Tiotropium / Respimat One-Year Study

Pulmonary Disease, Chronic Obstructive Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00168831
• Other study ID #: 205.255
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2005
• Last updated: May 15, 2014
• Start date: February 2003

Study information

• Verified date: September 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1007
• Est. primary completion date: June 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Tiotropium Inhalation Solution

Other:
• Placebo

Locations

Country	Name	City	State
Australia	Boehringer Ingelheim Investigational Site	Adelaide	South Australia
Australia	Boehringer Ingelheim Investigational Site	Garran	Australian Capital Territory
Australia	Boehringer Ingelheim Investigational Site	Nedlands	Western Australia
Austria	Boehringer Ingelheim Investigational Site	Innsbruck
Austria	Boehringer Ingelheim Investigational Site	Mittersill
Austria	Boehringer Ingelheim Investigational Site	Schwechat
Austria	Boehringer Ingelheim Investigational Site	Wels
Austria	Baumgartner Hohe Otto Wagner Spital Wien	Wien
Austria	Boehringer Ingelheim Investigational Site	Wien
Canada	Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	Boehringer Ingelheim Investigational Site	Sherbrooke	Quebec
Canada	Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba
Finland	Boehringer Ingelheim Investigational Site	Espoo
Finland	Boehringer Ingelheim Investigational Site	Helsinki
Finland	Boehringer Ingelheim Investigational Site	Lahti
Finland	Boehringer Ingelheim Investigational Site	Lappeenranta
Finland	Boehringer Ingelheim Investigational Site	Lohja
France	Boehringer Ingelheim Investigational Site	Amboise cedex
France	Boehringer Ingelheim Investigational Site	Chauny
France	Boehringer Ingelheim Investigational Site	Marseille cedex 06
France	Boehringer Ingelheim Investigational Site	Metz cedex 01
France	Boehringer Ingelheim Investigational Site	Montpellier
France	Boehringer Ingelheim Investigational Site	Nantes
Greece	Boehringer Ingelheim Investigational Site	Alexandroupolis
Greece	Boehringer Ingelheim Investigational Site	Athens
Greece	Boehringer Ingelheim Investigational Site	Mournies-Chania
Greece	Boehringer Ingelheim Investigational Site	Trikala
Ireland	Boehringer Ingelheim Investigational Site	Dublin
Ireland	Boehringer Ingelheim Investigational Site	Dublin 4
Ireland	Boehringer Ingelheim Investigational Site	Dublin 7
Italy	Boehringer Ingelheim Investigational Site	Bologna
Italy	Boehringer Ingelheim Investigational Site	Bussolengo (vr)
Italy	Boehringer Ingelheim Investigational Site	Cava dei tirreni (SA)
Italy	Boehringer Ingelheim Investigational Site	Crema (CR)
Italy	Boehringer Ingelheim Investigational Site	Genova
Italy	Boehringer Ingelheim Investigational Site	Milano
Italy	Boehringer Ingelheim Investigational Site	Pistoia
Italy	Boehringer Ingelheim Investigational Site	Roma
Italy	Boehringer Ingelheim Investigational Site	Salerno
Italy	Boehringer Ingelheim Investigational Site	Sesto San Giovanni (Milano)
Netherlands	Boehringer Ingelheim Investigational Site	Arnhem
Netherlands	Boehringer Ingelheim Investigational Site	Eindhoven
Netherlands	Boehringer Ingelheim Investigational Site	Heerenveen
Netherlands	Boehringer Ingelheim Investigational Site	Hoorn
Netherlands	Boehringer Ingelheim Investigational Site	Leeuwarden
Netherlands	Boehringer Ingelheim Investigational Site	Rotterdam
New Zealand	Boehringer Ingelheim Investigational Site	Auckland
New Zealand	Boehringer Ingelheim Investigational Site	Hamilton
Russian Federation	Boehringer Ingelheim Investigational Site	St. Petersburg
South Africa	Boehringer Ingelheim Investigational Site	Bellville
South Africa	Boehringer Ingelheim Investigational Site	Cape Town
South Africa	Boehringer Ingelheim Investigational Site	George
South Africa	Boehringer Ingelheim Investigational Site	Johannesburg
South Africa	Boehringer Ingelheim Investigational Site	Vanderbijlpark
Spain	Boehringer Ingelheim Investigational Site	Barcelona
Spain	Boehringer Ingelheim Investigational Site	Centelles
Spain	Boehringer Ingelheim Investigational Site	Murcia
Spain	Boehringer Ingelheim Investigational Site	Sant Boi de Llobregat (Barcelona)
United Kingdom	Boehringer Ingelheim Investigational Site	Babbacombe
United Kingdom	Boehringer Ingelheim Investigational Site	Cottingham
United Kingdom	Boehringer Ingelheim Investigational Site	Isleworth
United Kingdom	Boehringer Ingelheim Investigational Site	Manchester
United Kingdom	Boehringer Ingelheim Investigational Site	Plymouth
United Kingdom	Boehringer Ingelheim Investigational Site	Sunderland
United States	Boehringer Ingelheim Investigational Site	Bay Shore	New York
United States	Boehringer Ingelheim Investigational Site	Birmingham	Alabama
United States	Boehringer Ingelheim Investigational Site	Charleston	South Carolina
United States	Boehringer Ingelheim Investigational Site	Chesterfield	Missouri
United States	Boehringer Ingelheim Investigational Site	Gainesville	Florida
United States	Boehringer Ingelheim Investigational Site	Hallandale	Florida
United States	Boehringer Ingelheim Investigational Site	Hines	Illinois
United States	Boehringer Ingelheim Investigational Site	Houston	Texas
United States	Boehringer Ingelheim Investigational Site	La Jolla	California
United States	Boehringer Ingelheim Investigational Site	Long Beach	California
United States	Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	Boehringer Ingelheim Investigational Site	San Luis Obispo	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Finland,  France,  Greece,  Ireland,  Italy,  Netherlands,  New Zealand,  Russian Federation,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Trough FEV1 After 48 Weeks	Change From Baseline in Trough Forced Expiratory Volume in 1 second (FEV1) after 48 weeks	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication	No
Primary	Saint George's Respiratory Questionnaire (SGRQ) Total Score, Full Analysis Set - Saint George's Respiratory Questionnaire (FAS-QOL)	Rating scale of 3 domains - symptoms, activities and impact (weighted). Worst score = 100, best score = 0	Week 48	No
