Tiotropium Bromide in Cystic Fibrosis

Phase 3

Completed

Conditions: Cystic Fibrosis

Interventions: Drug: tiotropium Respimat® inhaler
Drug: Placebo Respimat® inhaler

Registration Number: NCT01179347

Lead Sponsor: Boehringer Ingelheim

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 464

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
tiotropium	tiotropium Respimat® inhaler	2 inhalations once daily delivered with Respimat® inhaler
placebo	Placebo Respimat® inhaler	2 inhalations once daily delivered with Respimat® inhaler

Primary Outcome Measures

Name	Time	Method
Forced Expiratory Volume in 1 Second (FEV1) 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.	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	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.

Secondary Outcome Measures

Name	Time	Method
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.	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).
Percentage of Participants With at Least 1 Pulmonary Exacerbation During Double-blind Treatment	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.
Trough FVC Response	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.
Pre-bronchodilator Forced Expiratory Flow Between 25 Percent and 75 Percent of the FVC (FEF25-75) Response	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.
Change From Baseline in Revised Cystic Fibrosis Questionnaire (CFQ-R) Score	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.

Trial Locations

Locations (99): 205.438.01019 Boehringer Ingelheim Investigational Site
🇺🇸
Cleveland, Ohio, United States
205.438.61001 Boehringer Ingelheim Investigational Site
🇦🇺
Adelaide, South Australia, Australia
205.438.02001 Boehringer Ingelheim Investigational Site
🇨🇦
Sherbrooke, Quebec, Canada
205.438.61004 Boehringer Ingelheim Investigational Site
🇦🇺
Herston, Queensland, Australia
205.438.01021 Boehringer Ingelheim Investigational Site
🇺🇸
Orlando, Florida, United States
205.438.02005 Boehringer Ingelheim Investigational Site
🇨🇦
Calgary, Alberta, Canada
205.438.01008 Boehringer Ingelheim Investigational Site
🇺🇸
Orlando, Florida, United States
205.438.61002 Boehringer Ingelheim Investigational Site
🇦🇺
Subiaco, Western Australia, Australia
205.438.01011 Boehringer Ingelheim Investigational Site
🇺🇸
San Diego, California, United States
205.438.01007 Boehringer Ingelheim Investigational Site
🇺🇸
Indianapolis, Indiana, United States
205.438.32001 Boehringer Ingelheim Investigational Site
🇧🇪
Leuven, Belgium
205.438.35004 Boehringer Ingelheim Investigational Site
🇵🇹
Porto, Portugal
205.438.01014 Boehringer Ingelheim Investigational Site
🇺🇸
Orlando, Florida, United States
205.438.01010 Boehringer Ingelheim Investigational Site
🇺🇸
Manchester, New Hampshire, United States
205.438.01003 Boehringer Ingelheim Investigational Site
🇺🇸
Syracuse, New York, United States
205.438.43001 Boehringer Ingelheim Investigational Site
🇦🇹
Innsbruck, Austria
205.438.32002 Boehringer Ingelheim Investigational Site
🇧🇪
Bruxelles, Belgium
205.438.01004 Boehringer Ingelheim Investigational Site
🇺🇸
Tuscon, Arizona, United States
205.438.01006 Boehringer Ingelheim Investigational Site
🇺🇸
South Bend, Indiana, United States
