Efficacy and Safety of QMF149 vs. Salmeterol Xinafoate/Fluticasone Propionate in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01636076
Collaborator
(none)
629
116
2
10
5.4
0.5
Study Details
Study Description
Brief Summary
To compare the efficacy, safety and pharmacokinetics of QMF149 delivered via Concept1 to salmeterol xinafoate/fluticasone propionate delivered via Accuhaler in adult patients with COPD
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
629 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, 12-week Treatment, Parallel-group Study to Evaluate the Efficacy and Safety of QMF149 (150 µg/160 µg o.d.) Compared With Salmeterol Xinafoate/Fluticasone Propionate (50 µg/500 µg b.i.d.) in Patients With Chronic Obstructive Pulmonary Disease
Study Start Date
:
Nov 1, 2012
Actual Primary Completion Date
:
Sep 1, 2013
Actual Study Completion Date
:
Sep 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: QMF149 QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device |
Drug: QMF149
delivered via Concept1 device
|
| Active Comparator: Salmeterol xinafoate/fluticasone propionate Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
Drug: Salmeterol
delivered via Accuhaler®
|
Outcome Measures
Primary Outcome Measures
- Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for Trough FEV1 (L) on Day 85 [12 weeks]
Spirometry is conducted according to the global standard. Trough FEV1 is defined as the average of the 23 hour 10 minute and 23 hour 45 minute post dose FEV1 readings.
Secondary Outcome Measures
- Trough FEV1 After First Dose and After 4 Weeks of Treatment [Day 1 and Day 85]
Spirometry is conducted according to the global standard. FEV1 is measured at pre-dose and post dose up to 1 hours on Day 1 and Day 28; 24 hours post-dose on Day 29 and 85. In a subset of approximately 60 patients, FEV1 is measured up to 20 hours postdose on Day 28 and Day 84.
- Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint [Day 1 through day 85]
- Forced Vital Capacity (FVC) at Each Timepoint [Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85]
Spirometry is conducted according to the global standard. FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84.
- FEV1/FVC at Each Timepoint [Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85]
Spirometry is conducted according to the global standard. FEV1/FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84.
- FEV1 (L) on Day 1 Between-treatment Comparisons of AUC (5min - 4h) [Day 1]
Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), Scheduled (not actual) time points are to be used. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment.
- FEV1 AUC (5 Min-4 h), [Day 1(Baseline), Day 28, Day 84]
Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), (5 min-24 h) is measured after the first dose on Day 1 and on Day 28 and Day 84 in a subset of approximately 60 patients. Scheduled (not actual) time points are to be used. The interpretation of FEV1 at time 0 is the baseline value at the randomization visit and the latest pre-dose value (-50 min or -15 min) at subsequent visits. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. The same will be repeated for standardized AUC for FEV1 between 5 min and 24 hours post morning dose.
- Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for AUC (5 Min - 23 h 45 Min) for FEV1 (L) on Day 28 and Day 84 (Full Analysis Set, 24-h Profiling Subgroup) [Day 28, Day 84]
Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), (5 min-24 h) is measured after the first dose on Day 1 and on Day 28 and Day 84 in a subset of approximately 60 patients. Scheduled (not actual) time points are to be used. The interpretation of FEV1 at time 0 is the baseline value at the randomization visit and the latest pre-dose value (-50 min or -15 min) at subsequent visits. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. The same will be repeated for standardized AUC for FEV1 between 5 min and 24 hours post morning dose.
- The Usage of Rescue Medication (Short Acting β2-agonist) [12 weeks]
Participants record the number of puffs of rescue medication taken in the previous 12 hours each morning and evening throughout the 12 week treatment period.
- The Overall Change in Usage of Rescue Medication (Short Acting β2-agonist) . [Baseline to 12 weeks]
This value represents the percent of days in the study where no rescue medication was needed.
- Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) [4 and 12 weeks]
A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.
- Analysis of the Proportion of Subjects With a Clinically Important Improvement of >=1 Point in the TDI (Transitional Dyspnoea Index)Focal Score by Visit [4 and 12 weeks]
A TDI focal score of ≥1 is considered to be a clinically important improvement from baseline. Analysis of the proportion of subjects with a clinically important improvement of >=1 point in the TDI focal score, by visit
- Patient Reported Outcome Measures: COPD Assessment Test [Baseline, 4 and 12 weeks]
It consists of eight items, each presented as a semantic 6-point differential scale, providing a total score out of 40. A higher score indicates a worse health status. Scores of 0 - 10, 11 - 20, 21 - 30 and 31 - 40 represent a mild, moderate, severe or very severe clinical impact of COPD upon the patient.
- Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale [Baseline, 4 and 12 weeks]
Scoring the MOS Sleep Survey is a two-step process:• All items are scored so that a high score reflects more of the attribute implied by the scale name. Each item is converted to a 0 to 100 possible range so that the lowest and highest possible scores are set at 0 and 100, respectively. In this format, scores represent the achieved percentage of the total possible score. For example, a score of 50 represents 50% of the highest possible score. • Second, items within each scale are averaged together to create the 7 scale scores. Scales with at least one item answered can be used to generate a scale score. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Scores represent the average for all items in the scale that the respondent answered. An additional measure is based on the average number of hours sleep each night during the past 4 weeks and are described in outcome measure 15.
- Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale [Baseline, 4 and 12 weeks]
The sleep quantity subscale,which refers to question 2 of the PRO: On average, how many hours did you sleep each night during the past 4 weeks. More hours of sleep indicate better outcome.
- Summary Statistics of COPD Exacerbations over12 Weeks as Defined by Chronic Pulmonary Disease Tool (EXACT) [12 weeks]
The EXACT is a 14-item electronic questionnaire designed to detect the frequency, severity, and duration of exacerbations in patients with COPD.
- Time to First COPD Exacerbation [12 weeks]
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. The reported measure will detail the percentage of participants that were event free of a specified event.
- Annual Rate of COPD Exacerbations [12 weeks]
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.
- Duration (in Days) of COPD Exacerbations [12 weeks]
Duration and number of the COPD exacerbation will be analyzed by the negative binomial regression model including treatment, country, smoking status, and COPD severity as factors and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.
- Percentage of Patients With at Least One Exacerbation up to Week 12 [12 weeks]
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. The reported measure will detail the percentage of participants that had an exacerbation up to week 12. Less exacerbations reflect a better outcome.
- Time (in Days) to Permanent Study Discontinuation Due to COPD Exacerbation [12 weeks]
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.
- The Percentage of Patients Who Permanently Discontinued Due to COPD Exacerbation [12 weeks]
Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates.
- Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period [12 weeks]
Total amount (in doses) of systemic corticosteroid used to treat COPD exacerbation will be summarized descriptively by treatment group per each systemic corticosteroid.
- Plasma Cortisol Concentrations at Each Timepoint [Day 1, Day 28, Day 84]
Plasma cortisol to be measured in a subset of approximately 60 patients via central laboratory. Blood sample for Plasma cortisol is collected at pre-dose and post dose up to 4 hour on Day 1, up to 12 hours post-dose on Day 28 and Day 84, and 23 hour 35 minute on Day 2, Day 29, and Day 85, and at pre-dose 25 minute on Day 28, and Day 84.
- Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint [Day 1, 29, 84]
Plasma indacaterol and mometasone furoate is to be measured in a subset of approximately 60 patients via central laboratory. Blood samples are collected at pre-dose on Day 1, 29, and 84; and post dose up to 4 hour on Day 1, up to 12 hours on Day 28 and 84. For sparse pharmacokinetic testing, blood samples will be collected at 23h 35 min post-dose following morning dose administration on Day 28 and 84, in all patients participating in this study.
- Pharmacokinetic Parameter: Cmax [Day 28, 84]
Maximum observed plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.
- Pharmacokinetic Parameter--Tmax [Day 28, 84]
Time to reach the maximum plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.
- Pharmacokinetic Parameter--AUC0-t [Day 28, 84]
Area under the plasma concentration time curve from time zero to time "t" post-dose is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Patients with moderate to very severe COPD (GOLD 2 to GOLD 4) according to the 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines
-
Patients with a post-bronchodilator FEV1 < 70% of the predicted normal, and a post-bronchodilator FEV1/FVC < 0.70 at run-in (Visit 101).
