Comparison of Safety and Efficacy of the Combination Product QVA149A Against the Concurrent Administration of the Individual Components, QAB149 and NVA237, in Patients With Chronic Obstructive Pulmonary Disease (COPD) (BEACON)
This study has been completed.
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01529632
First received: February 6, 2012
Last updated: May 21, 2013
Last verified: May 2013
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Purpose
The study will assess the safety and efficacy of the fixed combination product QVA149 versus the component products QAB149 and NVA237, administered concurrently, in patients that have moderate to severe chronic obstructive pulmonary disease (COPD).
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Obstructive Pulmonary Disease |
Drug: QVA149 Drug: NVA237 Drug: QAB149 Drug: Placebo |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| Official Title: | A Study to Compare the Efficacy and Safety of Once Daily QVA149 Versus the Once Daily Concurrent Administration of QAB149 Plus NVA237 in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease |
Resource links provided by NLM:
Further study details as provided by Novartis:
Primary Outcome Measures:
- Trough Forced Expiratory Volume in 1 Second (FEV1) after 28 days of blinded treatment [ Time Frame: 28 days ] [ Designated as safety issue: No ]Spirometry will be conducted according to internationally accepted standards. Trough FEV1 is defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings. The mixed model will contain treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilator, FEV1 post inhalation of short acting bronchodilator as covariates. This model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.
Secondary Outcome Measures:
- Change From Baseline in the Mean Number of Puffs Per Day of Rescue Medication Over the Study Duration (Baseline to Day 28) [ Time Frame: 28 days ] [ Designated as safety issue: No ]Patients will record the number of puffs of rescue medication in the past 12 hours each morning and evening in the diary. The number of puffs per day during active treatment will be calculated and divided by the total number of days with non-missing data to derive the mean daily number of puffs. If the number of puffs is missing for part of the day then a half day will be used in the denominator. Rescue med use during run-in will be used as baseline. The mean change from baseline will be analyzed using the same MIXED model as primary analysis with baseline daily rescue use replacing FEV1.
- Change From Baseline in the Mean Number of Puffs of Rescue Medication During the Daytime and Nighttime Over the Study Duration (Baseline to Day 28) [ Time Frame: 28 days ] [ Designated as safety issue: No ]The daytime and nighttime rescue medication use in terms of number of puffs will be calculated in a similar way as for the daily rescue medication use. Change from baseline in the mean daytime and nighttime number of puffs of rescue medication will be analyzed as for the change from baseline in the mean daily number of puffs of rescue medication.
- Percentage of Days With No Puffs of Rescue Medication During the Daytime and Nighttime Over the Study Duration (Baseline to Day 28) [ Time Frame: 28 days ] [ Designated as safety issue: No ]A 'day with no rescue use' is defined from diary data as any day where the patient has taken no puffs of rescue medication. The percentage of 'days with no rescue use' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
- Percentage of Nights With no Nighttime Awakenings Over the 28 Day Treatment Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]A night with 'no nighttime awakenings' is defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the whole treatment period will be divided by the total number of nights where diary recordings have been made in order to derive the percentage nights with 'no nighttime awakenings'.
- Percentage of Days With no Daytime Symptoms Over the 28 Day Treatment Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]A day with 'no daytime symptoms' is defined from the diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours. However, a patient will not be considered symptom free if they have used rescue medication that day even if his/her total daytime symptoms score is zero. The percentage of days with 'no daytime symptoms' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
- Percentage of Days Able to Perform Usual Daily Activities Over the 28 Day Treatment Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]A 'day able to perform usual daily activities' is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The percentage of 'days able to perform usual daily activities' will be derived and analyzed as for the percentage of 'nights with no nighttime awakenings'.
- Mean Daily Total Symptom Score Over the 28 Day Treatment Period [ Time Frame: 28 days ] [ Designated as safety issue: No ]The mean total symptom scores and mean individual symptom scores for the patient will be calculated for the whole study period. Total score is based on diary entry with total daily score range of 0-54, with 54 being the maximum symptom score. The mean change from baseline in the total scores and in the individual scores will be summarized by treatment and will be analyzed as for the percentage of 'nights with no nighttime awakenings'.
- Number of Participants With Adverse Events, Death, and Serious or Clinically Significant Adverse Events or Related Discontinuations [ Time Frame: 28 days and 30 day follow-up period ] [ Designated as safety issue: Yes ]Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.
- Safety and tolerability [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Data from the ECGs will be summarized by treatment at all time. Vital signs (blood pressure and radial pulse rate) data will be summarized by treatment at 35 min pre-dose and 1 h post-dose time points at Visit 2, 3, and 5.
All lab data will be listed with abnormal values flagged. The lab values and the change from baseline for continuous lab parameters will be summarized at each visit. A frequency table of results for categorical lab parameters will be produced by visit. Shift tables relative to normal ranges will be used to summarize the change from baseline to post-baseline by visit.