205.438.01018 Boehringer Ingelheim Investigational Site
🇺🇸
Jacksonville, Florida, United States
205.438.49005 Boehringer Ingelheim Investigational Site
🇩🇪
Hamburg, Germany
205.438.42001 Boehringer Ingelheim Investigational Site
🇨🇿
Prague 5, Czech Republic
205.438.36004 Boehringer Ingelheim Investigational Site
🇭🇺
Szeged, Hungary
205.438.33010 Boehringer Ingelheim Investigational Site
🇫🇷
Angers, France
205.438.49001 Boehringer Ingelheim Investigational Site
🇩🇪
Bochum, Germany
205.438.49007 Boehringer Ingelheim Investigational Site
🇩🇪
Gießen, Germany
205.438.39001 Boehringer Ingelheim Investigational Site
🇮🇹
Firenze, Italy
205.438.49008 Boehringer Ingelheim Investigational Site
🇩🇪
Tübingen, Germany
205.438.97003 Boehringer Ingelheim Investigational Site
🇮🇱
Haifa, Israel
205.438.97004 Boehringer Ingelheim Investigational Site
🇮🇱
Tel Hashomer, Israel
205.438.49002 Boehringer Ingelheim Investigational Site
🇩🇪
Frankfurt, Germany
205.438.35301 Boehringer Ingelheim Investigational Site
🇮🇪
Dublin 12, Ireland
205.438.39002 Boehringer Ingelheim Investigational Site
🇮🇹
Verona, Italy
205.438.07005 Boehringer Ingelheim Investigational Site
🇷🇺
Moscow, Russian Federation
205.438.49012 Boehringer Ingelheim Investigational Site
🇩🇪
Frankfurt, Germany
205.438.42102 Boehringer Ingelheim Investigational Site
🇸🇰
Banska Bystrica, Slovakia
205.438.41004 Boehringer Ingelheim Investigational Site
🇨🇭
Bern 4, Switzerland
205.438.44005 Boehringer Ingelheim Investigational Site
🇬🇧
Nottingham, United Kingdom
205.438.34005 Boehringer Ingelheim Investigational Site
🇪🇸
Barcelona, Spain
205.438.44009 Boehringer Ingelheim Investigational Site
🇬🇧
Brighton, United Kingdom
205.438.44004 Boehringer Ingelheim Investigational Site
🇬🇧
Leeds, United Kingdom
205.438.01001 Boehringer Ingelheim Investigational Site
🇺🇸
Detroit, Michigan, United States
205.438.01013 Boehringer Ingelheim Investigational Site
🇺🇸
Oklahoma City, Oklahoma, United States
205.438.02003 Boehringer Ingelheim Investigational Site
🇨🇦
Hamilton, Ontario, Canada
205.438.33015 Boehringer Ingelheim Investigational Site
🇫🇷
Lisieux, France
205.438.33005 Boehringer Ingelheim Investigational Site
🇫🇷
Nantes, France
205.438.07004 Boehringer Ingelheim Investigational Site
🇷🇺
Voronezh, Russian Federation
205.438.01012 Boehringer Ingelheim Investigational Site
🇺🇸
Milwaukee, Wisconsin, United States
205.438.61003 Boehringer Ingelheim Investigational Site
🇦🇺
Chermside, Queensland, Australia
205.438.01005 Boehringer Ingelheim Investigational Site
🇺🇸
Charleston, South Carolina, United States
205.438.33003 Boehringer Ingelheim Investigational Site
🇫🇷
Montpellier, France
205.438.33004 Boehringer Ingelheim Investigational Site
🇫🇷
Rouen cedex, France
205.438.49003 Boehringer Ingelheim Investigational Site
🇩🇪
München, Germany
205.438.97001 Boehringer Ingelheim Investigational Site
🇮🇱
Jerusalem, Israel
205.438.32003 Boehringer Ingelheim Investigational Site
🇧🇪
Jette, Belgium
205.438.33013 Boehringer Ingelheim Investigational Site
🇫🇷
BRON Cedex, France
205.438.02007 Boehringer Ingelheim Investigational Site
🇨🇦
Vancouver, British Columbia, Canada
205.438.02006 Boehringer Ingelheim Investigational Site
🇨🇦
Toronto, Ontario, Canada