Primary	TDI Focal Score, Full Analysis Set - Transitional Dyspnoea Index (FAS-TDI) (Combined Studies)	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.	Week 48	No
Primary	COPD Exacerbation Rate, Safety Set (SS) (Combined Studies)	Number of Chronic Obstructive Pulmonary Disease (COPD) exacerbations per patient year; For this endpoint data of the twin studies NCT00168844 and NCT00168831 was combined.	48 weeks	No
Secondary	Change From Baseline in Heart Rate	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose	No
Secondary	Change From Baseline in PR Interval		Baseline to Week 40 pre-dose	No
Secondary	Change From Baseline in QRS Interval	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose	No
Secondary	Change From Baseline in QT Interval	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose	No
Secondary	Change From Baseline in QT Interval (Bazett)	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose	No
Secondary	Change From Baseline in QT Interval (Fridericia)	Week 40 pre-dose - baseline	Baseline to Week 40 pre-dose	No
Secondary	Change From Baseline in Heart Rate	Week 40 - baseline	Baseline to Week 40	No
Secondary	Change From Baseline in Supraventricular Premature Beat (SVPB) Total	Week 40 - baseline	Baseline to Week 40	No
Secondary	Change From Baseline in SVPB Run Events	Week 40 - baseline	Baseline to Week 40	No
Secondary	Change From Baseline in SVPB Pairs	Week 40 - baseline	Baseline to Week 40	No
Secondary	Change From Baseline in Ventricular Premature Beat (VPB) Total	Week 40 - baseline	Baseline to Week 40	No
Secondary	Change From Baseline in Ventricular Premature Beat (VPB) Run Events	Week 40 - baseline	Baseline to Week 40	No
Secondary	Change From Baseline in VPB Pairs	Week 40 - baseline	Baseline to Week 40	No
Secondary	Change From Baseline in Haematocrit, Packed Cell Volume (PCV)		Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Haemoglobin	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Red Blood Cell Count	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in White Blood Cell Count	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Platelets	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Neutrophils	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Eosinophils	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Basophils	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Lymphocytes	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Monocytes	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Neutrophils (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Eosinophils (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Basophils (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Lymphocytes (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Monocytes (Absolute)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Calcium	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Phosphate	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Aspartate Transaminase/Glutamic-oxaloacetic Transaminase (AST/GOT), Serum Glutamic-oxaloacetic Transaminase (SGOT)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Alanine Transaminase/Glutamic Pyruvate Transaminase (ALT/GPT), Serum Glutamate Pyruvate Transaminase (SGPT)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Alkaline Phosphatase	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Lactic Dehyrogenase (LDH)	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Glucose	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Urea	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Blood Urea Nitrogen	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Creatinine	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Bilirubin, Total	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Uric Acid	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Protein, Total	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Albumin	Week 48 - baseline	Baseline to Week 48 or at premature discontinuation if before Week 48	No
Secondary	Change From Baseline in Trough FEV1 After 2, 8, 16, 24, 32 and 40 Weeks	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.	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication	No
Secondary	Change From Baseline in Trough FVC After 2, 8, 16, 24, 32, 40 and 48 Weeks	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.	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication	No
Secondary	Change From Baseline in FEV1 AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks	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.	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication	No
Secondary	Change From Baseline in FVC AUC0-3 After 2, 8, 16, 24, 32, 40 and 48 Weeks	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.	10 minutes prior to test-drug inhalation and at 5, 30 and 60 minutes and 2 and 3 hours after inhalation of study medication	No
Secondary	Weekly Mean Morning Pre-dose PEFRs	Weekly mean morning pre-dose peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.	Weeks 2, 8, 16, 24, 32, 40, 48	No
Secondary	Weekly Mean Morning Evening PEFRs	Weekly mean evening peak expiratory flow rates (PEFRs). The means are adjusted for centre, smoking status at entry, and baseline value.	Weeks 2, 8, 16, 24, 32, 40, 48	No
Secondary	Weekly Mean Number of Puffs of Rescue Medication Per Day	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.	Weeks 2, 8, 16, 24, 32, 40, 48	No
Secondary	Mahler TDI Scores	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	Week 48	No
Secondary	Saint George's Respiratory Questionnaire (SGRQ) Scores	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.	Week 48	No
Secondary	COPD Symptoms Scores	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.	Week 48	No
Secondary	PGE Scores	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.	Week 48	No
Secondary	PGR Scores	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.	Week 48	No

External Links

•   Link
•   Link
•   Link