-
Current or ex-smokers who have a smoking history of at least 10 pack years (defined as the number of packs of 20 cigarettes smoked per day multiplied by number of years the patient smoked. e.g.10 pack years = 1 pack /day x 10 yrs, or ½ pack/day x 20 yrs). An ex-smoker may be defined as a subject who has not smoked for ≥ 6 months at screening.
Exclusion Criteria:
-
Patients who have had a COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the 6 weeks prior to screening (Visit 1).
-
Patients who develop a COPD exacerbation between screening (Visit 1) and treatment (Visit 201) will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.
-
Patients who have had a respiratory tract infection within 4 weeks prior to screening Visit 1.
-
Patients who develop a respiratory tract infection between screening (Visit 1) and treatment (Visit 201) will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection.
-
Patients requiring long term oxygen therapy prescribed for >12 hours per day.
-
Patients with, a) any history of asthma or, b) onset of respiratory symptoms prior to age 40 years.
Other protocol-defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Concord | New South Wales | Australia | 2139 |
| 2 | Novartis Investigative Site | Kogarah | New South Wales | Australia | 2217 |
| 3 | Novartis Investigative Site | New Lambton Heights | New South Wales | Australia | 2305 |
| 4 | Novartis Investigative Site | Redcliffe | Queensland | Australia | 4020 |
| 5 | Novartis Investigative Site | Bedford Park | South Australia | Australia | 5042 |
| 6 | Novartis Investigative Site | Daw Park | South Australia | Australia | 5041 |
| 7 | Novartis Investigative Site | Woodville South | South Australia | Australia | 5011 |
| 8 | Novartis Investigative Site | Box Hill | Victoria | Australia | 3128 |
| 9 | Novartis Investigative Site | Fitzroy | Victoria | Australia | 3065 |
| 10 | Novartis Investigative Site | Franston | Victoria | Australia | 3199 |
| 11 | Novartis Investigative Site | Nedlands | Western Australia | Australia | 6009 |
| 12 | Novartis Investigative Site | Bruxelles | Belgium | 1000 | |
| 13 | Novartis Investigative Site | Halen | Belgium | 3545 | |
| 14 | Novartis Investigative Site | Liege | Belgium | 4000 | |
| 15 | Novartis Investigative Site | Pleven | Bulgaria | 5800 | |
| 16 | Novartis Investigative Site | Russe | Bulgaria | 7002 | |
| 17 | Novartis Investigative Site | Sofia | Bulgaria | 1233 | |
| 18 | Novartis Investigative Site | Sofia | Bulgaria | 1234 | |
| 19 | Novartis Investigative Site | Sofia | Bulgaria | 1431 | |
| 20 | Novartis Investigative Site | Stara Zagora | Bulgaria | 6000 | |
| 21 | Novartis Investigative Site | Varna | Bulgaria | 9010 | |
| 22 | Novartis Investigative Site | Veliko Tarnovo | Bulgaria | 5000 | |
| 23 | Novartis Investigative Site | Copenhagen NV | Denmark | DK-2400 | |
| 24 | Novartis Investigative Site | Hellerup | Denmark | DK-2900 | |
| 25 | Novartis Investigative Site | Hvidovre | Denmark | DK-2650 | |
| 26 | Novartis Investigative Site | Odense C | Denmark | DK-5000 | |
| 27 | Novartis Investigative Site | Pori | Finland | FIN-28500 | |
| 28 | Novartis Investigative Site | Tampere | Finland | FIN-33521 | |
| 29 | Novartis Investigative Site | Turku | Finland | FIN-20100 | |
| 30 | Novartis Investigative Site | Berlin | Germany | 10969 | |
| 31 | Novartis Investigative Site | Berlin | Germany | 12203 | |
| 32 | Novartis Investigative Site | Donaustauf | Germany | 93093 | |
| 33 | Novartis Investigative Site | Frankfurt | Germany | 60596 | |
| 34 | Novartis Investigative Site | Großhansdorf | Germany | 22927 | |
| 35 | Novartis Investigative Site | Hannover | Germany | 30167 | |
| 36 | Novartis Investigative Site | Lübeck | Germany | 23552 | |
| 37 | Novartis Investigative Site | Rüdersdorf | Germany | 15562 | |
| 38 | Novartis Investigative Site | Wiesbaden | Germany | 65187 | |
| 39 | Novartis Investigative Site | Witten | Germany | 58452 | |
| 40 | Novartis Investigative Site | Heraklion Crete | Crete | Greece | GR-71110 |
| 41 | Novartis Investigative Site | Athens - GR | Greece | 10676 | |
| 42 | Novartis Investigative Site | Athens | Greece | 11527 | |
| 43 | Novartis Investigative Site | Athens | Greece | GR 115 27 | |
| 44 | Novartis Investigative Site | Athens | Greece | GR-106 76 | |
| 45 | Novartis Investigative Site | Larissa | Greece | GR 41110 | |
| 46 | Novartis Investigative Site | Thessaloniki | Greece | GR 56403 | |
| 47 | Novartis Investigative Site | Thessaloniki | Greece | GR 570 10 | |
| 48 | Novartis Investigative Site | Hong Kong | Hong Kong | ||
| 49 | Novartis Investigative Site | New Territories | Hong Kong | ||
| 50 | Novartis Investigative Site | Balasagyarmat | Hungary | 2660 | |
| 51 | Novartis Investigative Site | Budapest | Hungary | 1036 | |
| 52 | Novartis Investigative Site | Farkasgyepu | Hungary | 8582 | |
| 53 | Novartis Investigative Site | Kapuvár | Hungary | 9330 | |
| 54 | Novartis Investigative Site | Nyiregyhaza | Hungary | 4400 | |
| 55 | Novartis Investigative Site | Pécs | Hungary | 7633 | |
| 56 | Novartis Investigative Site | Siofok | Hungary | 8600 | |
| 57 | Novartis Investigative Site | Sopron | Hungary | H-9401 | |
| 58 | Novartis Investigative Site | Szarvas | Hungary | 5540 | |
| 59 | Novartis Investigative Site | Veszprém | Hungary | 8200 | |
| 60 | Novartis Investigative Site | Ashkelon | Israel | 78278 | |
| 61 | Novartis Investigative Site | Haifa | Israel | 34362 | |
| 62 | Novartis Investigative Site | Jerusalem | Israel | 91031 | |
| 63 | Novartis Investigative Site | Jerusalem | Israel | 91120 | |
| 64 | Novartis Investigative Site | Kfar-Sava | Israel | 44281 | |
| 65 | Novartis Investigative Site | Petach Tikva | Israel | 49100 | |
| 66 | Novartis Investigative Site | Rehovot | Israel | 76100 | |
| 67 | Novartis Investigative Site | Tel-Aviv | Israel | 64239 | |
| 68 | Novartis Investigative Site | Batu Caves | Malaysia | 68100 | |
| 69 | Novartis Investigative Site | Kuala Lumpur | Malaysia | 59100 | |
| 70 | Novartis Investigative Site | Taiping | Malaysia | 34000 | |
| 71 | Novartis Investigative Site | Bialystok | Poland | 15-010 | |
| 72 | Novartis Investigative Site | Bialystok | Poland | 15-270 | |
| 73 | Novartis Investigative Site | Bialystok | Poland | 15-461 | |
| 74 | Novartis Investigative Site | Gdansk | Poland | 80-211 | |
| 75 | Novartis Investigative Site | Ilawa | Poland | 14-200 | |
| 76 | Novartis Investigative Site | Katowice | Poland | 40-752 | |