- FEV1 AUC 0-4h at Day 1 and Day 28 [ Time Frame: Day 1 and Day 28 ] [ Designated as safety issue: No ]Spirometry will be conducted according to internationally accepted standards. FEV1 was measured at 45 and 15 minutes pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, and at 23 h 15 min and 23 h 45 min post dose, by visit. The mixed model will contain treatment as a fixed effect with the baseline measurement of trough FEV1, FEV1 prior to inhalation of short acting bronchodilator, FEV1 post inhalation of short acting bronchodilator as covariates. This model will also include smoking status at baseline (current/ex-smoker), history of ICS use as fixed effects and center as a random effect.
| Enrollment: | 195 |
| Study Start Date: | May 2012 |
| Study Completion Date: | December 2012 |
| Primary Completion Date: | December 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: QVA149
QVA149 110/50µg plus placebo once daily delivered via the single dose dry powder inhaler (SDDPI) for 28 days.
|
Drug: QVA149
QVA149 110/50 ug will be supplied as capsules in blister packs
Drug: Placebo
Placebo capsules will match the appearance of NVA/QAB capsules and be provided in blister packs
|
|
Active Comparator: indacaterol (QAB149) plus glycopyrronium bromide (NVA237)
Indacaterol (QAB149) 150µg plus glycopyrronium bromide (NVA237) 50µg once daily delivered via the single dose dry powder inhaler (SDDPI) for 28 days.
|
Drug: NVA237
NVA237 50 ug will be supplied as capsules in blister packs
Drug: QAB149
QAB149 150 ug will be supplied as capsules in blister packs
|
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Male or female adults aged ≥ 40 yrs
- Smoking history of at least 10 pack years
- Diagnosis of COPD (moderate to severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2010)
- Post-bronchodilator FEV1 < 80% and ≥ 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) < 70%
Exclusion Criteria:
- Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1
- Patients with concomitant pulmonary disease
- Patients with a history of asthma
- Any patient with lung cancer or a history of lung cancer
- Patients with a history of certain cardiovascular co-morbid conditions
- Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency
- Patients in the active phase of a supervised pulmonary rehabilitation program
- Patients contraindicated for inhaled anticholinergic agents and β2 agonists
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01529632
Locations
| Austria | |
| Novartis Investigative Site | |
| Feldbach, Austria, 8330 | |
| Novartis Investigative Site | |
| Grieskirchen, Austria, 4710 | |
| Novartis Investigative Site | |
| Linz, Austria, 4020 | |
| Novartis Investigative Site | |
| Wels, Austria, 4600 | |
| Denmark | |
| Novartis Investigative Site | |
| Aalborg, Denmark, DK-9100 | |
| Novartis Investigative Site | |
| Copenhagen NV, Denmark, DK-2400 | |
| Novartis Investigative Site | |
| Hvidovre, Denmark, DK-2650 | |
| Novartis Investigative Site | |
| Odense C, Denmark, DK-5000 | |
| Novartis Investigative Site | |
| Århus, Denmark, DK-8000 | |
| Netherlands | |
| Novartis Investigative Site | |
| Almelo, Netherlands, 7609 PP | |
| Novartis Investigative Site | |
| Eindhoven, Netherlands, 5623 EJ | |
| Novartis Investigative Site | |
| Harderwijk, Netherlands, 3840 AC | |
| Novartis Investigative Site | |
| Heerlen, Netherlands, 6419 PC | |
| Novartis Investigative Site | |
| Hengelo, Netherlands, 7555 DL | |
| Novartis Investigative Site | |
| Sittard-Geleen, Netherlands, 6162 BG | |
| Novartis Investigative Site | |
| Tubbergen, Netherlands, 7651 JH | |
| Novartis Investigative Site | |
| Veldhoven, Netherlands, 5504 DB | |
| Norway | |
| Novartis Investigative Site | |
| Kløfta, Norway, 2040 | |
| Novartis Investigative Site | |
| Kongsvinger, Norway, 2212 | |
| Novartis Investigative Site | |
| Skedsmokorset, Norway, 2020 | |
| Novartis Investigative Site | |
| Stavanger, Norway, 4005 | |
| Novartis Investigative Site | |
| Trondheim, Norway, 7006 | |
| Sweden | |
| Novartis Investigative Site | |
| Göteborg, Sweden, 412 63 | |
| Novartis Investigative Site | |
| Stockholm, Sweden, S-171 76 | |
| Novartis Investigative Site | |
| Stockholm, Sweden, 111 57 | |
| Novartis Investigative Site | |
| Uddevalla, Sweden, 451 50 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT01529632 History of Changes |
| Other Study ID Numbers: | CQVA149A2326, 2011-006050-91 |
| Study First Received: | February 6, 2012 |
| Last Updated: | May 21, 2013 |
| Health Authority: | United States: Food and Drug Administration Austria: Agency for Health and Food Safety Denmark: Danish Medicines Agency Netherlands: Medicines Evaluation Board (MEB) Norway: Norwegian Medicines Agency Sweden: Medical Products Agency |
Keywords provided by Novartis:
|
chronic obstructive pulmonary disease COPD QVA149 QAB149 |
NVA237 indacaterol glycopyrronium bromide |
Additional relevant MeSH terms:
|
Lung Diseases Respiration Disorders Pulmonary Disease, Chronic Obstructive Lung Diseases, Obstructive Respiratory Tract Diseases Glycopyrrolate Adjuvants, Anesthesia Central Nervous System Agents |
Therapeutic Uses Pharmacologic Actions Muscarinic Antagonists Cholinergic Antagonists Cholinergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 21, 2013