Tiotropium Bromide in Cystic Fibrosis

November 27, 2013 updated by: Boehringer Ingelheim

A Randomised, Double-blind, Placebo-controlled Parallel-group Trial to Confirm the Efficacy After 12 Weeks and the Safety of Tiotropium 5 Mcg Administered Once Daily Via the Respimat® Device in Patients With Cystic Fibrosis.

To date, there have been no formal clinical studies completed using tiotropium in CF patients. While there is a large body of evidence demonstrating the efficacy and safety of tiotropium in patients with Chronic Obstructive Pulmonary Disease (COPD), relatively little is known about its efficacy and safety in patients with a diagnosis of cystic fibrosis. Therefore, Boehringer Ingelheim proposed to profile the long acting anticholinergic tiotropium and to generate adequate clinical data for use as a bronchodilator in paediatric and adult CF. The phase III trial (205.438) is a part of the approved Paediatric Investigation Plan (PIP) agreed for Spiriva® Respimat® in Cystic Fibrosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

464

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • Chermside, Queensland, Australia
        • 205.438.61003 Boehringer Ingelheim Investigational Site
      • Herston, Queensland, Australia
        • 205.438.61004 Boehringer Ingelheim Investigational Site
    • South Australia
      • Adelaide, South Australia, Australia
        • 205.438.61001 Boehringer Ingelheim Investigational Site
    • Western Australia
      • Subiaco, Western Australia, Australia
        • 205.438.61002 Boehringer Ingelheim Investigational Site
  • Austria
      • Innsbruck, Austria
        • 205.438.43001 Boehringer Ingelheim Investigational Site
      • Salzburg, Austria
        • 205.438.43002 Boehringer Ingelheim Investigational Site
  • Belgium
      • Bruxelles, Belgium
        • 205.438.32002 Boehringer Ingelheim Investigational Site
      • Edegem, Belgium
        • 205.438.32004 Boehringer Ingelheim Investigational Site
      • Jette, Belgium
        • 205.438.32003 Boehringer Ingelheim Investigational Site
      • Leuven, Belgium
        • 205.438.32001 Boehringer Ingelheim Investigational Site
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • 205.438.02005 Boehringer Ingelheim Investigational Site
    • British Columbia
      • Vancouver, British Columbia, Canada
        • 205.438.02007 Boehringer Ingelheim Investigational Site
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • 205.438.02004 Boehringer Ingelheim Investigational Site
    • Ontario
      • Hamilton, Ontario, Canada
        • 205.438.02003 Boehringer Ingelheim Investigational Site
      • Toronto, Ontario, Canada
        • 205.438.02006 Boehringer Ingelheim Investigational Site
    • Quebec
      • Sherbrooke, Quebec, Canada
        • 205.438.02001 Boehringer Ingelheim Investigational Site
  • Czech Republic
      • Brno, Czech Republic
        • 205.438.42002 Boehringer Ingelheim Investigational Site
      • Brno, Czech Republic
        • 205.438.42003 Boehringer Ingelheim Investigational Site
      • Olomouc, Czech Republic
        • 205.438.42004 Boehringer Ingelheim Investigational Site
      • Prague 5, Czech Republic
        • 205.438.42001 Boehringer Ingelheim Investigational Site
  • France
      • Angers, France
        • 205.438.33010 Boehringer Ingelheim Investigational Site
      • BRON Cedex, France
        • 205.438.33013 Boehringer Ingelheim Investigational Site
      • Lille Cedex, France
        • 205.438.33002 Boehringer Ingelheim Investigational Site
      • Lisieux, France
        • 205.438.33015 Boehringer Ingelheim Investigational Site
      • Montpellier, France
        • 205.438.33003 Boehringer Ingelheim Investigational Site
      • Nantes, France
        • 205.438.33005 Boehringer Ingelheim Investigational Site
      • Nice Cedex 1, France
        • 205.438.33014 Boehringer Ingelheim Investigational Site
      • Paris, France
        • 205.438.33001 Boehringer Ingelheim Investigational Site
      • Paris, France
        • 205.438.33006 Boehringer Ingelheim Investigational Site
      • Paris, France
        • 205.438.33007 Boehringer Ingelheim Investigational Site