| 77 | Novartis Investigative Site | Lodz | Poland | 90-153 | |
| 78 | Novartis Investigative Site | Ostrow Wielkopolski | Poland | 63-400 | |
| 79 | Novartis Investigative Site | Pila | Poland | 64-920 | |
| 80 | Novartis Investigative Site | Poznan | Poland | 60-569 | |
| 81 | Novartis Investigative Site | Szczecin | Poland | 71-124 | |
| 82 | Novartis Investigative Site | Tarnow | Poland | 33-100 | |
| 83 | Novartis Investigative Site | Wroclaw | Poland | 50-434 | |
| 84 | Novartis Investigative Site | Constanta | Jud. Constanta | Romania | 900002 |
| 85 | Novartis Investigative Site | Bucharest | Romania | 020125 | |
| 86 | Novartis Investigative Site | Bucuresti | Romania | 50159 | |
| 87 | Novartis Investigative Site | Cluj Napoca | Romania | 400162 | |
| 88 | Novartis Investigative Site | Cluj-Napoca | Romania | 400371 | |
| 89 | Novartis Investigative Site | Targu Mures | Romania | 540136 | |
| 90 | Novartis Investigative Site | Targu-Mures | Romania | 540136 | |
| 91 | Novartis Investigative Site | Singapore | Singapore | 119074 | |
| 92 | Novartis Investigative Site | Singapore | Singapore | 169608 | |
| 93 | Novartis Investigative Site | Johannesburg | Gauteng | South Africa | 2057 |
| 94 | Novartis Investigative Site | Bloemfontein | South Africa | 9301 | |
| 95 | Novartis Investigative Site | Cape Town | South Africa | 7500 | |
| 96 | Novartis Investigative Site | Cape Town | South Africa | 7505 | |
| 97 | Novartis Investigative Site | Cape Town | South Africa | 7531 | |
| 98 | Novartis Investigative Site | Cape Town | South Africa | 7764 | |
| 99 | Novartis Investigative Site | Cape Town | South Africa | 7925 | |
| 100 | Novartis Investigative Site | Durban | South Africa | 4001 | |
| 101 | Novartis Investigative Site | Umkomaas | South Africa | 4170 | |
| 102 | Novartis Investigative Site | Barcelona | Cataluña | Spain | 08025 |
| 103 | Novartis Investigative Site | Barcelona | Cataluña | Spain | 08035 |
| 104 | Novartis Investigative Site | Valencia | Comunidad Valenciana | Spain | 46015 |
| 105 | Novartis Investigative Site | Palma De Mallorca | Islas Baleares | Spain | 07120 |
| 106 | Novartis Investigative Site | Göteborg | Sweden | 405 30 | |
| 107 | Novartis Investigative Site | Göteborg | Sweden | 412 63 | |
| 108 | Novartis Investigative Site | Lund | Sweden | SE-221 85 | |
| 109 | Novartis Investigative Site | Malmö | Sweden | 21152 | |
| 110 | Novartis Investigative Site | Vällingby | Sweden | 162 68 | |
| 111 | Novartis Investigative Site | Taladkwan | Nonthaburi | Thailand | 11000 |
| 112 | Novartis Investigative Site | Bangkok | Thailand | 10400 | |
| 113 | Novartis Investigative Site | Bangkok | Thailand | 10700 | |
| 114 | Novartis Investigative Site | Muang | Thailand | 40002 | |
| 115 | Novartis Investigative Site | Nakhon Naiyok | Thailand | 26120 | |
| 116 | Novartis Investigative Site | Songkla | Thailand | 90110 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01636076
Other Study ID Numbers:
- CQMF149F2202
- 2012-001172-12
First Posted:
Jul 10, 2012
Last Update Posted:
Nov 17, 2014
Last Verified:
Nov 1, 2014
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Period Title: Overall Study | ||
| STARTED | 316 | 313 |
| COMPLETED | 299 | 288 |
| NOT COMPLETED | 17 | 25 |
Baseline Characteristics
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate | Total |
|---|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® | Total of all reporting groups |
| Overall Participants | 316 | 313 | 629 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
64.8
(7.74)
|
64.1
(7.89)
|
64.5
(7.82)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
83
26.3%
|
86
27.5%
|
169
26.9%
|
| Male |
233
73.7%
|
227
72.5%
|
460
73.1%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
32
10.1%
|
30
9.6%
|
62
9.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
0.3%
|
1
0.3%
|
2
0.3%
|
| White |
273
86.4%
|
276
88.2%
|
549
87.3%
|
| Other |
9
2.8%
|
6
1.9%
|
15
2.4%
|
| Unknown or Not Reported |
1
0.3%
|
0
0%
|
1
0.2%
|
Outcome Measures
| Title | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for Trough FEV1 (L) on Day 85 |
|---|---|
| Description | Spirometry is conducted according to the global standard. Trough FEV1 is defined as the average of the 23 hour 10 minute and 23 hour 45 minute post dose FEV1 readings. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized patients were included in the Full analysis set (FAS) |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Full analysis set (n=291,282) |
1.270
(0.0124)
|
1.215
(0.0124)
|
| Per protocol set (n=259,251) |
1.277
(0.0136)
|
1.228
(0.0137)
|
| Title | Trough FEV1 After First Dose and After 4 Weeks of Treatment |
|---|---|
| Description | Spirometry is conducted according to the global standard. FEV1 is measured at pre-dose and post dose up to 1 hours on Day 1 and Day 28; 24 hours post-dose on Day 29 and 85. In a subset of approximately 60 patients, FEV1 is measured up to 20 hours postdose on Day 28 and Day 84. |
| Time Frame | Day 1 and Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All randomized patients were included in the Safety analysis set (SAF) and Full analysis set (FAS). |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Baseline Day 2 (n=286, 302) |
1.147
(0.0237)
|
1.167
(0.0264)
|
| Day 2 (n=286, 302) |
1.216
(0.0106)
|
1.243
(0.0104)
|
| Baseline Day 29 (n=293, 296) |
1.148
(0.0236)
|
1.178
(0.0266)
|
| Day 29 (n=293,296) |
1.277
(0.0119)
|
1.247
(0.0119)
|
| Day 84 baseline (n=289,287) |
1.144
(0.0240)
|
1.187
(0.0267)
|
| Day 84 (n=289,287) |
1.269
(0.0139)
|
1.208
(0.0139)
|
| Title | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for FEV1 (L), by Visit and Timepoint |
|---|---|
| Description | |
| Time Frame | Day 1 through day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Absolute Value Day 1/5min (n=290,298) |
1.254
(0.0069)
|
1.198
(0.0068)
|
| Absolute Value Day 1/30 min (n=294,306) |
1.281
(0.0079)
|
1.250
(0.0087)
|
| Absolute Value Day 1/60min (n=300,303) |
1.281
(0.0087)
|
1.256
(0.0087)
|
| Absolute Value Day 2/ 23 hr 10 min (n=288,295) |
1.213
(0.0108)
|
1.239
(0.0107)
|
| Absolute Value Day 2/ 23 hr 45 min (n=297,305) |
1.215
(0.0106)
|
1.244
(0.0105)
|
| Absolute Value Day 28/ -50min (n=288,295) |
1.265
(0.0132)
|
1.287
(0.0139)
|
| Absolute Value Day 28/ -15min (n=292,290) |
1.287
(0.0132)
|
1.235
(0.0140)
|
| Absolute Value Day 28/ 5min (n=290,289) |
1.329
(0.0113)
|
1.268
(0.0113)
|
| Absolute Value Day 28/ 30min (n=293,290) |
1.352
(0.0118)
|
1.298