205.438.42004 Boehringer Ingelheim Investigational Site
🇨🇿
Olomouc, Czech Republic
205.438.02004 Boehringer Ingelheim Investigational Site
🇨🇦
Halifax, Nova Scotia, Canada
205.438.42003 Boehringer Ingelheim Investigational Site
🇨🇿
Brno, Czech Republic
205.438.33002 Boehringer Ingelheim Investigational Site
🇫🇷
Lille Cedex, France
205.438.33007 Boehringer Ingelheim Investigational Site
🇫🇷
Paris, France
205.438.33001 Boehringer Ingelheim Investigational Site
🇫🇷
Paris, France
205.438.33006 Boehringer Ingelheim Investigational Site
🇫🇷
Paris, France
205.438.33014 Boehringer Ingelheim Investigational Site
🇫🇷
Nice Cedex 1, France
205.438.33011 Boehringer Ingelheim Investigational Site
🇫🇷
Rennes, France
205.438.33008 Boehringer Ingelheim Investigational Site
🇫🇷
Roscoff Cedex, France
205.438.33009 Boehringer Ingelheim Investigational Site
🇫🇷
Vannes, France
205.438.49011 Boehringer Ingelheim Investigational Site
🇩🇪
Frankfurt/Main, Germany
205.438.49006 Boehringer Ingelheim Investigational Site
🇩🇪
Gerlingen, Germany
205.438.34002 Boehringer Ingelheim Investigational Site
🇪🇸
Madrid, Spain
205.438.36003 Boehringer Ingelheim Investigational Site
🇭🇺
Mosdos, Hungary
205.438.97002 Boehringer Ingelheim Investigational Site
🇮🇱
Petach Tikva, Israel
205.438.39003 Boehringer Ingelheim Investigational Site
🇮🇹
Genova, Italy
205.438.35002 Boehringer Ingelheim Investigational Site
🇵🇹
Lisboa, Portugal
205.438.35001 Boehringer Ingelheim Investigational Site
🇵🇹
Lisboa, Portugal
205.438.07001 Boehringer Ingelheim Investigational Site
🇷🇺
Moscow, Russian Federation
205.438.07003 Boehringer Ingelheim Investigational Site
🇷🇺
St. Petersburg, Russian Federation
205.438.07002 Boehringer Ingelheim Investigational Site
🇷🇺
Yaroslavl, Russian Federation
205.438.42103 Boehringer Ingelheim Investigational Site
🇸🇰
Kosice, Slovakia
205.438.27001 Boehringer Ingelheim Investigational Site
🇿🇦
Cape Town, South Africa
205.438.34001 Boehringer Ingelheim Investigational Site
🇪🇸
Madrid, Spain
205.438.34004 Boehringer Ingelheim Investigational Site
🇪🇸
Valencia, Spain
205.438.44007 Boehringer Ingelheim Investigational Site
🇬🇧
Cambridge, United Kingdom
205.438.44003 Boehringer Ingelheim Investigational Site
🇬🇧
Sheffield, United Kingdom
205.438.44002 Boehringer Ingelheim Investigational Site
🇬🇧
Plymouth, United Kingdom
205.438.41003 Boehringer Ingelheim Investigational Site
🇨🇭
Basel, Switzerland
205.438.41002 Boehringer Ingelheim Investigational Site
🇨🇭
Zürich, Switzerland
205.438.32004 Boehringer Ingelheim Investigational Site
🇧🇪
Edegem, Belgium
205.438.48002 Boehringer Ingelheim Investigational Site
🇵🇱
Rabka Zdroj, Poland
205.438.42101 Boehringer Ingelheim Investigational Site
🇸🇰
Bratislava, Slovakia
205.438.43002 Boehringer Ingelheim Investigational Site
🇦🇹
Salzburg, Austria
205.438.48003 Boehringer Ingelheim Investigational Site
🇵🇱
Warszawa, Poland
205.438.41001 Boehringer Ingelheim Investigational Site
🇨🇭
Zürich, Switzerland
205.438.48001 Boehringer Ingelheim Investigational Site
🇵🇱
Lodz, Poland
205.438.35003 Boehringer Ingelheim Investigational Site
🇵🇹
Porto, Portugal
205.438.42002 Boehringer Ingelheim Investigational Site
🇨🇿
Brno, Czech Republic
205.438.36002 Boehringer Ingelheim Investigational Site
🇭🇺
Budapest, Hungary