Tiotropium Bromide in Cystic Fibrosis

NCT01179347 | Completed Phase 3 Results

• 2 other identifiers: 205.4382010-019802-17
• Study Type: interventional
• Target: 464
• Locations: 19 countries
• Sites: 97

Brief Summary

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

• Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve 0-4 Hours (AUC0-4h) Response

  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

  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 Outcomes (5)

• Forced Vital Capacity (FVC) Area Under the Curve 0-4 Hours (AUC0-4h) Response

  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

  Baseline and 12 weeks

• Pre-bronchodilator Forced Expiratory Flow Between 25 Percent and 75 Percent of the FVC (FEF25-75) Response

  Baseline and 12 weeks

• Percentage of Participants With at Least 1 Pulmonary Exacerbation During Double-blind Treatment

  12 weeks

• Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score

  Baseline and 12 weeks

Study Arms (2)

tiotropium

EXPERIMENTAL

2 inhalations once daily delivered with Respimat® inhaler

Drug: tiotropium Respimat® inhaler

placebo

PLACEBO COMPARATOR

2 inhalations once daily delivered with Respimat® inhaler

Drug: Placebo Respimat® inhaler

Interventions

tiotropium Respimat® inhaler DRUG

to evaluate safety and efficacy tiotropium delivered with Respimat® inhaler compared to placebo.

tiotropium

Placebo Respimat® inhaler DRUG

patient to receive placebo matching active drug once daily

placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female patients (children less than 12 years and adolescents \>12 years).
• Patients \>=5 years of age must be able to perform acceptable spirometric maneuvers, according to the American Thoracic Society (ATS) standards.
• Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) \>25% of predicted values.
• Pre-bronchodilator FEV1 at Visit 2 must be within 15% of FEV1 at Visit 1.
• 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.
• The patient or the patient's legally acceptable representative must be able to give informed consent.
• 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.
• Patients who are on daily inhaled antibiotic use must be stabilized for at least 6 weeks prior to Visit 1 (screening).
• Patients having previously participated in study 205.339 can also be selected.

You may not qualify if:

• Patients with a known hypersensitivity to study drug
• Patients who have participated in another study with an Investigational drug within one month preceding the screening visit.
• Patients who are currently participating in another trial. Observational studies are allowed. Permission should be obtained from sponsor of other study.
• Patients with known relevant substance abuse, including alcohol or drug abuse.
• Adolescent and adult female patients who are pregnant or lactating, including females who have a positive serum pregnancy test at screening.
• Female patients of child bearing potential who are not using a medically approved form of contraception.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (99)

