Safety and Efficacy of 12-wk Treatment With Two Doses of Tiotropium Respimat in Cystic Fibrosis

Study Description

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Brief Summary:

This study evaluates the effects of 12-week treatment with two doses of tiotropium bromide (2.5 mcg q.d. and 5 mcg q.d.) compared to placebo administered via the Respimat device on lung function in patients with Cystic Fibrosis. The selection of the optimal dose will be based on bronchodilator efficacy, safety evaluations and pharmacokinetic evaluations

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: Placebo Respimat; Drug: Tiotropium bromide 5 mcg; Drug: tiotropium bromide-low dose-2.5mcg	Phase 2

Expanded Access : Boehringer Ingelheim has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	510 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double
Primary Purpose:	Treatment
Official Title:	A Randomized, Double-blind, Placebo-controlled Parallel Group Study to Investigate the Safety and Efficacy of Two Doses of Tiotropium Bromide (2.5 mcg and 5 mcg) Administered Once Daily Via the Respimat Device for 12 Weeks in Patients With Cystic Fibrosis.
Study Start Date :	September 2008
Actual Primary Completion Date :	April 2010

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Tiotropium Respimat 2.5 mcg; patient to receive low dose tiotropium once daily	Drug: tiotropium bromide-low dose-2.5mcg; patient to receive low dose tiotropium once daily
Experimental: Tiotropium Respimat 5 mcg; patient to receive high dose tiotropium once daily	Drug: Tiotropium bromide 5 mcg; patient to recieve high dose tiotropium once daily
Placebo Comparator: Placebo Respimat; patient to receive placebo once daily	Drug: Placebo Respimat; patient to receive placebo matching active drug once daily

Outcome Measures

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Primary Outcome Measures :

1. Percent Predicted FEV1 AUC0-4 Response at the End of Week 12 [ Time Frame: Baseline, Week 12 ]
   Outcome measure description: Change from baseline in percent predicted Forced Expiratory Volume in one second (FEV1) Area Under the Curve from 0 to 4 hours (AUC0-4). Calculated as percent predicted at week 12 minus percent predicted at baseline.
2. Percent Predicted FEV1 Trough Response at the End of Week 12 [ Time Frame: Baseline, Week 12 ]
   Outcome measure description: Change from baseline in percent predicted trough Forced Expiratory Volume in one second. Calculated as percent predicted at week 12 minus percent predicted at baseline.

Secondary Outcome Measures :

1. Percent Predicted FVC AUC0-4 Response at the End of Week 12 [ Time Frame: Baseline, Week 12 ]
   Change from baseline in percent predicted Forced Vital Capacity (FVC) Area Under the Curve from 0 to 4 hours (AUC0-4). Calculated as percent predicted at week 12 minus percent predicted at baseline.
2. Percent Predicted FVC Trough Response at the End of Week 12 [ Time Frame: Baseline, Week 12 ]
   Change from baseline in percent predicted trough Forced Vital Capacity (FVC). Calculated as percent predicted at week 12 minus percent predicted at baseline.
3. Pre-bronchodilator FEF25-75 Percent Predicted at the End of Week 12 [ Time Frame: Baseline, Week 12 ]
   Forced Expiratory Flow at 25-75% of vital capacity (FEF25-75). Calculated as percent predicted at week 12 minus percent predicted at baseline.
4. Change From Baseline in Residual Volume/Total Lung Capacity (RV/TLC) at the End of Week 12 [ Time Frame: Baseline, Week 12 ]
   Change from baseline in static lung hyperinflation as measured by RV/TLC. Calculated as percent predicted at week 12 minus percent predicted at baseline.
5. Respiratory and Systemic Symptoms Questionnaire (RSSQ) [ Time Frame: 12 weeks ]
   Outcome measure description: The RSSQ questionnaire is used to determine the presence or absence of an exacerbation during the recall period.
6. Change From Baseline in CFQ Scores - Adult Group [ Time Frame: 12 weeks ]
   The Cystic Fibrosis questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adults with CF. This validation questionnaire consists of 50 items on generic and disease-specific scales. The scores range from 0 to 100, with higher scores indicating better health.
7. Change From Baseline in CFQ Scores - Adolescents Group [ Time Frame: 12 weeks ]
   The Cystic Fibrosis questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents (age 6-13) with CF. This validation questionnaire consists of 50 items on generic and disease-specific scales. The scores range from 0 to 100, with higher scores indicating better health.
8. Change From Baseline in CFQ Scores - Parent Questionnaire [ Time Frame: 12 weeks ]
   The Cystic Fibrosis questionnaire (CFQ) is a disease-specific instrument that measures health-related quality of life (HRQOL) for adolescents with CF - parent questionnaire. This validation questionnaire consists of 50 items on generic and disease-specific scales. The scores range from 0 to 100, with higher scores indicating better health.
9. Amount of Tiotropium Eliminated in Urine From 0 to 4 Hours at Steady State (Ae0-4,ss) [ Time Frame: pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dose ]
   Ae0-4,ss represents the amount of tiotropium that is eliminated in urine from time 0 to 4 hours at steady state
10. Maximum Measured Concentration at Steady State (Cmax,ss) [ Time Frame: pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dose ]
    Cmax,ss represents the maximum measured concentration of tiotropium in plasma at steady state.
11. Time From Dosing to the Maximum Concentration (Tmax,ss) [ Time Frame: pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dose ]
    Tmax,ss represents the time from dosing to the maximum concentration of tiotropium in plasma
12. Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation [ Time Frame: From first drug administration until 30 days after last drug administration (up to 121 days) ]
    Clinical Relevant Abnormalities for Vital Signs and Laboratory evaluation. Any new or clinically relevant worsening of baseline conditions was reported as Adverse Event.

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion criteria:

1. Male or female patients
2. Diagnosis of Cystic Fibrosis (positive sweat chloride test or two identifiable mutations)
3. Pre-bronchodilator FEV1 greater/equal 25% of predicted values

Exclusion criteria:

1. Significant history of allergy/hypersensitivity
2. Hypersensitivity to study drug
3. Participation in another trial
4. Female patients who are pregnant or lactating
5. Female patients of childbearing potential
6. Patients who have started a new medication for CF within 4 weeks of screening
7. Patients with known substance abuse
8. Clinically significant disease other than CF

Contacts and Locations

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Sponsors and Collaborators

Boehringer Ingelheim

Investigators

Study Chair:	Boehringer Ingelheim	Boehringer Ingelheim

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Bradley JM, Koker P, Deng Q, Moroni-Zentgraf P, Ratjen F, Geller DE, Elborn JS; Tiotropium Cystic Fibrosis Study Group. Testing two different doses of tiotropium Respimat® in cystic fibrosis: phase 2 randomized trial results. PLoS One. 2014 Sep 4;9(9):e106195. doi: 10.1371/journal.pone.0106195. eCollection 2014.

Responsible Party:	Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier:	NCT00737100 History of Changes
Other Study ID Numbers:	205.339; 2008-001156-43 ( EudraCT Number: EudraCT )
First Posted:	August 18, 2008
Results First Posted:	April 13, 2011
Last Update Posted:	May 16, 2014
Last Verified:	January 2014

Additional relevant MeSH terms:

Fibrosis; Cystic Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Tiotropium Bromide; Bromides; Bronchodilator Agents	Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Parasympatholytics; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anticonvulsants