Clinical trial NCT01179347: Tiotropium Bromide in Cystic Fibrosis
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-08-11
Enrollment: 464
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve 0-4 Hours (AUC0-4h) Response
timeFrame: 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.
measure: Trough FEV1 Response
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Forced Vital Capacity (FVC) Area Under the Curve 0-4 Hours (AUC0-4h) Response
timeFrame: 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.
measure: Trough FVC Response
timeFrame: Baseline and 12 weeks
measure: Pre-bronchodilator Forced Expiratory Flow Between 25 Percent and 75 Percent of the FVC (FEF25-75) Response
timeFrame: Baseline and 12 weeks
measure: Percentage of Participants With at Least 1 Pulmonary Exacerbation During Double-blind Treatment
timeFrame: 12 weeks
measure: Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Tuscon
country: United States
facility: 205.438.01004 Boehringer Ingelheim Investigational Site
state: Arizona
city: San Diego
country: United States
facility: 205.438.01011 Boehringer Ingelheim Investigational Site
state: California
city: Jacksonville
country: United States
facility: 205.438.01018 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 205.438.01008 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 205.438.01014 Boehringer Ingelheim Investigational Site
state: Florida
city: Orlando
country: United States
facility: 205.438.01021 Boehringer Ingelheim Investigational Site
state: Florida
city: Indianapolis
country: United States
facility: 205.438.01007 Boehringer Ingelheim Investigational Site
state: Indiana
city: South Bend
country: United States
facility: 205.438.01006 Boehringer Ingelheim Investigational Site
state: Indiana
city: Detroit
country: United States
facility: 205.438.01001 Boehringer Ingelheim Investigational Site
state: Michigan
city: Manchester
country: United States
facility: 205.438.01010 Boehringer Ingelheim Investigational Site
state: New Hampshire
city: Syracuse
country: United States
facility: 205.438.01003 Boehringer Ingelheim Investigational Site
state: New York
city: Cleveland
country: United States
facility: 205.438.01019 Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: 205.438.01013 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Charleston
country: United States
facility: 205.438.01005 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Milwaukee
country: United States
facility: 205.438.01012 Boehringer Ingelheim Investigational Site
state: Wisconsin
city: Chermside
country: Australia
facility: 205.438.61003 Boehringer Ingelheim Investigational Site
state: Queensland
city: Herston
country: Australia
facility: 205.438.61004 Boehringer Ingelheim Investigational Site
state: Queensland
city: Adelaide
country: Australia
facility: 205.438.61001 Boehringer Ingelheim Investigational Site
state: South Australia
city: Subiaco
country: Australia
facility: 205.438.61002 Boehringer Ingelheim Investigational Site
state: Western Australia
city: Innsbruck
country: Austria
facility: 205.438.43001 Boehringer Ingelheim Investigational Site
city: Salzburg
country: Austria
facility: 205.438.43002 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 205.438.32002 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 205.438.32004 Boehringer Ingelheim Investigational Site
city: Jette
country: Belgium
facility: 205.438.32003 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 205.438.32001 Boehringer Ingelheim Investigational Site
city: Calgary
country: Canada
facility: 205.438.02005 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 205.438.02007 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Halifax
country: Canada
facility: 205.438.02004 Boehringer Ingelheim Investigational Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: 205.438.02003 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 205.438.02006 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sherbrooke
country: Canada
facility: 205.438.02001 Boehringer Ingelheim Investigational Site
state: Quebec
city: Brno
country: Czech Republic
facility: 205.438.42002 Boehringer Ingelheim Investigational Site
city: Brno
country: Czech Republic
facility: 205.438.42003 Boehringer Ingelheim Investigational Site
city: Olomouc
country: Czech Republic
facility: 205.438.42004 Boehringer Ingelheim Investigational Site
city: Prague 5
country: Czech Republic
facility: 205.438.42001 Boehringer Ingelheim Investigational Site
city: Angers
country: France
facility: 205.438.33010 Boehringer Ingelheim Investigational Site
city: BRON Cedex
country: France
facility: 205.438.33013 Boehringer Ingelheim Investigational Site
city: Lille Cedex
country: France
facility: 205.438.33002 Boehringer Ingelheim Investigational Site
city: Lisieux
country: France
facility: 205.438.33015 Boehringer Ingelheim Investigational Site
city: Montpellier
country: France
facility: 205.438.33003 Boehringer Ingelheim Investigational Site
city: Nantes
country: France
facility: 205.438.33005 Boehringer Ingelheim Investigational Site
city: Nice Cedex 1
country: France
