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Tiotropium / Respimat One-Year Study

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00168831
First received: September 12, 2005
Last updated: May 15, 2014
Last verified: September 2013
  Purpose

To evaluate the long term effects of treatment with two doses of Tiotropium delivered by the Respimat inhaler in patients with COPD.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium Inhalation Solution
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Efficacy and Safety Comparison of One-Year Treatment of Two Doses (5mg and 10mg) of Tiotropium Inhalation Solution Delivered by the Respimat Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Change From Baseline in Trough FEV1 After 48 Weeks [ Time Frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication ] [ Designated as safety issue: No ]
    Change From Baseline in Trough Forced Expiratory Volume in 1 second (FEV1) after 48 weeks

  • Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Rating scale of 3 domains - symptoms, activities and impact (weighted). Worst score = 100, best score = 0

  • TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies) [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

    Rating scale of 3 components - change in functional impairment, change in magnitude of tasks, change in magnitude of efforts. Worst score = -9, best score = +9

    For this endpoint data of twin studies NCT00168844 and NCT00168831 was combined.


  • COPD Exacerbation Rate, Safety Set (SS) (Combined Studies) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    Number of Chronic Obstructive Pulmonary Disease (COPD) exacerbations per patient year

    For this endpoint data of the twin studies NCT00168844 and NCT00168831 was combined.



Secondary Outcome Measures:
  • Change From Baseline in Heart Rate [ Time Frame: Baseline to Week 40 pre-dose ] [ Designated as safety issue: No ]
    Week 40 pre-dose - baseline

  • Change From Baseline in PR Interval [ Time Frame: Baseline to Week 40 pre-dose ] [ Designated as safety issue: No ]
  • Change From Baseline in QRS Interval [ Time Frame: Baseline to Week 40 pre-dose ] [ Designated as safety issue: No ]
    Week 40 pre-dose - baseline

  • Change From Baseline in QT Interval [ Time Frame: Baseline to Week 40 pre-dose ] [ Designated as safety issue: No ]
    Week 40 pre-dose - baseline

  • Change From Baseline in QT Interval (Bazett) [ Time Frame: Baseline to Week 40 pre-dose ] [ Designated as safety issue: No ]
    Week 40 pre-dose - baseline

  • Change From Baseline in QT Interval (Fridericia) [ Time Frame: Baseline to Week 40 pre-dose ] [ Designated as safety issue: No ]
    Week 40 pre-dose - baseline

  • Change From Baseline in Heart Rate [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
    Week 40 - baseline

  • Change From Baseline in Supraventricular Premature Beat (SVPB) Total [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
    Week 40 - baseline

  • Change From Baseline in SVPB Run Events [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
    Week 40 - baseline

  • Change From Baseline in SVPB Pairs [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
    Week 40 - baseline

  • Change From Baseline in Ventricular Premature Beat (VPB) Total [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
    Week 40 - baseline

  • Change From Baseline in Ventricular Premature Beat (VPB) Run Events [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
    Week 40 - baseline

  • Change From Baseline in VPB Pairs [ Time Frame: Baseline to Week 40 ] [ Designated as safety issue: No ]
    Week 40 - baseline

  • Change From Baseline in Haematocrit, Packed Cell Volume (PCV) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
  • Change From Baseline in Haemoglobin [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Red Blood Cell Count [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in White Blood Cell Count [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Platelets [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Neutrophils [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Eosinophils [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Basophils [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Lymphocytes [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Monocytes [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Neutrophils (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Eosinophils (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Basophils (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Lymphocytes (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Monocytes (Absolute) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Calcium [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Phosphate [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Aspartate Transaminase/Glutamic-oxaloacetic Transaminase (AST/GOT), Serum Glutamic-oxaloacetic Transaminase (SGOT) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Alanine Transaminase/Glutamic Pyruvate Transaminase (ALT/GPT), Serum Glutamate Pyruvate Transaminase (SGPT) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Alkaline Phosphatase [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Lactic Dehyrogenase (LDH) [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Glucose [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Urea [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Blood Urea Nitrogen [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Creatinine [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Bilirubin, Total [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Uric Acid [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Protein, Total [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Albumin [ Time Frame: Baseline to Week 48 or at premature discontinuation if before Week 48 ] [ Designated as safety issue: No ]
    Week 48 - baseline

  • Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks [ Time Frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication ] [ Designated as safety issue: No ]
    Change From Baseline in Trough Forced Expiratory Volume in 1 second (FEV1) after 2, 8, 16, 24, 32 and 40 weeks. The means are adjusted for centre, smoking status at entry and baseline value.

  • Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks [ Time Frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication ] [ Designated as safety issue: No ]
    Change From Baseline in Trough Forced vital capacity (FVC) after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.

  • Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks [ Time Frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication ] [ Designated as safety issue: No ]
    FEV1 AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.

  • Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks [ Time Frame: 10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication ] [ Designated as safety issue: No ]
    FVC AUC0-3 represents the Area under Curve over the time interval from 0 to 3 hours after 2, 8, 16, 24, 32, 40 and 48 weeks. The means are adjusted for centre, smoking status at entry and baseline value.

  • Weekly Mean Morning Pre-dose PEFRs [ Time Frame: Weeks 2, 8, 16, 24, 32, 40, 48 ] [ Designated as safety issue: No ]
    Weekly mean morning pre-dose peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.

  • Weekly Mean Morning Evening PEFRs [ Time Frame: Weeks 2, 8, 16, 24, 32, 40, 48 ] [ Designated as safety issue: No ]
    Weekly mean evening peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.

  • Weekly Mean Number of Puffs of Rescue Medication Per Day [ Time Frame: Weeks 2, 8, 16, 24, 32, 40, 48 ] [ Designated as safety issue: No ]
    Weekly mean number of puffs of rescue medication used per day as required (PRN salbutamol). The means are adjusted for centre, smoking status at entry, and baseline value.

  • Mahler TDI Scores [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

    Mahler Transitional Dyspnoea Index (TDI) scores measured as change in functional impairment, change in magnitude of tasks and change in magnitude of efforts over the treatment period. The means are adjusted for centre, smoking status at entry and baseline value.

    Worst score = -3, best score = +3


  • Saint George's Respiratory Questionnaire (SGRQ) Scores [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

    Saint George's Respiratory Questionnaire (SGRQ) Scores impacts, activities and symptoms. Worst score = 100, best score = 0.

    The means are adjusted for centre, smoking status at entry and baseline value.


  • COPD Symptoms Scores [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

    COPD symptoms Scores - wheezing, shortness of breath, coughing and tightness of chest over the treatment period.

    Scale: 0 = None, 1 = Mild, 2 = Moderate, 3 = Severe The means are adjusted for centre, smoking status at entry and baseline value.


  • PGE Scores [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Physician's Global evaluation (PGE) scores over the treatment period. Scale: 1−2 = Poor, 3−4 = Fair, 5−6 = Good, 7−8 = Excellent The means are adjusted for centre, smoking status at entry and baseline value.

  • PGR Scores [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Patient's Global rating (PGR) scores over the treatment period. Scale: 1=much better to 7=much worse The means are adjusted for centre, smoking status at entry and baseline value.


Enrollment: 1007
Study Start Date: February 2003
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Tiotropium Respimat 5mcg (Tio R5) Drug: Tiotropium Inhalation Solution
Tiotropium Respimat 10mcg (Tio R10) Drug: Tiotropium Inhalation Solution
Placebo Other: Placebo

  Eligibility

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

Criteria

  • Patients with stable moderate to severe COPD and a smoking history of at least 10 pack years were eligible for inclusion in the study. Patients with significant diseases other than COPD were excluded as were patients with a recent history of myocardial infarction, history of malignancy, unstable or life-threatening cardiac arrhythmia, narrow-angle glaucoma, asthma or other allergic conditions. Patients treated with cromolyn, nedocromil, oral beta-adrenergics or unstable doses of oral corticosteroids were ineligible for inclusion in the study as were patients who had received previous treatment with tiotropium.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00168831

  Show 78 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Study Coordinator Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00168831     History of Changes
Other Study ID Numbers: 205.255
Study First Received: September 12, 2005
Results First Received: January 30, 2009
Last Updated: May 15, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Pharmaceutical Solutions
Tiotropium
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014