Clinical trial NCT00530842: Effect of Tiotropium Plus Salmeterol vs. Fluticasone/Salmeterol on Static Lung Volumes and Exercise Endurance in COPD
Official title: Effect of Inhalation of a Free Combination of Tiotropium Once Daily 18 Mcg and Salmeterol Twice Daily 50 Mcg Versus a Fixed Combination of Fluticasone and Salmeterol Twice Daily (500/50 Mcg) on Static Lung Volumes and Exercise Tolerance in COPD Patients (a Randomised, Double-blind, Double Dummy, 16 (2 x 8) Weeks, Crossover Study).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-09-18
Enrollment: 344
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to demonstrate that treatment with a free combination of tiotropium and salmeterol provides superior improvement in static lung volumes and exercise tolerance compared to a fixed combination of fluticasone and salmeterol in patients with COPD.

The secondary objective includes assessment of safety.


Eligibility criteria: Inclusion Criteria:

1. The patient has signed an Informed Consent Form in accordance with GCP and local legislative requirements prior to participation in the trial, i.e., prior to pre-trial washout of any restricted medications.
2. The patient has a clinical diagnosis of chronic obstructive pulmonary disease (COPD).
3. The patient has relatively stable, moderate to severe airway obstruction.
4. The patient has a pre-bronchodilator forced expiratory volume in the first second (FEV1) less than or equal to 65% of predicted normal determined at Visit 1 using the following predicted equations (R94-1408):

   1. Males Forced expiratory volume in the first second (FEV1) predicted \[Litres (L)\] = 4.30 x Height \[metres\] minus 0.029 x Age \[years\] minus 2.49
   2. Females Forced expiratory volume in the first second (FEV1) predicted \[Litres (L)\] = 3.95 x Height \[metres\] minus 0.025 x Age \[years\] minus 2.60 and a Thoracic Gas Volume (Functional residual volume) ((TGV)(FRC)) bigger than 120% predicted normal at visit 1 (or historical data not older than 6 month)
   3. Males Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. \[Litres (L)\] = 2.34 x Height \[metres\] + 0.009 x Age \[years\] minus 1.09
   4. Females Thoracic Gas Volume (Functional residual volume) ((TGV(FRC)) pred. \[Litres (L)\] = 2.24 x Height \[metres\] + 0.001 x Age \[years\] minus 1.00
5. The patient is at least 40 years and less than or equal to 75 years old.
6. The patient has a cigarette smoking history of at least 10 pack-years. A pack-year is defined as the equivalent of smoking one pack of cigarettes per day for a year.
7. The patient is able to perform all specified procedures and able to maintain all necessary records during the study period as required in the protocol.
8. The patient is able to inhale the trial medication from the HandiHaler device.
9. The patient is able to inhale the trial medication from the Diskus/Accuhaler device.

Exclusion Criteria:

1. a significant disease other than chronic obstructive pulmonary disease (COPD). (review contraindications for exercise testing),
2. a recent history of myocardial infarction within one year.
3. a recent history of heart failure, pulmonary oedema, or patients with cardiac arrhythmia or any contraindication to exercise described in the CTProtocol within the last 3.
4. daytime supplemental oxygen.
5. a diagnosis of known active tuberculosis.
6. a history of cancer within the last 5 years.
7. a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
8. thoracotomy with pulmonary resection.
9. an upper respiratory tract infection or an exacerbation of chronic obstructive pulmonary disease (COPD)
10. a known hypersensitivity to anticholinergic drug, ß-adrenergic or corticosteroids, lactose or any other component of the inhalation capsule delivery system.
11. a known symptomatic prostatic hypertrophy or bladder neck obstruction.
12. a known moderate or severe renal insufficiency.
13. a known narrow-angle glaucoma.
14. a known untreated hypokalemia.
15. a known untreated thyrotoxicosis.
16. a history of asthma, allergic rhinitis or atopy, or a total blood eosinophil count larger than 600/mm3.
17. treatment with cromolyn sodium or nedocromil sodium
18. treatment with antihistamines or antileukotrienes.
19. treatment with tiotropium for 1 month before Visit 1.
20. treatment with oral corticosteroid medication.
21. Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception
22. a history of or active alcohol or drug abuse.
23. an investigational drug within 1 month or 10 half lives
24. a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnoea.
25. participation in a rehabilitation program for chronic obstructive pulmonary disease (COPD).
26. treatment with monoamine oxidase inhibitors inhibitors or tricyclic antidepressants.
27. participation in another study.
28. more than eight puffs of salbutamol/day during the run-in period