facility: 205.438.33014 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 205.438.33001 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 205.438.33006 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 205.438.33007 Boehringer Ingelheim Investigational Site
city: Rennes
country: France
facility: 205.438.33011 Boehringer Ingelheim Investigational Site
city: Roscoff Cedex
country: France
facility: 205.438.33008 Boehringer Ingelheim Investigational Site
city: Rouen cedex
country: France
facility: 205.438.33004 Boehringer Ingelheim Investigational Site
city: Vannes
country: France
facility: 205.438.33009 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 205.438.49001 Boehringer Ingelheim Investigational Site
city: Frankfurt/Main
country: Germany
facility: 205.438.49011 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 205.438.49002 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 205.438.49012 Boehringer Ingelheim Investigational Site
city: Gerlingen
country: Germany
facility: 205.438.49006 Boehringer Ingelheim Investigational Site
city: Gießen
country: Germany
facility: 205.438.49007 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 205.438.49005 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 205.438.49003 Boehringer Ingelheim Investigational Site
city: Tübingen
country: Germany
facility: 205.438.49008 Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: 205.438.36002 Boehringer Ingelheim Investigational Site
city: Mosdos
country: Hungary
facility: 205.438.36003 Boehringer Ingelheim Investigational Site
city: Szeged
country: Hungary
facility: 205.438.36004 Boehringer Ingelheim Investigational Site
city: Dublin 12
country: Ireland
facility: 205.438.35301 Boehringer Ingelheim Investigational Site
city: Haifa
country: Israel
facility: 205.438.97003 Boehringer Ingelheim Investigational Site
city: Jerusalem
country: Israel
facility: 205.438.97001 Boehringer Ingelheim Investigational Site
city: Petach Tikva
country: Israel
facility: 205.438.97002 Boehringer Ingelheim Investigational Site
city: Tel Hashomer
country: Israel
facility: 205.438.97004 Boehringer Ingelheim Investigational Site
city: Firenze
country: Italy
facility: 205.438.39001 Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: 205.438.39003 Boehringer Ingelheim Investigational Site
city: Verona
country: Italy
facility: 205.438.39002 Boehringer Ingelheim Investigational Site
city: Lodz
country: Poland
facility: 205.438.48001 Boehringer Ingelheim Investigational Site
city: Rabka Zdroj
country: Poland
facility: 205.438.48002 Boehringer Ingelheim Investigational Site
city: Warszawa
country: Poland
facility: 205.438.48003 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 205.438.35001 Boehringer Ingelheim Investigational Site
city: Lisboa
country: Portugal
facility: 205.438.35002 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 205.438.35003 Boehringer Ingelheim Investigational Site
city: Porto
country: Portugal
facility: 205.438.35004 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.438.07001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 205.438.07005 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 205.438.07003 Boehringer Ingelheim Investigational Site
city: Voronezh
country: Russian Federation
facility: 205.438.07004 Boehringer Ingelheim Investigational Site
city: Yaroslavl
country: Russian Federation
facility: 205.438.07002 Boehringer Ingelheim Investigational Site
city: Banska Bystrica
country: Slovakia
facility: 205.438.42102 Boehringer Ingelheim Investigational Site
city: Bratislava
country: Slovakia
facility: 205.438.42101 Boehringer Ingelheim Investigational Site
city: Kosice
country: Slovakia
facility: 205.438.42103 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 205.438.27001 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 205.438.34005 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 205.438.34001 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 205.438.34002 Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: 205.438.34004 Boehringer Ingelheim Investigational Site
city: Basel
country: Switzerland
facility: 205.438.41003 Boehringer Ingelheim Investigational Site
city: Bern 4
country: Switzerland
facility: 205.438.41004 Boehringer Ingelheim Investigational Site
city: Zürich
country: Switzerland
facility: 205.438.41001 Boehringer Ingelheim Investigational Site
city: Zürich
country: Switzerland
facility: 205.438.41002 Boehringer Ingelheim Investigational Site
city: Brighton
country: United Kingdom
facility: 205.438.44009 Boehringer Ingelheim Investigational Site
city: Cambridge
country: United Kingdom
facility: 205.438.44007 Boehringer Ingelheim Investigational Site
city: Leeds
country: United Kingdom
facility: 205.438.44004 Boehringer Ingelheim Investigational Site
city: Nottingham
country: United Kingdom
facility: 205.438.44005 Boehringer Ingelheim Investigational Site
city: Plymouth
country: United Kingdom
facility: 205.438.44002 Boehringer Ingelheim Investigational Site
city: Sheffield
country: United Kingdom
facility: 205.438.44003 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.