      • Rennes, France
        • 205.438.33011 Boehringer Ingelheim Investigational Site
      • Roscoff Cedex, France
        • 205.438.33008 Boehringer Ingelheim Investigational Site
      • Rouen cedex, France
        • 205.438.33004 Boehringer Ingelheim Investigational Site
      • Vannes, France
        • 205.438.33009 Boehringer Ingelheim Investigational Site
  • Germany
      • Bochum, Germany
        • 205.438.49001 Boehringer Ingelheim Investigational Site
      • Frankfurt, Germany
        • 205.438.49002 Boehringer Ingelheim Investigational Site
      • Frankfurt, Germany
        • 205.438.49012 Boehringer Ingelheim Investigational Site
      • Frankfurt/Main, Germany
        • 205.438.49011 Boehringer Ingelheim Investigational Site
      • Gerlingen, Germany
        • 205.438.49006 Boehringer Ingelheim Investigational Site
      • Gießen, Germany
        • 205.438.49007 Boehringer Ingelheim Investigational Site
      • Hamburg, Germany
        • 205.438.49005 Boehringer Ingelheim Investigational Site
      • München, Germany
        • 205.438.49003 Boehringer Ingelheim Investigational Site
      • Tübingen, Germany
        • 205.438.49008 Boehringer Ingelheim Investigational Site
  • Hungary
      • Budapest, Hungary
        • 205.438.36002 Boehringer Ingelheim Investigational Site
      • Mosdos, Hungary
        • 205.438.36003 Boehringer Ingelheim Investigational Site
      • Szeged, Hungary
        • 205.438.36004 Boehringer Ingelheim Investigational Site
  • Ireland
      • Dublin 12, Ireland
        • 205.438.35301 Boehringer Ingelheim Investigational Site
  • Israel
      • Haifa, Israel
        • 205.438.97003 Boehringer Ingelheim Investigational Site
      • Jerusalem, Israel
        • 205.438.97001 Boehringer Ingelheim Investigational Site
      • Petach Tikva, Israel
        • 205.438.97002 Boehringer Ingelheim Investigational Site
      • Tel Hashomer, Israel
        • 205.438.97004 Boehringer Ingelheim Investigational Site
  • Italy
      • Firenze, Italy
        • 205.438.39001 Boehringer Ingelheim Investigational Site
      • Genova, Italy
        • 205.438.39003 Boehringer Ingelheim Investigational Site
      • Verona, Italy
        • 205.438.39002 Boehringer Ingelheim Investigational Site
  • Poland
      • Lodz, Poland
        • 205.438.48001 Boehringer Ingelheim Investigational Site
      • Rabka Zdroj, Poland
        • 205.438.48002 Boehringer Ingelheim Investigational Site
      • Warszawa, Poland
        • 205.438.48003 Boehringer Ingelheim Investigational Site
  • Portugal
      • Lisboa, Portugal
        • 205.438.35001 Boehringer Ingelheim Investigational Site
      • Lisboa, Portugal
        • 205.438.35002 Boehringer Ingelheim Investigational Site
      • Porto, Portugal
        • 205.438.35003 Boehringer Ingelheim Investigational Site
      • Porto, Portugal
        • 205.438.35004 Boehringer Ingelheim Investigational Site
  • Russian Federation
      • Moscow, Russian Federation
        • 205.438.07001 Boehringer Ingelheim Investigational Site
      • Moscow, Russian Federation
        • 205.438.07005 Boehringer Ingelheim Investigational Site
      • St. Petersburg, Russian Federation
        • 205.438.07003 Boehringer Ingelheim Investigational Site
      • Voronezh, Russian Federation
        • 205.438.07004 Boehringer Ingelheim Investigational Site
      • Yaroslavl, Russian Federation
        • 205.438.07002 Boehringer Ingelheim Investigational Site
  • Slovakia
      • Banska Bystrica, Slovakia
        • 205.438.42102 Boehringer Ingelheim Investigational Site
      • Bratislava, Slovakia
        • 205.438.42101 Boehringer Ingelheim Investigational Site
      • Kosice, Slovakia
        • 205.438.42103 Boehringer Ingelheim Investigational Site
  • South Africa
      • Cape Town, South Africa
        • 205.438.27001 Boehringer Ingelheim Investigational Site
  • Spain
      • Barcelona, Spain
        • 205.438.34005 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 205.438.34001 Boehringer Ingelheim Investigational Site
      • Madrid, Spain
        • 205.438.34002 Boehringer Ingelheim Investigational Site