(0.0118)
|
| Absolute Value Day 28/ 60min (n=292,290) |
1.353
(0.0123)
|
1.298
(0.0122)
|
| Absolute Value Day 29/ 23 hr 10 min (n=285,292) |
1.269
(0.0118)
|
1.242
(0.0117)
|
| Absolute Value Day 29/ 23 hr 45 min (n=290,295) |
1.281
(0.0123)
|
1.254
(0.0122)
|
| Absolute Value Day 84/ -50 min (n=286,278) |
1.259
(0.0140)
|
1.195
(0.0141)
|
| Absolute Value Day 84/ -15 min (n=282,285) |
1.282
(0.0146)
|
1.222
(0.0147)
|
| Absolute Value Day 84/ 5 min (n=280,279) |
1.336
(0.0128)
|
1.243
(0.0128)
|
| Absolute Value Day 84/ 30 min (n=286,280) |
1.352
(0.0124)
|
1.277
(0.0124)
|
| Absolute Value Day 84/ 60 min (n=287,281) |
1.351
(0.0128)
|
1.283
(0.0128)
|
| Absolute Value Day 84/ 23 hr 10 min (n=292,291) |
1.264
(0.0125)
|
1.212
(0.0125)
|
| Absolute Value Day 84/ 23 hr 45 min (n=291,285) |
1.273
(0.0125)
|
1.221
(0.0126)
|
| Title | Forced Vital Capacity (FVC) at Each Timepoint |
|---|---|
| Description | Spirometry is conducted according to the global standard. FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84. |
| Time Frame | Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Baseline (n=316,313) |
2.460
(0.6969)
|
2.481
(0.7209)
|
| Day 1/ 5 min (n=299,298) Change |
0.179
(0.2165)
|
0.060
(0.1404)
|
| Day 1/ 30 min (n=302,306) Change |
0.207
(0.2279)
|
0.129
(0.1953)
|
| Day 1/ 60 min (n=308,303) Change |
0.222
(0.2472)
|
0.152
(0.2287)
|
| Day 1/ 4 hr (n=302,297) Change |
0.217
(0.2847)
|
0.183
(0.2611)
|
| Day 2/ 23hr 10 min (n=297,296) Change |
0.089
(0.2518)
|
0.092
(0.2896)
|
| Day 2/ 23hr 45 min (n=307,306) Change |
0.083
(0.2583)
|
0.092
(0.2815)
|
| Day 28 / -50 min (n=295,296) Change |
0.132
(0.2806)
|
0.068
(0.2814)
|
| Day 28 / -15 min (n=300,291) Change |
0.161
(0.3090)
|
0.072
(0.2892)
|
| Day 28 / 5 min (n=297,290) Change |
0.238
(0.3163)
|
0.122
(0.3068)
|
| Day 28 / 30 min (n=301,291) Change |
0.263
(0.3169)
|
0.168
(0.3166)
|
| Day 28 / 60 min (n=299,292) Change |
0.279
(0.3261)
|
0.189
(0.3350)
|
| Day 29 / 23hr 10 min (n=293,293) Change |
0.121
(0.2955)
|
0.084
(0.2817)
|
| Day 29 /23hr 45 min (n=299,296) Change |
0.133
(0.3132)
|
0.097
(0.2965)
|
| Day 84 / -50min (n=295,279) Change |
0.125
(0.2979)
|
0.144
(0.3570)
|
| Day 84 /-15 min (n=291,286) Change |
0.144
(0.3234)
|
0.049
(0.3519)
|
| Day 84 / 5 min (n=288,290) Change |
0.229
(0.3370)
|
0.076
(0.3729)
|
| Day 84 /30 min (n=295,281) Change |
0.255
(0.3344)
|
0.120
(0.3537)
|
| Day 84 / 60 min (n=296,282) Change |
0.272
(0.3295)
|
0.159
(0.3648)
|
| Day 85 / 23 hr 10 min (n=302,292) Change |
0.113
(0.3132)
|
0.022
(0.3482)
|
| Day 85 / 23 hr 45 min (n=301,286) Change |
0.126
(0.3206)
|
0.035
(0.3620)
|
| Title | FEV1/FVC at Each Timepoint |
|---|---|
| Description | Spirometry is conducted according to the global standard. FEV1/FVC is measured at pre-dose and post dose up to 4 hour on Day 1, Day 28, and Day 84, at post dose 12 hour, 23 hour 10 minute and 23 hour 45 minutes on Day 2 and Day 29, and at pre-dose 50 min and 15 min on Day 2, Day 28, and Day 84. |
| Time Frame | Day 1, Day 2, Day 28, Day , Day 29, Day 84, Day 85 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Baseline (n=316, 313) |
46.786
(10.0306)
|
46.859
(10.0392)
|
| Day 1 / 5 min (n=299, 298) change |
0.488
(2.9633)
|
0.047
(2.1366)
|
| Day 1 / 30 min (n=302,306) change |
0.955
(3.0166)
|
0.879
(2.7281)
|
| Day 1 / 60 min (n=308,303) change |
1.112
(3.1413)
|
1.182
(3.0612)
|
| Day 1 / 4 hr (n=302, 297) change |
1.045
(3.3917)
|
1.397
(3.2407)
|
| Day 2 / 23 Hr 10 min (n=297,296) change |
0.503
(3.3450)
|
1.042
(3.2074)
|
| Day 2 / 23 Hr 45 min (n=307,306) change |
0.583
(3.4552)
|
1.319
(3.1977)
|
| Day 28 / -50 min (n=295,296) change |
1.463
(3.7864)
|
1.140
(3.8900)
|
| Day 28 / -15 min (n=300,291) change |
1.837
(3.9769)
|
1.495
(3.7597)
|
| Day 28 / 5 min (n=297,290) change |
1.951
(4.0512)
|
1.581
(4.006)
|
| Day 28 / 30 min (n=301,291) change |
2.296
(4.4904)
|
1.873
(4.2723)
|
| Day 28 / 60 min (n=299,292) change |
2.525
(4.3228)
|
2.060
(4.4398)
|
| Day 28 / 4 hr (n=44,45) change |
4.034
(5.2622)
|
2.322
(4.0257)
|
| Day 28 / 11hr 10 min (n=47,44) change |
2.553
(4.0260)
|
1.909
(3.9389)
|
| Day 28 / 11hr 45 min (n=43,42) change |
2.791
(4.1708)
|
2.476
(4.3978)
|
| Day 28 / 16 hr (n=40,41) change |
2.250
(3.4006)
|
2.305
(4.3111)
|
| Day 28 / 20 hr (n=43,44) change |
2.535
(3.5379)
|
2.250
(3.9935)
|
| Day 29 / 23 hr 10 min (n=293,293) change |
1.771
(4.0730)
|
1.319
(3.8200)
|
| Day 29 / 23 hr 45 min (n=299,296) change |
2.000
(4.0562)
|
1.566
(3.9704)
|
| Day 84 / -50 min (n=295,279) change |
1.449
(4.1145)
|
1.068
(4.1776)
|
| Day 84 / -15 min (n=291,286) change |
2.155
(4.0673)
|
1.584
(4.3278)
|
| Day 84 / 5 min (n=288,280) change |
2.332
(4.1032)
|
1.796
(4.2310)
|
| Day 84 / 30 min (n=295,281) change |
2.420
(4.3561)
|
2.062
(4.3941)
|
| Day 84 / 60 min (n=296,282) change |
2.571
(4.4128)
|
2.067
(4.3512)
|
| Day 84 / 4 hr (n=45,44) change |
2.389
(3.7079)
|
2.682
(4.3269)
|
| Day 84 / 11hr 10 min (n=45,43) change |
1.944
(4.0833)
|
2.105
(3.8754)
|
| Day 84 / 11 hr 45 min (n=39,39) change |
2.538
(3.7895)
|
2.295
(4.1147)
|
| Day 84 / 16 hr (n=41,39) change |
1.415
(4.0588)
|
1.962
(3.6981)
|
| Day 84 / 20 hr (n=44,43) change |
2.364
(4.4315)
|
1.837
(3.7713)
|
| Day 84 / 23 hr 10 min (n=302,292) change |
1.856
(4.4315)
|
1.414
(4.0356)
|
| Day 84 / 23 hr 45 min (n=301,286) change |
2.098
(4.3676)
|
1.593
(4.2110)
|
| Title | FEV1 (L) on Day 1 Between-treatment Comparisons of AUC (5min - 4h) |
|---|---|
| Description | Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), Scheduled (not actual) time points are to be used. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. |
| Time Frame | Day 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Day 1 baseline (n=303,311) |
1.142
(0.0233)
|
1.169
(0.0259)
|
| Day 1 post (n=303,311) |
1.277
(0.0086)
|
1.260
(0.0085)
|
| Title | FEV1 AUC (5 Min-4 h), |
|---|---|
| Description | Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), (5 min-24 h) is measured after the first dose on Day 1 and on Day 28 and Day 84 in a subset of approximately 60 patients. Scheduled (not actual) time points are to be used. The interpretation of FEV1 at time 0 is the baseline value at the randomization visit and the latest pre-dose value (-50 min or -15 min) at subsequent visits. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. The same will be repeated for standardized AUC for FEV1 between 5 min and 24 hours post morning dose. |
