Effect of Tiotropium Plus Salmeterol vs. Fluticasone/Salmeterol on Static Lung Volumes and Exercise Endurance in COPD

Pulmonary Disease, Chronic Obstructive Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00530842
• Other study ID #: 205.334
• Status: Completed
• Phase: Phase 4
• First received: September 17, 2007
• Last updated: November 27, 2013
• Start date: September 2007

Study information

• Verified date: September 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 ViennaCanada: Health Canada, Therapeutic Products DirectorateFrance: Agence Française de Sécurité Sanitaire des Produits de Santé 143-147 boulevard Anatole France 93285Germany: BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte)Italy: Comitato Etico per la Sperimentazione Clinica dei Medicinali dell'A.O. Univ. Pisana di PisaRussia: Ministry of Healthcare and Social Development of Russian Federation, MoscowSweden: Medical Products Agency Regional Ethics Committee of UppsalaUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Tiotropium plus Salmeterol

• Fluticasone/Salmeterol

Locations

Country	Name	City	State
Austria	205.334.4309 Boehringer Ingelheim Investigational Site	Gänserndorf
Austria	205.334.4308 Boehringer Ingelheim Investigational Site	Hallein
Austria	205.334.4306 Boehringer Ingelheim Investigational Site	Leoben
Austria	205.334.4301 Boehringer Ingelheim Investigational Site	Linz
Austria	205.334.4302 Boehringer Ingelheim Investigational Site	Neumarkt am Wallersee
Austria	205.334.4305 Boehringer Ingelheim Investigational Site	Salzburg
Canada	205.334.1003 Boehringer Ingelheim Investigational Site	Halifax	Nova Scotia
Canada	205.334.1005 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	205.334.1008 Boehringer Ingelheim Investigational Site	Kingston	Ontario
Canada	205.334.1001 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	205.334.1004 Boehringer Ingelheim Investigational Site	Ottawa	Ontario
Canada	205.334.1006 Boehringer Ingelheim Investigational Site	Quebec
Canada	205.334.1007 Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan
Canada	205.334.1010 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	205.334.1009 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
France	205.334.3303A Boehringer Ingelheim Investigational Site	Beuvry
France	205.334.3303B Boehringer Ingelheim Investigational Site	Beuvry
France	205.334.3305A Boehringer Ingelheim Investigational Site	Créteil
France	205.334.3301A Boehringer Ingelheim Investigational Site	Grenoble
France	205.334.3304A Boehringer Ingelheim Investigational Site	St Priest en Jarez
France	205.334.3306A Boehringer Ingelheim Investigational Site	Strasbourg
France	205.334.3306B Boehringer Ingelheim Investigational Site	Strasbourg
France	205.334.3302A Boehringer Ingelheim Investigational Site	Toulouse
France	205.334.3302B Boehringer Ingelheim Investigational Site	Toulouse
Germany	205.334.4908 Boehringer Ingelheim Investigational Site	Berlin
Germany	205.334.4909 Boehringer Ingelheim Investigational Site	Berlin
Germany	205.334.4904 Boehringer Ingelheim Investigational Site	Donaustauf
Germany	205.334.4901 Boehringer Ingelheim Investigational Site	Großhansdorf
Germany	205.334.4907 Boehringer Ingelheim Investigational Site	Kiel
Germany	205.334.4902 Boehringer Ingelheim Investigational Site	Köln
Italy	205.334.39007 Boehringer Ingelheim Investigational Site	Catania
Italy	205.334.39002 Boehringer Ingelheim Investigational Site	Gaiato Pavullo (mo)
Italy	205.334.39004 Boehringer Ingelheim Investigational Site	Milano
Italy	205.334.39001 Boehringer Ingelheim Investigational Site	Pisa
Italy	205.334.39005 Boehringer Ingelheim Investigational Site	Roma
Italy	205.334.39006 Boehringer Ingelheim Investigational Site	Roma
Russian Federation	205.334.7001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.334.7002 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.334.7003 Boehringer Ingelheim Investigational Site	St. Petersburg
Sweden	205.334.46003 Boehringer Ingelheim Investigational Site	Jönköping
Sweden	205.334.46002 Boehringer Ingelheim Investigational Site	Lund
Sweden	205.334.46001 Boehringer Ingelheim Investigational Site	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Canada,  France,  Germany,  Italy,  Russian Federation,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-dose TGV(FRC) (After 8 Weeks)	Post-dose TGV(FRC) (Thoracic Gas Volume; co-primary endpoint) after 8 weeks	8 weeks	No
Primary	Endurance Time (After 8 Weeks)	Endurance time to the point of symptom limitation after 8 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)	8 weeks	No
Secondary	Post-dose TGV(FRC) (After 4 Weeks)	Post-dose TGV(FRC) (Thoracic Gas Volume) after 4 weeks	4 weeks	No
Secondary	Endurance Time (After 4 Weeks)	Endurance time to the point of symptom limitation after 4 weeks during a constant work rate exercise test at 75% Wcap (co-primary endpoint)	4 weeks	No
