Efficacy and Safety Comparison of Tiotropium Daily + Salmeterol Daily or Twice Daily Versus Tiotropium Daily in Patients With COPD

This study has been completed.
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
First received: April 17, 2008
Last updated: April 30, 2014
Last verified: April 2014
The primary objective of this trial is to establish superiority of the once-daily Tiotropium plus Salmeterol Inhalation Powder in daytime lung function response and non-inferiority in night-time lung function response over the comparator treatments inhaled in their established dose regimens when administered for 6-week periods to patients with chronic obstructive pulmonary disease (COPD). The main secondary objective is to evaluate the safety of the Tiotropium plus Salmeterol Inhalation Powder versus the comparator treatments.

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium plus Salmeterol
Drug: Tiotropium
Drug: Salmeterol
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind Clinical Efficacy and Safety Comparison of Tiotropium/Salmeterol 7.5/25 Inhalation Powder in the Morning Via Tiotropium/Salmeterol HandiHaler, Tiotropium 18 Mcg Inhalation Powder in the Morning Via Spiriva HandiHaler, Salmeterol 50 Mcg MDPI in the Morning and Evening and the Free Combination Tiotropium 18 Mcg Inhalation Powder in the Morning Via Spiriva HandiHaler Plus Salmeterol 50 Mcg MDPI in the Morning and Evening Following Chronic Administration (6-week Treatment Periods) in Patients With COPD

Resource links provided by NLM:

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Area under the curve for FEV1 in the daytime (FEV1 AUC0-12) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • peak FEV1 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Area under the curve for FEV1 in the night-time (FEV1 AUC12-24) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • trough FEV1 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • FEV1 AUC0-24 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • FVC AUC0-12, peak FVC, FVC AUC12-24, trough FVC, FVC AUC0-24 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • peak expiratory flow (PEF) AUC0-12, peak PEF, PEF AUC12-24, trough PEF, PEF AUC0-24 [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Individual FEV1, FVC, and PEF over a 24-h observation period [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Morning and evening PEF and FEV1 recorded by the patients at home [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Number of days with rescue medication use and number of puffs of rescue medication (daytime, night-time, and 24 h) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Number of awakenings due to shortness of breath (SOB), number of days with night-time awakenings, number of days with night-time awakenings due to SOB, and average SOB score at night [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Pulse rate [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Blood pressure [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 147
Study Start Date: April 2008
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. All patients must sign an informed consent consistent with ICH-GCP guidelines and local legislations prior to any study-related procedures, which includes medication washout and restrictions.
  2. All patients must have a diagnosis of COPD and must meet the following criteria:

    relatively stable* airway obstruction with a post-bronchodilator FEV1 < 80% of predicted normal and post-bronchodilator FEV1 < 70% of post-bronchodilator FVC at Visit 1 (according to GOLD criteria).

    * The randomisation of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the Screening Visit (Visit 1) or during the baseline period should be postponed. Patients may be randomised 6 weeks following recovery from the infection or exacerbation. Predicted normal values will be calculated according to ECSC.

  3. Male or female patients 40 years of age or older.
  4. Patients must be current or ex-smokers with a smoking history of 10 pack-years.
  5. Patients must be able to perform technically acceptable pulmonary function tests
  6. Patients must be able to inhale medication in a competent manner.
  7. Patients must be able to perform all necessary recordings in the diary.

Exclusion Criteria:

  1. Significant diseases other than COPD
  2. Patients with clinically significant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a significant disease as defined in exclusion criterion No. 1.
  3. Patients with a recent history of myocardial infarction.
  4. Patients with any unstable or life-threatening cardiac arrhythmia requiring intervention or change in drug therapy during the past year.
  5. Hospitalisation for cardiac failure during the past year.
  6. Malignancy within the last five years excluded basal cell carcinoma.
  7. Patients with a history of asthma or who have a total blood eosinophil count 600/mm3.
  8. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis.
  9. Known active tuberculosis.
  10. Patients with a history of alcohol or drug abuse.
  11. Thoracotomy with pulmonary resection.
  12. Rehabilitation program within the last six weeks
  13. Patients who regularly use daytime oxygen therapy
  14. Patients who have taken an investigational drug within 30 days
  15. Use of not allowed medications
  16. Known hypersensitivity to used drugs or other components of the study medication.
  17. Pregnant or nursing women
  18. Women of childbearing potential not using a highly effective method of birth control. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomised partner. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.
  19. Patients who are currently participating in another study.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00662792

1184.13.1302 Boehringer Ingelheim Investigational Site
Berlin, Germany
1184.13.1309 Boehringer Ingelheim Investigational Site
Berlin, Germany
1184.13.1308 Boehringer Ingelheim Investigational Site
Cottbus, Germany
1184.13.1311 Boehringer Ingelheim Investigational Site
Großhansdorf, Germany
1184.13.1312 Boehringer Ingelheim Investigational Site
Hamburg, Germany
1184.13.1305 Boehringer Ingelheim Investigational Site
Mainz, Germany
1184.13.1301 Boehringer Ingelheim Investigational Site
Mannheim, Germany
1184.13.1306 Boehringer Ingelheim Investigational Site
Rodgau-Dudenhofen, Germany
1184.13.1310 Boehringer Ingelheim Investigational Site
Rüdersdorf, Germany
1184.13.1307 Boehringer Ingelheim Investigational Site
Schwerin, Germany
1184.13.1304 Boehringer Ingelheim Investigational Site
Wiesbaden, Germany
1184.13.1303 Boehringer Ingelheim Investigational Site
Wiesloch, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00662792     History of Changes
Other Study ID Numbers: 1184.13  n.a. 
Study First Received: April 17, 2008
Last Updated: April 30, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Lung Diseases
Lung Diseases, Obstructive
Pathologic Processes
Respiratory Tract Diseases
Salmeterol Xinafoate
Tiotropium Bromide
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Respiratory System Agents

ClinicalTrials.gov processed this record on May 26, 2016