| Time Frame | Day 1(Baseline), Day 28, Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 24 hr profiling subgroup |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 50 | 50 |
| Day 1 baseline (n=46,47) |
1.302
(0.0278)
|
1.331
(0.0282)
|
| Day 28 (n=45,46) |
1.410
(0.0353)
|
1.355
(0.0355)
|
| Day 84 (n=44,46) |
1.387
(0.0401)
|
1.372
(0.0401)
|
| Title | Mixed Model for Repeated Measures (MMRM): Between-treatment Comparisons for AUC (5 Min - 23 h 45 Min) for FEV1 (L) on Day 28 and Day 84 (Full Analysis Set, 24-h Profiling Subgroup) |
|---|---|
| Description | Spirometry is conducted according to the global standard. FEV1 AUC (5 min-4 h), (5 min-24 h) is measured after the first dose on Day 1 and on Day 28 and Day 84 in a subset of approximately 60 patients. Scheduled (not actual) time points are to be used. The interpretation of FEV1 at time 0 is the baseline value at the randomization visit and the latest pre-dose value (-50 min or -15 min) at subsequent visits. The standardized AUC(5 min - 4 h) for FEV1 will be summarized by treatment. The same will be repeated for standardized AUC for FEV1 between 5 min and 24 hours post morning dose. |
| Time Frame | Day 28, Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Peak FEV1 was calculated for all subjects in the FAS at Day 1 (Visit 201) and was calculated for all subjects in the 24-h profiling subset of the FAS at Day 1 (Visit 201), Day 28 (Visit 203) and Day 84 (Visit 205). |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 50 | 50 |
| Day 28 (n=45,46) |
1.352
(0.0428)
|
1.298
(0.0431)
|
| Day 85 (n=47,47) |
1.317
(0.0454)
|
1.303
(0.0459)
|
| Title | The Usage of Rescue Medication (Short Acting β2-agonist) |
|---|---|
| Description | Participants record the number of puffs of rescue medication taken in the previous 12 hours each morning and evening throughout the 12 week treatment period. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Daily Change Weeks 1-12 (n-281,274) |
-1.064
(0.1615)
|
-0.593
(0.1621)
|
| Daytime Change Weeks 1-12 (n=276-272) |
-0.625
(0.1021)
|
-0.300
(0.1026)
|
| Nighttime Change Weeks 1-12 (n=281,271) |
-0.452
(0.0748)
|
-0.308
(0.0751)
|
| Title | The Overall Change in Usage of Rescue Medication (Short Acting β2-agonist) . |
|---|---|
| Description | This value represents the percent of days in the study where no rescue medication was needed. |
| Time Frame | Baseline to 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Least Squares Mean (Standard Error) [% of days] |
8.796
(2.3845)
|
2.538
(2.3980)
|
| Title | Patient Reported Outcome Measures: SGRQ (St. George's Respiratory Questionnaire) |
|---|---|
| Description | A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present. |
| Time Frame | 4 and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set : At baseline all subjects with a baseline value are included. At each post-baseline day, only subjects with a value at both baseline and the respective day are included. Baseline SGRQ was completed on Day 1 prior to first dose. |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Baseline (n=314, 308) |
43.05
(18.515)
|
42.28
(17.941)
|
| Day 28 Baseline (n=304,295) |
42.87
(18.392)
|
42.47
(18.051)
|
| Day 28 Post (n=304,295) |
40.95
(18.527)
|
42.18
(18.101)
|
| Day 28 Change (n=304,295) |
-1.92
(11.383)
|
-0.29
(12.145)
|
| Day 84 Baseline (n=297,284) |
42.57
(18.322)
|
42.03
(18.099)
|
| Day 84 Post (n=297,284) |
39.81
(19.057)
|
41.01
(18.553)
|
| Day 84 Change (n=297,284) |
-2.76
(13.062)
|
-1.02
(12.178)
|
| Title | Analysis of the Proportion of Subjects With a Clinically Important Improvement of >=1 Point in the TDI (Transitional Dyspnoea Index)Focal Score by Visit |
|---|---|
| Description | A TDI focal score of ≥1 is considered to be a clinically important improvement from baseline. Analysis of the proportion of subjects with a clinically important improvement of >=1 point in the TDI focal score, by visit |
| Time Frame | 4 and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set, All randomized patients. When data were missing or insufficient for any one of the domains a focal score could not be calculated. |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Day 28 Change from baseline (n=291,294) |
43.3
(0.1314)
|
40.5
(0.1331)
|
| Day 84 Change from baseline (n=287,283) |
52.6
(0.1330)
|
45.9
(0.1390)
|
| Title | Patient Reported Outcome Measures: COPD Assessment Test |
|---|---|
| Description | It consists of eight items, each presented as a semantic 6-point differential scale, providing a total score out of 40. A higher score indicates a worse health status. Scores of 0 - 10, 11 - 20, 21 - 30 and 31 - 40 represent a mild, moderate, severe or very severe clinical impact of COPD upon the patient. |
| Time Frame | Baseline, 4 and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Baseline (n= 311,308) |
16.3
(7.60)
|
16.2
(7.48)
|
| Day 28 baseline (n=303,298) |
16.2
(7.58)
|
16.2
(7.48)
|
| Day 28 Post (n=303,298) |
15.8
(7.63)
|
16.8
(7.75)
|
| Day 28 Change (n=303,298) |
-0.4
(5.56)
|
0.6
(4.94)
|
| Day 84 Baseline (n=295,285) |
15.9
(7.54)
|
16.1
(8.38)
|
| Day 84 Post (n=295,285) |
15.5
(7.56)
|
16.3
(8.38)
|
| Day 84 change (n=295,285) |
-0.4
(5.77)
|
0.2
(5.84)
|
| Title | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Without Quantity Subscale |
|---|---|
| Description | Scoring the MOS Sleep Survey is a two-step process:• All items are scored so that a high score reflects more of the attribute implied by the scale name. Each item is converted to a 0 to 100 possible range so that the lowest and highest possible scores are set at 0 and 100, respectively. In this format, scores represent the achieved percentage of the total possible score. For example, a score of 50 represents 50% of the highest possible score. • Second, items within each scale are averaged together to create the 7 scale scores. Scales with at least one item answered can be used to generate a scale score. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Scores represent the average for all items in the scale that the respondent answered. An additional measure is based on the average number of hours sleep each night during the past 4 weeks and are described in outcome measure 15. |
| Time Frame | Baseline, 4 and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set. |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 302 | 296 |
| Sleep disturbance Day 28 Baseline (n=290,285) |
49.6833
(8.57069)
|
49.7616
(8.49307)
|
| Sleep disturbance Baseline (n=299,295) |
49.6423
(8.50059)
|