Primary outcomes:
measure: Post-dose TGV(FRC) (After 8 Weeks)
timeFrame: 8 weeks
measure: Endurance Time (After 8 Weeks)
timeFrame: 8 weeks
Secondary outcomes:
measure: Post-dose TGV(FRC) (After 4 Weeks)
timeFrame: 4 weeks
measure: Endurance Time (After 4 Weeks)
timeFrame: 4 weeks
measure: Static Lung Volumes
timeFrame: 8 weeks
measure: Static Lung Volumes
timeFrame: 4 weeks
measure: Static Lung Volumes
timeFrame: 8 weeks
measure: Static Lung Volumes
timeFrame: 4 weeks
measure: Static Lung Volumes
timeFrame: 8 weeks
measure: Static Lung Volumes
timeFrame: 4 weeks
measure: Static Lung Volumes
timeFrame: 8 weeks
measure: Static Lung Volumes
timeFrame: 4 weeks
measure: Static Lung Volumes
timeFrame: 8 weeks
measure: Static Lung Volumes
timeFrame: 4 weeks
measure: Static Lung Volumes
timeFrame: 8 weeks
measure: Static Lung Volumes
timeFrame: 4 weeks
measure: Static Lung Volumes
timeFrame: 8 weeks
measure: Static Lung Volumes
timeFrame: 4 weeks
measure: Static Lung Volumes
timeFrame: 8 weeks
measure: Static Lung Volumes
timeFrame: 4 weeks
measure: Static Lung Volumes
timeFrame: 8 weeks
measure: Static Lung Volumes
timeFrame: 4 weeks
measure: Static Lung Volumes (Percent)
timeFrame: 8 weeks
measure: Static Lung Volumes (Percent)
timeFrame: 4 weeks
measure: Static Lung Volumes (Percent)
timeFrame: 8 weeks
measure: Static Lung Volumes (Percent)
timeFrame: 4 weeks
measure: Static Lung Volumes (Percent)
timeFrame: 8 weeks
measure: Static Lung Volumes (Percent)
timeFrame: 4 weeks
measure: Static Lung Volumes (Percent)
timeFrame: 8 weeks
measure: Static Lung Volumes (Percent)
timeFrame: 4 weeks
measure: Slow Vital Capacity (SVC)
timeFrame: 8 weeks
measure: Slow Vital Capacity (SVC)
timeFrame: 4 weeks
measure: Slow Vital Capacity (SVC)
timeFrame: 8 weeks
measure: Slow Vital Capacity (SVC)
timeFrame: 4 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 8 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 4 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 8 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 4 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 8 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 4 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 8 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 4 weeks
measure: Forced Vital Capacity (FVC)
timeFrame: 8 weeks
measure: Forced Vital Capacity (FVC)
timeFrame: 4 weeks
measure: Forced Vital Capacity (FVC)
timeFrame: 8 weeks
measure: Forced Vital Capacity (FVC)
timeFrame: 4 weeks
measure: FEV1 Over FVC (Percent)
timeFrame: 8 weeks
measure: FEV1 Over FVC (Percent)
timeFrame: 4 weeks
measure: FEV1 Over FVC (Percent)
timeFrame: 8 weeks
measure: FEV1 Over FVC (Percent)
timeFrame: 4 weeks
measure: Symptom Intensity During Exercise
timeFrame: 8 weeks
measure: Symptom Intensity During Exercise
timeFrame: 4 weeks
measure: Symptom Intensity During Exercise
timeFrame: 8 weeks
measure: Symptom Intensity During Exercise
timeFrame: 4 weeks
measure: Dyspnea and Leg Discomfort
timeFrame: 8 weeks
measure: Dyspnea and Leg Discomfort
timeFrame: 8 weeks
measure: Locus of Symptom Limitation at Peak Exercise During Exercise
timeFrame: baseline
measure: Locus of Symptom Limitation at Peak Exercise During Exercise
timeFrame: 4 weeks
measure: Locus of Symptom Limitation at Peak Exercise During Exercise
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Gänserndorf
country: Austria
facility: 205.334.4309 Boehringer Ingelheim Investigational Site
city: Hallein
country: Austria
facility: 205.334.4308 Boehringer Ingelheim Investigational Site
city: Leoben
country: Austria
facility: 205.334.4306 Boehringer Ingelheim Investigational Site
city: Linz
country: Austria