      • Valencia, Spain
        • 205.438.34004 Boehringer Ingelheim Investigational Site
  • Switzerland
      • Basel, Switzerland
        • 205.438.41003 Boehringer Ingelheim Investigational Site
      • Bern 4, Switzerland
        • 205.438.41004 Boehringer Ingelheim Investigational Site
      • Zürich, Switzerland
        • 205.438.41001 Boehringer Ingelheim Investigational Site
      • Zürich, Switzerland
        • 205.438.41002 Boehringer Ingelheim Investigational Site
  • United Kingdom
      • Brighton, United Kingdom
        • 205.438.44009 Boehringer Ingelheim Investigational Site
      • Cambridge, United Kingdom
        • 205.438.44007 Boehringer Ingelheim Investigational Site
      • Leeds, United Kingdom
        • 205.438.44004 Boehringer Ingelheim Investigational Site
      • Nottingham, United Kingdom
        • 205.438.44005 Boehringer Ingelheim Investigational Site
      • Plymouth, United Kingdom
        • 205.438.44002 Boehringer Ingelheim Investigational Site
      • Sheffield, United Kingdom
        • 205.438.44003 Boehringer Ingelheim Investigational Site
  • United States
    • Arizona
      • Tuscon, Arizona, United States
        • 205.438.01004 Boehringer Ingelheim Investigational Site
    • California
      • San Diego, California, United States
        • 205.438.01011 Boehringer Ingelheim Investigational Site
    • Florida
      • Jacksonville, Florida, United States
        • 205.438.01018 Boehringer Ingelheim Investigational Site
      • Orlando, Florida, United States
        • 205.438.01008 Boehringer Ingelheim Investigational Site
      • Orlando, Florida, United States
        • 205.438.01014 Boehringer Ingelheim Investigational Site
      • Orlando, Florida, United States
        • 205.438.01021 Boehringer Ingelheim Investigational Site
    • Indiana
      • Indianapolis, Indiana, United States
        • 205.438.01007 Boehringer Ingelheim Investigational Site
      • South Bend, Indiana, United States
        • 205.438.01006 Boehringer Ingelheim Investigational Site
    • Michigan
      • Detroit, Michigan, United States
        • 205.438.01001 Boehringer Ingelheim Investigational Site
    • New Hampshire
      • Manchester, New Hampshire, United States
        • 205.438.01010 Boehringer Ingelheim Investigational Site
    • New York
      • Syracuse, New York, United States
        • 205.438.01003 Boehringer Ingelheim Investigational Site
    • Ohio
      • Cleveland, Ohio, United States
        • 205.438.01019 Boehringer Ingelheim Investigational Site
    • Oklahoma
      • Oklahoma City, Oklahoma, United States
        • 205.438.01013 Boehringer Ingelheim Investigational Site
    • South Carolina
      • Charleston, South Carolina, United States
        • 205.438.01005 Boehringer Ingelheim Investigational Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States
        • 205.438.01012 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  1. Patients with a documented diagnosis of Cystic Fibrosis (CF) (positive sweat chloride >=60 mEq/liter, by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations.
  2. Male or female patients (children less than 12 years and adolescents >12 years).
  3. Patients >=5 years of age must be able to perform acceptable spirometric maneuvers, according to the American Thoracic Society (ATS) standards.
  4. Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) >25% of predicted values.
  5. Pre-bronchodilator FEV1 at Visit 2 must be within 15% of FEV1 at Visit 1.
  6. No evidence of respiratory tract infection and no pulmonary exacerbation requiring use of intravenous/oral/inhaled antibiotics, or oral corticosteroids within 2 weeks of screening.
  7. The patient or the patient's legally acceptable representative must be able to give informed consent.
  8. Patients who are on a cycling TOBI® regimen must have completed at least 2 cycles every other month TOBI® administration prior to the screening visit.
  9. Patients who are on daily inhaled antibiotic use must be stabilized for at least 6 weeks prior to Visit 1 (screening).
  10. Patients having previously participated in study 205.339 can also be selected.