49.9292
(8.51330)
|
| Sleep disturbance Day 28 post (n=290,285) |
50.9323
(8.92540)
|
50.0858
(8.77110)
|
| Sleep disturbance Day 28 change (n=290,285) |
1.2490
(5.67591)
|
0.3242
(6.63156)
|
| Sleep disturbance Day 84 Baseline (n=283,274) |
49.7622
(8.61100)
|
49.6634
(8.41228)
|
| Sleep disturbance Day 84 Post (n=283,274) |
50.7508
(9.22016)
|
50.2380
(9.07204)
|
| Sleep disturbance Day 84 Change (n=283,274) |
0.9887
(6.52972)
|
0.5745
(6.45362)
|
| Sleep snoring Baseline (n=299,295) |
48.8815
(9.32313)
|
49.8895
(9.18885)
|
| Sleep snoring Day 28 Baseline (n=290,285) |
48.8234
(9.40239)
|
49.7733
(9.23030)
|
| Sleep snoring Day 28 Post (n=290,285) |
49.3476
(9.37744)
|
49.5067
(9.39012)
|
| Sleep snoring Day 28 change(n=290,285) |
0.5241
(6.70023)
|
-0.2667
(7.06825)
|
| Sleep snoring Day 84 Baseline (n=283,274) |
48.8414
(9.29113)
|
49.6385
(9.19681)
|
| Sleep snoring Day 84 post (n=283,274) |
49.4591
(9.29113)
|
49.6108
(9.51632)
|
| Sleep snoring Day 84 change (n=283,274) |
0.6177
(7.42456)
|
-0.0277
(8.266668)
|
| Sleep shortness of breath Baseline (n=302,295) |
44.5221
(13.28329)
|
45.4259
(11.51560)
|
| Sleep shortness of breath D 28 Bseline(n=293,285) |
44.6348
(13.15710)
|
45.3292
(11.48556)
|
| Sleep shortness of breath D 28 post (n=293,285) |
45.8814
(11.85664)
|
45.5774
(11.65379)
|
| Sleep shortness of breath D 28 change (n=293,285) |
1.2466
(12.21272)
|
0.2481
(11.44262)
|
| Sleep shortness of breath D 84 Bseline (n=287,274) |
44.8645
(12.99605)
|
45.3180
(11.37006)
|
| Sleep shortness of breath D 84 post (n=287,274) |
45.7676
(13.20151)
|
45.7049
(11.84910)
|
| Sleep shortness of breath D 84 change (n=287,274) |
0.9031
(12.11351)
|
0.3870
(10.97093)
|
| Sleep adequacy baseline (n=300,295) |
54.9999
(9.85865)
|
54.9725
(9.41704)
|
| Sleep adequacy baseline D 28 (n=291,285) |
55.0531
(9.80609)
|
55.0679
(9.30955)
|
| Sleep adequacy Post D 28 (n=291,285) |
55.2032
(10.04281)
|
54.8296
(10.21011)
|
| Sleep adequacy Change D 28 (n=291,285) |
0.1501
(9.83920)
|
-0.2383
(9.21250)
|
| Sleep adequacy baseline D 84 (n=284,274) |
55.2125
(9.81055)
|
55.1084
(9.20723)
|
| Sleep adequacy Post D 84 (n=284,274) |
55.2467
(10.00283)
|
54.5424
(9.96705)
|
| Sleep adequacy change D 84 (n=284,274) |
0.0342
(8.81793)
|
-0.5659
(8.57800)
|
| Sleep somnolence baseline (n=302,296) |
47.6646
(9.56376)
|
49.1709
(9.56807)
|
| Sleep somnolence baseline D28 (n=290,285) |
47.8711
(9.48940)
|
49.1092
(9.58808)
|
| Sleep somnolence post D28 (n=290,285) |
48.4429
(9.93046)
|
48.6761
(10.17850)
|
| Sleep somnolence change D28 (n=290,285) |
0.5718
(7.91162)
|
-0.4331
(8.67719)
|
| Sleep somnolence baseline D84 (n=284,274) |
47.7821
(9.53639)
|
48.9335
(9.55603)
|
| Sleep somnolence post D84 (n=284,274) |
48.2568
(10.36223)
|
49.0461
(9.54132)
|
| Sleep somnolence change D84 (n=284,274) |
0.4747
(8.11292)
|
0.1126
(7.83662)
|
| Sleep Problems Index 1 Baseline (n=300,295) |
50.4795
(9.72203)
|
50.8382
(9.16082)
|
| Sleep Problems Index 1 Baseline D28 (n=290,285) |
50.6034
(9.67464)
|
50.7911
(9.13425)
|
| Sleep Problems Index 1 Post D28 (n=290,285) |
51.4799
(9.86137)
|
50.7836
(10.02742)
|
| Sleep Problems Index 1 Change D28 (n=290,285) |
0.8764
(7.03960)
|
-0.0074
(7.73909)
|
| Sleep Problems Index 1 Baseline D84 (n=284,274) |
50.7327
(9.64776)
|
50.6951
(9.09626)
|
| Sleep Problems Index 1 Post D84 (n=284,274) |
51.3590
(10.16584)
|
50.9888
(9.54642)
|
| Sleep Problems Index 1 Change D84 (n=284,274) |
0.6263
(7.22742)
|
0.2938
(7.08082)
|
| Sleep Problems Index 2 baseline (n=299,295) |
50.4610
(9.14154)
|
51.0701
(8.62899)
|
| Sleep Problems Index 2 baseline D 28 (n=289,285) |
50.5720
(9.15508)
|
50.9923
(8.60656)
|
| Sleep Problems Index 2 Post D 28 (n=289,285) |
51.5578
(9.43365)
|
51.0116
(9.33837)
|
| Sleep Problems Index 2 Change D 28 (n=289,285) |
0.9858
(6.00711)
|
0.0193
(6.99119)
|
| Sleep Problems Index 2 Baseline D 84 (n=283,274) |
50.6880
(9.16092)
|
50.8848
(8.58893)
|
| Sleep Problems Index 2 Post D 84 (n=283,274) |
51.4615
(9.79518)
|
51.1511
(9.09673)
|
| Sleep Problems Index 2 Change D 84 (n=283,274) |
0.7735
(6.66709)
|
0.2663
(6.29393)
|
| Title | Patient Reported Outcome Measures: Medical Outcome Study (MOS) Sleep Scale: Sleep Quantity Subscale |
|---|---|
| Description | The sleep quantity subscale,which refers to question 2 of the PRO: On average, how many hours did you sleep each night during the past 4 weeks. More hours of sleep indicate better outcome. |
| Time Frame | Baseline, 4 and 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set.Higher scores show better outcomes.Excepting the sleep quantity subscale,scoring the MOS requires two steps:(a) assigning a point value to each response and (b) summing the point values for all the items in a given subscale or index. Each subscale and index score is then converted to a T score with a mean of 50 and an SD of 10. |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 302 | 296 |
| Sleep quantity Baseline (n=301,295) |
6.5565
(1.44169)
|
6.6203
(1.34895)
|
| Sleep quantity Baseline D28(n=292,285) |
6.5702
(1.44879)
|
6.6351
(1.35775)
|
| Sleep quantity Post D28(n=292,285) |
6.5717
(1.54708)
|
6.6246
(1.46356)
|
| Sleep quantity Change D28(n=292,285) |
0.0015
(1.07390)
|
-0.0105
(1.10691)
|
| Sleep quantity Baseline D84(n=285,274) |
6.5456
(1.42402)
|
6.6496
(1.34500)
|
| Sleep quantity Post D84(n=285,274) |
6.5561
(1.43780)
|
6.6569
(1.37648)
|
| Sleep quantity Change D84(n=285,274) |
0.0105
(1.12270)
|
0.0073
(1.18906)
|
| Title | Summary Statistics of COPD Exacerbations over12 Weeks as Defined by Chronic Pulmonary Disease Tool (EXACT) |
|---|---|
| Description | The EXACT is a 14-item electronic questionnaire designed to detect the frequency, severity, and duration of exacerbations in patients with COPD. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Mean (Standard Deviation) [COPD exacerbation per participant] |
0.2
(0.49)
|
0.3
(0.56)
|
| Title | Time to First COPD Exacerbation |
|---|---|
| Description | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. The reported measure will detail the percentage of participants that were event free of a specified event. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Mild COPD exacerbation |
99.3
31.4%
|
98.7
31.5%
|
| Moderate COPD exacerbation |
94.5
29.9%
|
88.5
28.3%
|
| Severe COPD exacerbation |
98.0
31%
|
98.3
31.4%
|
| Moderate or Severe COPD exacerbation |
92.9
29.4%
|
86.8
27.7%
|
| Any( mild, moderate,severe) |
92.2
29.2%
|
85.8
27.4%
|
| Title | Annual Rate of COPD Exacerbations |