Secondary	Static Lung Volumes	Trough TGV(FRC) (Thoracic Gas Volume) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes	Trough TGV(FRC) (Thoracic Gas Volume) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes	Trough RV (Residual Volume) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes	Trough RV (Residual Volume) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes	Post-dose RV (Residual Volume) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes	Post-dose RV (Residual Volume) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes	Trough IC (Inspiratory Capacity) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes	Trough IC (Inspiratory Capacity) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes	Post-dose IC (Inspiratory Capacity) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes	Post-dose IC (Inspiratory Capacity) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes	Trough IRV (Inspiratory Reserve Volume) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes	Trough IRV (Inspiratory Reserve Volume) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes	Post-dose IRV (Inspiratory Reserve Volume) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes	Post-dose IRV (Inspiratory Reserve Volume) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes	Trough TLC (Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes	Trough TLC (Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes	Post-dose TLC (Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes	Post-dose TLC (Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes (Percent)	Trough RV/TLC (Residual Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes (Percent)	Trough RV/TLC (Residual Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes (Percent)	Post-dose RV/TLC (Residual Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes (Percent)	Post-dose RV/TLC (Residual Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes (Percent)	Trough TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes (Percent)	Trough TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Static Lung Volumes (Percent)	Post-dose TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 8 weeks (measured by bodyphlethysmography)	8 weeks	No
Secondary	Static Lung Volumes (Percent)	Post-dose TGV/TLC (Thoracic Gas Volume over Total Lung Capacity) after 4 weeks (measured by bodyphlethysmography)	4 weeks	No
Secondary	Slow Vital Capacity (SVC)	Trough SVC (Slow Vital Capacity) after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	Slow Vital Capacity (SVC)	Trough SVC (Slow Vital Capacity) after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	Slow Vital Capacity (SVC)	Post-dose SVC (Slow Vital Capacity) after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	Slow Vital Capacity (SVC)	Post-dose SVC (Slow Vital Capacity) after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)	Trough FEV1 (Forced Expiratory Volume in 1 second) after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)	Trough FEV1 (Forced Expiratory Volume in 1 second) after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)	Post-dose FEV1 (Forced Expiratory Volume in 1 second) after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)	Post-dose FEV1 (Forced Expiratory Volume in 1 second) after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)	Trough percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)	Trough percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)	Post-dose percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1)	Post-dose percent predicted FEV1 (Forced Expiratory Volume in 1 second) according to ECCS after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	Forced Vital Capacity (FVC)	Trough FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	Forced Vital Capacity (FVC)	Trough FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	Forced Vital Capacity (FVC)	Post-dose FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	Forced Vital Capacity (FVC)	Post-dose FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	FEV1 Over FVC (Percent)	Trough FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	FEV1 Over FVC (Percent)	Trough FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	FEV1 Over FVC (Percent)	Post-dose FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 8 weeks (measured by spirometry)	8 weeks	No
Secondary	FEV1 Over FVC (Percent)	Post-dose FEV1 (Forced Expiratory Volume in 1 second) over FVC (Forced Vital Capacity) after 4 weeks (measured by spirometry)	4 weeks	No
Secondary	Symptom Intensity During Exercise	Isotime Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10), 0 = no dyspnea, 10 = worst imaginable dyspnea	8 weeks	No
Secondary	Symptom Intensity During Exercise	Isotime Borg dyspnea scale after 4 weeks, Unit on a Scale (min. 0, max. 10), 0 = no dyspnea, 10 = worst imaginable dyspnea	4 weeks	No
Secondary	Symptom Intensity During Exercise	Isotime Borg leg discomfort scale after 8 weeks, Unit on a Scale (min. 0, max. 10), 0 = no leg dyscomfort, 10 = worst imaginable leg dyscomfort	8 weeks	No
Secondary	Symptom Intensity During Exercise	Isotime Borg leg discomfort scale after 4 weeks, Unit on a Scale (min. 0, max. 10), 0 = no leg dyscomfort, 10 = worst imaginable leg dyscomfort	4 weeks	No
Secondary	Dyspnea and Leg Discomfort	Peak Borg dyspnea scale after 8 weeks, Unit on a Scale (min. 0, max 10)	8 weeks	No
Secondary	Dyspnea and Leg Discomfort	Peak Borg leg discomfort scale after 8 weeks, Unit on a Scale (min. 0, max 10)	8 weeks	No
Secondary	Locus of Symptom Limitation at Peak Exercise During Exercise	Reason for stopping exercise at baseline (leg discomfort, breathing discomfort, both or none)	baseline	No
Secondary	Locus of Symptom Limitation at Peak Exercise During Exercise	Reason for stopping exercise after 4 weeks (leg discomfort, breathing discomfort, both or none)	4 weeks	No
Secondary	Locus of Symptom Limitation at Peak Exercise During Exercise	Reason for stopping exercise after 8 weeks (leg discomfort, breathing discomfort, both or none)	8 weeks	No

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