Tiotropium / Respimat One-Year Study

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00168844
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 at Week 48, Full Analysis Set - Clinic Spirometry (FAS-PFT) [ 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 ]
    Trough Forced Expiratory Volume in 1 second (FEV1)

  • 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

  • Holter (24-hour Period) - SVPB (Supraventricular Premature Beat) Run Events Change From Baseline in Supraventricular Premature Beat (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 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 ]
    Volume of red cells (erythrocytes) in blood, expressed as a fraction (percentage) of the total volume of blood

  • 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 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 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 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 (AST)/Glutamic-Oxaloacetic Transaminase (GOT), Serum GOT (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 (ALT)/Glutamic Pyruvic Transaminase (GPT), Serum GPT (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 Dehydrogenase (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 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 Score [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

    Patient's Global rating (PGR) score 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: 983
Study Start Date: January 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
  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: NCT00168844

  Show 73 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: NCT00168844     History of Changes
Other Study ID Numbers: 205.254
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
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Pharmaceutical Solutions
Tiotropium
Therapeutic Uses
Pharmacologic Actions
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 31, 2014