|---|---|
| Description | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Model based estimates |
0.354
|
0.659
|
| Actual rate exacerbations per year |
0.39
|
0.73
|
| Title | Duration (in Days) of COPD Exacerbations |
|---|---|
| Description | Duration and number of the COPD exacerbation will be analyzed by the negative binomial regression model including treatment, country, smoking status, and COPD severity as factors and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Mean (Standard Deviation) [Days] |
1.4
(6.59)
|
2.0
(6.28)
|
| Title | Percentage of Patients With at Least One Exacerbation up to Week 12 |
|---|---|
| Description | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. The reported measure will detail the percentage of participants that had an exacerbation up to week 12. Less exacerbations reflect a better outcome. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Number [Percentage of participants] |
7.6
2.4%
|
14.1
4.5%
|
| Title | Time (in Days) to Permanent Study Discontinuation Due to COPD Exacerbation |
|---|---|
| Description | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Median (Inter-Quartile Range) [Days] |
NA
|
NA
|
| Title | The Percentage of Patients Who Permanently Discontinued Due to COPD Exacerbation |
|---|---|
| Description | Time-to-event variables will be analyzed by the Kaplan-Meier estimates and the stratified Cox proportional hazard model by smoking status and COPD severity. The model will include treatment and country as factors, and FEV1 prior to inhalation and FEV1 15 min post inhalation of salbutamol/albuterol as covariates. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| Number [Percentage participants] |
0.6
0.2%
|
1.6
0.5%
|
| Title | Total Amount (in Doses) of Systemic Corticosteroid Used to Treat COPD Exacerbation During the 12 Week Treatment Period |
|---|---|
| Description | Total amount (in doses) of systemic corticosteroid used to treat COPD exacerbation will be summarized descriptively by treatment group per each systemic corticosteroid. |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set consisting of all randomized patients |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 316 | 313 |
| IM Hydrocortisone (mg) (n=1,0) |
100
(0)
|
NA
(NA)
|
| IV dexamethasone (mg) (n=0,1) |
NA
(NA)
|
4.00
(0)
|
| IV Hydrocortisone (mg) (n=0,1) |
NA
(NA)
|
100
(0)
|
| IV Hydrocortisone sodium succinate (mg) (n=2,0) |
400.00
(282.843)
|
NA
(NA)
|
| IV methylprenisolone sodium succinate(mg)(n=1,0) |
250
(0)
|
NA
(NA)
|
| IV methylprenisolone sodium succinate(ug)(n=0,1) |
NA
(NA)
|
80
(0)
|
| IV prednisolone (mg) (n=0,1) |
NA
(NA)
|
250
(0)
|
| Oral Budesonide (mg) (n=0,1) |
NA
(NA)
|
20
(0)
|
| Oral methylprenisolone (mg) (n=7,13) |
16.57
(11.414)
|
20.31
(9.586)
|
| Oral prednisolone (mg) (n=8,28) |
24.38
(9.520)
|
23.93
(13.060)
|
| Oral prednisone (mg) (n=8,16) |
31.25
(11.260)
|
25.31
(11.176)
|
| Oral prednisone (ug) (n=0,1) |
NA
(NA)
|
10
(0)
|
| Inhalation budesonide (mL)(n=0,1) |
NA
(NA)
|
0.50
(0)
|
| Title | Plasma Cortisol Concentrations at Each Timepoint |
|---|---|
| Description | Plasma cortisol to be measured in a subset of approximately 60 patients via central laboratory. Blood sample for Plasma cortisol is collected at pre-dose and post dose up to 4 hour on Day 1, up to 12 hours post-dose on Day 28 and Day 84, and 23 hour 35 minute on Day 2, Day 29, and Day 85, and at pre-dose 25 minute on Day 28, and Day 84. |
| Time Frame | Day 1, Day 28, Day 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets. |
| Arm/Group Title | QMF149 | Salmeterol Xinafoate/Fluticasone Propionate |
|---|---|---|
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | Salmeterol xinafoate/fluticasone propionate 50/500 µg b.i.d, delivered via Accuhaler® |
| Measure Participants | 50 | 47 |
| Baseline (n=45,41) |
328.5
(149.56)
|
300.2
(107.36)
|
| Day 1 / 15 min (n=44,41) |
284.0
(151.96)
|
247.1
(91.99)
|
| Day 1 / 1 hr (n=44,41) |
249.1
(144.90)
|
223.0
(85.93)
|
| Day 1/ 4 hr (n=44,38) |
247.6
(85.90)
|
205.7
(68.65)
|
| Day 1 /23 hr 35 min (n=38,37) |
295.9
(153.80)
|
274.2
(115.33)
|
| Day 28/-25min (n=40,39) |
342.1
(160.16)
|
295.6
(98.78)
|
| Day 28 / 15 min (n=40,39) |
275.0
(140.83)
|
239.8
(90.14)
|
| Day 28 / 1 hr (n=40,39) |
255.9
(134.26)
|
211.9
(89.41)
|
| Day 28 / 4hr (n=40,38) |
241.9
(89.07)
|
203.6
(108.62)
|
| Day 28 / 11hr 35 min (n=40,37) |
124.8
(71.71)
|
124.1
(72.39)
|
| Day 28/ 23 hr 35 min (n=33,32) |
310.6
(99.81)
|
306.5
(119.33)
|
| Day 84 /-25 min (n=41,37) |
337.4
(155.24)
|
324.1
(104.01)
|
| Day 84/ 15 min (n=40,36) |
291.1
(144.26)
|
265.5
(103.39)
|
| Day 84/ 60 min (n=41,38) |
271.3
(158.88)
|
236.3
(104.06)
|
| Day 84/ 4 hr (n=41,38) |
268.4
(136.22)
|
224.2
(100.36)
|
| Day 84/ 11 hr 35 min (n=41,35) |
152.0
(99.66)
|
147.5
(108.21)
|
| Day 84 / 23 hr 35 min (n=37,36) |
339.9
(159.51)
|
315.9
(104.67)
|
| Title | Plasma Drug Concentrations (Pharmacokinetics) at Each Timepoint |
|---|---|
| Description | Plasma indacaterol and mometasone furoate is to be measured in a subset of approximately 60 patients via central laboratory. Blood samples are collected at pre-dose on Day 1, 29, and 84; and post dose up to 4 hour on Day 1, up to 12 hours on Day 28 and 84. For sparse pharmacokinetic testing, blood samples will be collected at 23h 35 min post-dose following morning dose administration on Day 28 and 84, in all patients participating in this study. |
| Time Frame | Day 1, 29, 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Moderate PK set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets. |
| Arm/Group Title | QMF149 (Analyte Mometasone Furoate) | QMF149 (Analyte Indacaterol Acetate) |
|---|---|---|
| Arm/Group Description | Assay Analyte: MOMETASONE FUROATE, component of QMF 149 mixture | Assay Analyte: QAB149 (Indacaterol acetate), component of QMF 149 mixture |
| Measure Participants | 50 | 50 |
| Day 1 time 0 (n=34,44) |
4.17
(13.8)
|
4.32
(12.3)
|
| Day 1 / 15 min (n=44,45) |
31.4
(17.9)
|
111
(52.1)
|
| Day 1 / 1 hr (n=43,45) |
44.6
(19.3)
|
89.7
(41.2)
|
| Day 1/ 4 hr (n=43,45) |
26.8
(15.6)
|
51.4
(33.5)
|
| Day 1 /23 hr 35 min (n=37, 38) |
13.1
(16.7)
|
44.8
(69.9)
|
| Day 28 0 time (n=41,42) |
14.5
(18.0)
|
82.0
(47.4)
|
| Day 28 / 15 min (n= 42,43) |
57.5
(31.6)
|
213
(98.0)
|
| Day 28 / 1 hr (n=41,42) |
68.4
(35.0)
|
194
(99.0)
|
| Day 28 / 4hr (n=42,42) |
43.7
(25.7)
|
132
(67.9)
|
| Day 28 / 11hr 35 min (n=41,42) |
19.2
(12.6)
|
86.6
(40.4)
|