Exclusion criteria:

  1. Patients with a known hypersensitivity to study drug
  2. Patients who have participated in another study with an Investigational drug within one month preceding the screening visit.
  3. Patients who are currently participating in another trial. Observational studies are allowed. Permission should be obtained from sponsor of other study.
  4. Patients with known relevant substance abuse, including alcohol or drug abuse.
  5. Adolescent and adult female patients who are pregnant or lactating, including females who have a positive serum pregnancy test at screening.
  6. Female patients of child bearing potential who are not using a medically approved form of contraception.
  7. Clinically significant disease or medical condition other than CF or CF-related conditions that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data. Patients with diabetes may participate if their disease is under good control prior to screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: tiotropium
2 inhalations once daily delivered with Respimat® inhaler
Drug: tiotropium Respimat® inhaler
to evaluate safety and efficacy tiotropium delivered with Respimat® inhaler compared to placebo.
Placebo Comparator: placebo
2 inhalations once daily delivered with Respimat® inhaler
Drug: Placebo Respimat® inhaler
patient to receive placebo matching active drug once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve 0-4 Hours (AUC0-4h) Response
Time Frame: 30 minutes (min) before first dosing of study drug (defined as baseline), at 1 hour (h), 2 h , 3 h, and 4 h post dosing at day 1 and at 30 min before dosing, at 1 hour, 2 h , 3 h, and 4 h post dosing after 12 weeks.
Mixed Model Repeated Measurement (MMRM) results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (<= 11, >=12), baseline and baseline-by-visit interaction. FEV1 AUC0-4h was normalised for time and was calculated using the trapezoidal rule divided by the observation time (4 h).
30 minutes (min) before first dosing of study drug (defined as baseline), at 1 hour (h), 2 h , 3 h, and 4 h post dosing at day 1 and at 30 min before dosing, at 1 hour, 2 h , 3 h, and 4 h post dosing after 12 weeks.
Trough FEV1 Response
Time Frame: Baseline and 12 weeks
MMRM results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. Trough FEV1 was defined as the pre-dose FEV1 measured just prior to the administration of randomised treatment. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (<= 11, >=12), baseline and baseline-by-visit interaction.
Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Forced Vital Capacity (FVC) Area Under the Curve 0-4 Hours (AUC0-4h) Response
Time Frame: 30 minutes (min) before first dosing of study drug (defined as baseline), at 1 hour (h), 2 h , 3 h, and 4 h post dosing at day 1 and at 30 min before dosing, at 1 hour, 2 h , 3 h, and 4 h post dosing after 12 weeks.
MMRM results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (<= 11, >=12), baseline and baseline-by-visit interaction. FVC AUC0-4h was normalised for time and was calculated using the trapezoidal rule divided by the observation time (4 h).
30 minutes (min) before first dosing of study drug (defined as baseline), at 1 hour (h), 2 h , 3 h, and 4 h post dosing at day 1 and at 30 min before dosing, at 1 hour, 2 h , 3 h, and 4 h post dosing after 12 weeks.
Trough FVC Response
Time Frame: Baseline and 12 weeks
MMRM results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. Trough FCV was defined as the pre-dose FVC measured just prior to the administration of randomised treatment. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (<= 11, >=12), baseline and baseline-by-visit interaction.
Baseline and 12 weeks
Pre-bronchodilator Forced Expiratory Flow Between 25 Percent and 75 Percent of the FVC (FEF25-75) Response
Time Frame: Baseline and 12 weeks
MMRM results. Response was defined as change from baseline in percent of predicted at the end of 12-week double-blind treatment period and is therefore expressed in percent of predicted. FEF25-75 is also known as maximum mid-expiratory flow and was measured before bronchodilator (salbutamol) use. Means are adjusted for treatment, visit, treatment-by-visit interaction, age group (<= 11, >=12), baseline and baseline-by-visit interaction.
Baseline and 12 weeks
Percentage of Participants With at Least 1 Pulmonary Exacerbation During Double-blind Treatment
Time Frame: 12 weeks
Selected questions from the Respiratory and Systemic Symptoms Questionnaire (RSSQ), the investigator assessment of physical findings and pulmonary function, and the use of intravenous antibiotics as a concomitant therapy were used to determine if a cystic fibrosis-related pulmonary exacerbation had occurred.
12 weeks
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score
Time Frame: Baseline and 12 weeks
Different format of CFQ-R are used depending of the patients' age. Adolescent and adult format of CFQ-R is used for patients of 14 years and older, for younger children a parent version and a children format is used. In case parent and children questionnaires were filled out, the children questionnaire is taken into account. Scores were calculated for each domain of the CFQ-R which are presented separately. A score of 100 corresponds to the highest quality of life possible, whereas a score of 0 corresponds to the lowest quality of life possible. Increasing score indicates better health.
Baseline and 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2010

Primary Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

August 10, 2010

First Submitted That Met QC Criteria

August 10, 2010

First Posted (Estimate)

August 11, 2010

Study Record Updates

Last Update Posted (Estimate)

December 24, 2013

Last Update Submitted That Met QC Criteria

November 27, 2013

Last Verified

October 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 205.438
  • 2010-019802-17 (EudraCT Number: EudraCT)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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