facility: 205.334.4301 Boehringer Ingelheim Investigational Site
city: Neumarkt am Wallersee
country: Austria
facility: 205.334.4302 Boehringer Ingelheim Investigational Site
city: Salzburg
country: Austria
facility: 205.334.4305 Boehringer Ingelheim Investigational Site
city: Vancouver
country: Canada
facility: 205.334.1009 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Halifax
country: Canada
facility: 205.334.1003 Boehringer Ingelheim Investigational Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: 205.334.1005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Kingston
country: Canada
facility: 205.334.1008 Boehringer Ingelheim Investigational Site
state: Ontario
city: Ottawa
country: Canada
facility: 205.334.1004 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 205.334.1010 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 205.334.1001 Boehringer Ingelheim Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: 205.334.1007 Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Quebec
country: Canada
facility: 205.334.1006 Boehringer Ingelheim Investigational Site
city: Beuvry
country: France
facility: 205.334.3303A Boehringer Ingelheim Investigational Site
city: Beuvry
country: France
facility: 205.334.3303B Boehringer Ingelheim Investigational Site
city: Créteil
country: France
facility: 205.334.3305A Boehringer Ingelheim Investigational Site
city: Grenoble
country: France
facility: 205.334.3301A Boehringer Ingelheim Investigational Site
city: St Priest en Jarez
country: France
facility: 205.334.3304A Boehringer Ingelheim Investigational Site
city: Strasbourg
country: France
facility: 205.334.3306A Boehringer Ingelheim Investigational Site
city: Strasbourg
country: France
facility: 205.334.3306B Boehringer Ingelheim Investigational Site
city: Toulouse
country: France
facility: 205.334.3302A Boehringer Ingelheim Investigational Site
city: Toulouse
country: France
facility: 205.334.3302B Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 205.334.4908 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 205.334.4909 Boehringer Ingelheim Investigational Site
city: Donaustauf
country: Germany
facility: 205.334.4904 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 205.334.4901 Boehringer Ingelheim Investigational Site
city: Kiel
country: Germany
facility: 205.334.4907 Boehringer Ingelheim Investigational Site
city: Köln
country: Germany
facility: 205.334.4902 Boehringer Ingelheim Investigational Site
city: Catania
country: Italy
facility: 205.334.39007 Boehringer Ingelheim Investigational Site
city: Gaiato Pavullo (mo)
country: Italy
facility: 205.334.39002 Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: 205.334.39004 Boehringer Ingelheim Investigational Site
city: Pisa
country: Italy
facility: 205.334.39001 Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: 205.334.39005 Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: 205.334.39006 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.334.7001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.334.7002 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 205.334.7003 Boehringer Ingelheim Investigational Site
city: Jönköping
country: Sweden
facility: 205.334.46003 Boehringer Ingelheim Investigational Site
city: Lund
country: Sweden
facility: 205.334.46002 Boehringer Ingelheim Investigational Site
city: Uppsala
country: Sweden
facility: 205.334.46001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Magnussen H, Paggiaro P, Schmidt H, Kesten S, Metzdorf N, Maltais F. Effect of combination treatment on lung volumes and exercise endurance time in COPD. Respir Med. 2012 Oct;106(10):1413-20. doi: 10.1016/j.rmed.2012.05.011. Epub 2012 Jun 28.