| Day 28/ 23 hr 35 min (n=45,46) |
10.8
(7.32)
|
76.5
(38.1)
|
| Day 84 0 time (n=39,40) |
23.1
(30.5)
|
101
(50.8)
|
| Day 84/ 15 min (n=38,40) |
68.1
(41.4)
|
255
(129)
|
| Day 84/ 60 min (n=38,40) |
84.2
(40.6)
|
241
(119)
|
| Day 84/ 4 hr (n=40,40) |
49.9
(26.4)
|
161
(84.6)
|
| Day 84/ 11 hr 35 min (n=39,41) |
25.9
(21.2)
|
115
(67.5)
|
| Day 84 / 23 hr 35 min (n=44,45) |
14.6
(17.8)
|
98.7
(67.8)
|
| Title | Pharmacokinetic Parameter: Cmax |
|---|---|
| Description | Maximum observed plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84. |
| Time Frame | Day 28, 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Moderate PK set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets. |
| Arm/Group Title | QMF149 Analyte: Mometasone Furoate | QMF149 Analyte: Indacaterol Acetate |
|---|---|---|
| Arm/Group Description | Mometasone furoate as part of QMF149F | QAB149: indacaterol acetate as a component of QMF149F |
| Measure Participants | 50 | 50 |
| Day 28 (n=36,35) |
73.3
(24.9)
|
215
(71.5)
|
| Day 84 (n=32,35) |
80.2
(23.0)
|
263
(101)
|
| Title | Pharmacokinetic Parameter--Tmax |
|---|---|
| Description | Time to reach the maximum plasma concentration after drug administration is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84. |
| Time Frame | Day 28, 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Moderate PK set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets. |
| Arm/Group Title | QMF 149 Anaylyte: Mometasone Furorate | QMF149 Analyte: Indacaterol Acetate |
|---|---|---|
| Arm/Group Description | Mometasone furoate as a component of QMF149F | QAB149: indacaterol acetate as a component of QMF149F |
| Measure Participants | 50 | 50 |
| Day 28 (n= 36 ,35) |
0.250
(0.833)
|
0.970
(0.662)
|
| Day 84 (n= 32 ,35) |
0.250
(1.92)
|
1.00
(1.92)
|
| Title | Pharmacokinetic Parameter--AUC0-t |
|---|---|
| Description | Area under the plasma concentration time curve from time zero to time "t" post-dose is to be measured in a subset of approximately 60 patients via central laboratory, and will be determined for indacaterol and MF following morning dosing on Days 28 and 84. |
| Time Frame | Day 28, 84 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Moderate PK set: A total of 97 (15.4%) patients were included in the 24 h profiling FAS, safety plasma cortisol profiling subgroup, sparse and moderate PK sets. |
| Arm/Group Title | QMF149 Analyte Mometasone Furoate | QMF149 Analyte QAB149 |
|---|---|---|
| Arm/Group Description | QMF149 Mometasone furoate analyte from mixture | QMF149 analyte QAB149 ( indacaterol acetate) |
| Measure Participants | 50 | 50 |
| 28 Days (n=35,36) |
653
(296)
|
2400
(771)
|
| 84 Days (n=31,33) |
693
(297)
|
2760
(802)
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | QMF149 | SALM/FLUT | ||
| Arm/Group Description | QMF149 (Indacaterol acetate/Mometasone furoate) 150/160 µg o.d. delivered via Concept1 device | SALM/FLUT | ||
All Cause Mortality |
||||
| QMF149 | SALM/FLUT | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| QMF149 | SALM/FLUT | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/316 (3.2%) | 19/313 (6.1%) | ||
| Cardiac disorders | ||||
| ATRIAL FIBRILLATION | 1/316 (0.3%) | 2/313 (0.6%) | ||
| CORONARY ARTERY DISEASE | 1/316 (0.3%) | 0/313 (0%) | ||
| Gastrointestinal disorders | ||||
| ABDOMINAL PAIN | 0/316 (0%) | 1/313 (0.3%) | ||
| COLITIS | 0/316 (0%) | 1/313 (0.3%) | ||
| DIARRHOEA | 1/316 (0.3%) | 0/313 (0%) | ||
| GASTRIC ULCER HAEMORRHAGE | 0/316 (0%) | 1/313 (0.3%) | ||
| HAEMATOCHEZIA | 1/316 (0.3%) | 0/313 (0%) | ||
| SMALL INTESTINAL OBSTRUCTION | 1/316 (0.3%) | 0/313 (0%) | ||
| General disorders | ||||
| MALAISE | 1/316 (0.3%) | 0/313 (0%) | ||
| Hepatobiliary disorders | ||||
| CHOLECYSTITIS | 0/316 (0%) | 1/313 (0.3%) | ||
| Infections and infestations | ||||
| INCISION SITE INFECTION | 1/316 (0.3%) | 0/313 (0%) | ||
| LOBAR PNEUMONIA | 0/316 (0%) | 1/313 (0.3%) | ||
| PNEUMONIA | 2/316 (0.6%) | 0/313 (0%) | ||
| SPUTUM PURULENT | 1/316 (0.3%) | 0/313 (0%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 1/316 (0.3%) | 0/313 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| UPPER LIMB FRACTURE | 0/316 (0%) | 1/313 (0.3%) | ||
| Investigations | ||||
| ELECTROCARDIOGRAM T WAVE INVERSION | 0/316 (0%) | 2/313 (0.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| OSTEOARTHRITIS | 1/316 (0.3%) | 0/313 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| PLEURAL MESOTHELIOMA MALIGNANT | 0/316 (0%) | 1/313 (0.3%) | ||
| Nervous system disorders | ||||
| INTRACRANIAL ANEURYSM | 0/316 (0%) | 1/313 (0.3%) | ||
| TEMPORAL LOBE EPILEPSY | 0/316 (0%) | 1/313 (0.3%) | ||
| TENSION HEADACHE | 0/316 (0%) | 1/313 (0.3%) | ||
| Renal and urinary disorders | ||||
| HAEMATURIA | 0/316 (0%) | 1/313 (0.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| ATELECTASIS | 0/316 (0%) | 1/313 (0.3%) | ||
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 6/316 (1.9%) | 5/313 (1.6%) | ||
| COUGH | 1/316 (0.3%) | 0/313 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| QMF149 | SALM/FLUT | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 79/316 (25%) | 83/313 (26.5%) | ||
| Gastrointestinal disorders | ||||
| DRY MOUTH | 4/316 (1.3%) | 1/313 (0.3%) | ||
| NAUSEA | 4/316 (1.3%) | 0/313 (0%) | ||
| General disorders | ||||
| FATIGUE | 3/316 (0.9%) | 4/313 (1.3%) | ||
| PYREXIA | 6/316 (1.9%) | 3/313 (1%) | ||
| Infections and infestations | ||||
| NASOPHARYNGITIS | 12/316 (3.8%) | 8/313 (2.6%) | ||
| RHINITIS | 8/316 (2.5%) | 2/313 (0.6%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 4/316 (1.3%) | 4/313 (1.3%) | ||
| Investigations | ||||
| C-REACTIVE PROTEIN INCREASED | 6/316 (1.9%) | 2/313 (0.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| MUSCLE SPASMS | 5/316 (1.6%) | 2/313 (0.6%) | ||
| Nervous system disorders | ||||
| DIZZINESS | 4/316 (1.3%) | 0/313 (0%) | ||
| HEADACHE | 10/316 (3.2%) | 5/313 (1.6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 19/316 (6%) | 43/313 (13.7%) | ||
| COUGH | 9/316 (2.8%) | 5/313 (1.6%) | ||
| DYSPNOEA | 7/316 (2.2%) | 10/313 (3.2%) | ||
| OROPHARYNGEAL PAIN | 6/316 (1.9%) | 3/313 (1%) | ||
| RHINORRHOEA | 2/316 (0.6%) | 6/313 (1.9%) | ||
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 (ie, data from all sites) in the clinical trial
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01636076
Other Study ID Numbers:
- CQMF149F2202
- 2012-001172-12
First Posted:
Jul 10, 2012
Last Update Posted:
Nov 17, 2014
Last Verified:
Nov 1, 2014