
Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI) focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). 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. missing values were replaced by the latest observed value (LOCF)
| Units on a scale | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Transition Dyspnea Index (TDI) Focal Score After 26 Weeks of Treatment. | 1.34 ± 3.440 | 0.87 ± 3.439 |
The percent of participants with at least one moderate exacerbation within the 26 weeks that required systemic corticosteroids and/or antibiotics during the treatment
| Percent of participants | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Percent of Participants With at Least One Exacerbation Requiring Systemic Corticosteroids and/or Antibiotics Over 26 Weeks | 10.9 | 13.3 |
The percent of patients with at least one severe exacerbation within the 26 weeks that required hospitalization. COPD exacerbations were considered to be severe if hospitalization were required.
| Percent of participants | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Percent of Participants With at Least One Exacerbation Requiring Hospitalization | 2.1 | 2.4 |
The number of participants with at least one moderate or severe COPD exacerbation. COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required.
| Participants | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Time- Event Analysis, Number of Participants With at Least One COPD Exacerbation (Moderate or Severe) During the Treatment Period | 62 | 70 |
Trough FEV1 is the mean value of FEV1 (forced expiratory volume in one second) measured at 23:15h and 23:45h after the morning doses. The baseline value was measured at day 1 prior to the first dose.
| Liters | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Baseline | 1.329 ± 0.4806 | 1.313 ± 0.4525 |
| Week 26 | 1.495 ± 0.5060 | 1.409 ± 0.4878 |
FEV1 30min is the forced expiratory volume in one second measured 30 min after the morning dose.
| Liters | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Baseline (n=475,458) | 1.517 ± 0.5025 | 1.495 ± 0.4860 |
| Week 26 (n=476,458) | 1.605 ± 0.5356 | 1.565 ± 0.5124 |
Part I of the SGRQ-C covers "symptoms" and is concerned with respiratory symptoms, their frequency and severity. Each questionnaire response has a unique empirically derived "weight". A score was calculated from these weights. The lowest possible value is zero and the highest 100. A higher value corresponds to greater impairment of health status.
| Score on a scale | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| Baseline (n=473,457) | 64.10 ± 19.884 | 64.29 ± 19.768 |
| Week 26 (n=476,458) | 58.31 ± 21.764 | 60.16 ± 20.678 |
Non-serious events are listed at a 3% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | — | 30/476 (6.3%) | 72/476 (15.1%) |
| Tiotropium Plus Formoterol and Placebo to QVA149 | — | 24/458 (5.2%) | 79/458 (17.2%) |
| Event | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| PneumoniaInfections and infestations | 0/476 | 4/458 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/476 | 3/458 |
| Myocardial infarctionCardiac disorders | 3/476 | 1/458 |
| Rib fractureInjury, poisoning and procedural complications | 2/476 | 0/458 |
| Intervertebral disc protrusionMusculoskeletal and connective tissue disorders | 2/476 | 0/458 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 2/476 | 1/458 |
| Atrial flutterCardiac disorders | 0/476 | 1/458 |
| Cardiac arrestCardiac disorders | 0/476 | 1/458 |
| Stress cardiomyopathyCardiac disorders | 0/476 | 1/458 |
| DiplopiaEye disorders | 0/476 | 1/458 |
| Event | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 |
|---|---|---|
| NasopharyngitisInfections and infestations | 42/476 | 53/458 |
| CoughRespiratory, thoracic and mediastinal disorders | 26/476 | 20/458 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 9/476 | 15/458 |
| Age, Continuous(Years) | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 | Total |
|---|---|---|---|
| Mean | 62.6 ± 8.43 | 63.1 ± 8.15 | 62.9 ± 8.29 |
| Sex: Female, Male(Participants) | QVA149 Plus Placebo to Tiotropium and Placebo to Formoterol | Tiotropium Plus Formoterol and Placebo to QVA149 | Total |
|---|---|---|---|
| Female | 159 | 160 | 319 |
| Male | 317 | 298 | 615 |
Showing the first 100 of 144 sites.
This study is completed, as verified in May 2014. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Indacaterol-glycopyrronium combination
Pulmonary Disease, Chronic Obstructive →