Tiotropium Bromide in Cystic Fibrosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01179347
First received: August 10, 2010
Last updated: November 27, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Cystic Fibrosis
Drug: tiotropium Respimat® inhaler
Drug: Placebo Respimat® inhaler
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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).

  • Trough FEV1 Response [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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).

  • Trough FVC Response [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Pre-bronchodilator Forced Expiratory Flow Between 25 Percent and 75 Percent of the FVC (FEF25−75) Response [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With at Least 1 Pulmonary Exacerbation During Double-blind Treatment [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 464
Study Start Date: September 2010
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01179347

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

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01179347     History of Changes
Other Study ID Numbers: 205.438, 2010-019802-17
Study First Received: August 10, 2010
Results First Received: February 13, 2013
Last Updated: November 27, 2013
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Federal Office for Safety in Health Care
Belgium:
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Ireland: Irish Medicines Board
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Ethics Committee
Poland: Registration Medicinal Product Medical Device Biocidal Product
Portugal: National Pharmacy and Medicines Institute
Russia: Pharmacological Committee, Ministry of Health
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Tiotropium
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 20, 2014