205.438.01004 Boehringer Ingelheim Investigational Site

Tuscon, Arizona, United States

Location

205.438.01011 Boehringer Ingelheim Investigational Site

San Diego, California, United States

Location

205.438.01018 Boehringer Ingelheim Investigational Site

Jacksonville, Florida, United States

Location

205.438.01008 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

Location

205.438.01014 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

Location

205.438.01021 Boehringer Ingelheim Investigational Site

Orlando, Florida, United States

Location

205.438.01007 Boehringer Ingelheim Investigational Site

Indianapolis, Indiana, United States

Location

205.438.01006 Boehringer Ingelheim Investigational Site

South Bend, Indiana, United States

Location

205.438.01001 Boehringer Ingelheim Investigational Site

Detroit, Michigan, United States

Location

205.438.01010 Boehringer Ingelheim Investigational Site

Manchester, New Hampshire, United States

Location

205.438.01003 Boehringer Ingelheim Investigational Site

Syracuse, New York, United States

Location

205.438.01019 Boehringer Ingelheim Investigational Site

Cleveland, Ohio, United States

Location

205.438.01013 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

Location

205.438.01005 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

205.438.01012 Boehringer Ingelheim Investigational Site

Milwaukee, Wisconsin, United States

Location

205.438.61003 Boehringer Ingelheim Investigational Site

Chermside, Queensland, Australia

Location

205.438.61004 Boehringer Ingelheim Investigational Site

Herston, Queensland, Australia

Location

205.438.61001 Boehringer Ingelheim Investigational Site

Adelaide, South Australia, Australia

Location

205.438.61002 Boehringer Ingelheim Investigational Site

Subiaco, Western Australia, Australia

Location

205.438.43001 Boehringer Ingelheim Investigational Site

Innsbruck, Austria

Location

205.438.43002 Boehringer Ingelheim Investigational Site

Salzburg, Austria

Location

205.438.32002 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

205.438.32004 Boehringer Ingelheim Investigational Site

Edegem, Belgium

Location

205.438.32003 Boehringer Ingelheim Investigational Site

Jette, Belgium

Location

205.438.32001 Boehringer Ingelheim Investigational Site

Leuven, Belgium

Location

205.438.02005 Boehringer Ingelheim Investigational Site

Calgary, Alberta, Canada

Location

205.438.02007 Boehringer Ingelheim Investigational Site

Vancouver, British Columbia, Canada

Location

205.438.02004 Boehringer Ingelheim Investigational Site

Halifax, Nova Scotia, Canada

Location

205.438.02003 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

205.438.02006 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

205.438.02001 Boehringer Ingelheim Investigational Site

Sherbrooke, Quebec, Canada

Location

205.438.42002 Boehringer Ingelheim Investigational Site

Brno, Czechia

Location

205.438.42003 Boehringer Ingelheim Investigational Site

Brno, Czechia

Location

205.438.42004 Boehringer Ingelheim Investigational Site

Olomouc, Czechia

Location

205.438.42001 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

205.438.33010 Boehringer Ingelheim Investigational Site

Angers, France

Location

205.438.33013 Boehringer Ingelheim Investigational Site

Bron, France

Location

205.438.33002 Boehringer Ingelheim Investigational Site

Lille, France

Location

205.438.33015 Boehringer Ingelheim Investigational Site

Lisieux, France

Location

205.438.33003 Boehringer Ingelheim Investigational Site

Montpellier, France

Location

205.438.33005 Boehringer Ingelheim Investigational Site

Nantes, France

Location

205.438.33014 Boehringer Ingelheim Investigational Site

Nice, France

Location

205.438.33001 Boehringer Ingelheim Investigational Site

Paris, France

Location

205.438.33006 Boehringer Ingelheim Investigational Site

Paris, France

Location

205.438.33007 Boehringer Ingelheim Investigational Site

Paris, France

Location

205.438.33011 Boehringer Ingelheim Investigational Site

Rennes, France

Location

205.438.33008 Boehringer Ingelheim Investigational Site

Roscoff, France

Location

205.438.33004 Boehringer Ingelheim Investigational Site

Rouen, France

Location

205.438.33009 Boehringer Ingelheim Investigational Site

Vannes, France

Location

205.438.49001 Boehringer Ingelheim Investigational Site

Bochum, Germany

Location

205.438.49002 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

205.438.49012 Boehringer Ingelheim Investigational Site

Frankfurt, Germany

Location

205.438.49011 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

205.438.49006 Boehringer Ingelheim Investigational Site

Gerlingen, Germany

Location

205.438.49007 Boehringer Ingelheim Investigational Site

Giessen, Germany

Location

205.438.49005 Boehringer Ingelheim Investigational Site

Hamburg, Germany

Location

205.438.49003 Boehringer Ingelheim Investigational Site

München, Germany

Location

205.438.49008 Boehringer Ingelheim Investigational Site

Tübingen, Germany

Location

205.438.36002 Boehringer Ingelheim Investigational Site

Budapest, Hungary

Location

205.438.36003 Boehringer Ingelheim Investigational Site

Mosdós, Hungary

Location

205.438.36004 Boehringer Ingelheim Investigational Site

Szeged, Hungary

Location

205.438.35301 Boehringer Ingelheim Investigational Site

Dublin, Ireland

Location

205.438.97003 Boehringer Ingelheim Investigational Site

Haifa, Israel

Location

205.438.97001 Boehringer Ingelheim Investigational Site

Jerusalem, Israel

Location

205.438.97002 Boehringer Ingelheim Investigational Site

Petah Tikva, Israel

Location

205.438.97004 Boehringer Ingelheim Investigational Site

Tel Litwinsky, Israel

Location

205.438.39001 Boehringer Ingelheim Investigational Site

Florence, Italy

Location

205.438.39003 Boehringer Ingelheim Investigational Site

Genova, Italy

Location

205.438.39002 Boehringer Ingelheim Investigational Site

Verona, Italy

Location

205.438.48001 Boehringer Ingelheim Investigational Site

Lodz, Poland

Location

205.438.48002 Boehringer Ingelheim Investigational Site

Rabka-Zdrój, Poland

Location

205.438.48003 Boehringer Ingelheim Investigational Site

Warsaw, Poland

Location

205.438.35001 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

205.438.35002 Boehringer Ingelheim Investigational Site

Lisbon, Portugal

Location

205.438.35003 Boehringer Ingelheim Investigational Site

Porto, Portugal

Location

205.438.35004 Boehringer Ingelheim Investigational Site

Porto, Portugal

Location

205.438.07001 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.438.07005 Boehringer Ingelheim Investigational Site

Moscow, Russia

Location

205.438.07003 Boehringer Ingelheim Investigational Site

Saint Petersburg, Russia

Location

205.438.07004 Boehringer Ingelheim Investigational Site

Voronezh, Russia

Location

205.438.07002 Boehringer Ingelheim Investigational Site

Yaroslavl, Russia

Location

205.438.42102 Boehringer Ingelheim Investigational Site

Banská Bystrica, Slovakia

Location

205.438.42101 Boehringer Ingelheim Investigational Site

Bratislava, Slovakia

Location

205.438.42103 Boehringer Ingelheim Investigational Site

Košice, Slovakia

Location

205.438.27001 Boehringer Ingelheim Investigational Site

Cape Town, South Africa

Location

205.438.34005 Boehringer Ingelheim Investigational Site

Barcelona, Spain

Location

205.438.34001 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

205.438.34002 Boehringer Ingelheim Investigational Site

Madrid, Spain

Location

205.438.34004 Boehringer Ingelheim Investigational Site

Valencia, Spain

Location

205.438.41003 Boehringer Ingelheim Investigational Site

Basel, Switzerland

Location

205.438.41004 Boehringer Ingelheim Investigational Site

Bern, Switzerland

Location

205.438.41001 Boehringer Ingelheim Investigational Site

Zurich, Switzerland

Location

205.438.41002 Boehringer Ingelheim Investigational Site

Zurich, Switzerland

Location

205.438.44009 Boehringer Ingelheim Investigational Site

Brighton, United Kingdom

Location

205.438.44007 Boehringer Ingelheim Investigational Site

Cambridge, United Kingdom

Location

205.438.44004 Boehringer Ingelheim Investigational Site

Leeds, United Kingdom

Location

205.438.44005 Boehringer Ingelheim Investigational Site

Nottingham, United Kingdom

Location

205.438.44002 Boehringer Ingelheim Investigational Site

Plymouth, United Kingdom

Location

205.438.44003 Boehringer Ingelheim Investigational Site

Sheffield, United Kingdom

Location

Related Publications (1)

• Ratjen F, Koker P, Geller DE, Langellier-Cocteaux B, Le Maulf F, Kattenbeck S, Moroni-Zentgraf P, Elborn JS; Tiotropium Cystic Fibrosis Study Group. Tiotropium Respimat in cystic fibrosis: Phase 3 and Pooled phase 2/3 randomized trials. J Cyst Fibros. 2015 Sep;14(5):608-14. doi: 10.1016/j.jcf.2015.03.004. Epub 2015 Mar 26.

  PMID: 25819269 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2010
• First Posted: August 11, 2010
• Study Start: September 1, 2010
• Primary Completion: March 1, 2012
• Last Updated: December 24, 2013
• Results First Posted: March 26, 2013

Record last verified: 2013-10

Locations

AU (4); HU (3); CZ (4); FR (14); PL (3); US (15); SL (3); CH (4); GB (6); BE (4); IE (1); ES (4); IT (3); PT (4); IL (4); RU (5); DE (9); ZA (1); CA (6)