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

Study Overview
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Brief Summary
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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

Official Title
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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.

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Placebo Respimat
* Drug: Tiotropium bromide 5 mcg
* Drug: tiotropium bromide-low dose-2.5mcg


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female patients Diagnosis of Cystic Fibrosis (positive sweat chloride test or two identifiable mutations) Pre-bronchodilator FEV1 greater/equal 25% of predicted values Exclusion criteria: Significant history of allergy/hypersensitivity Hypersensitivity to study drug Participation in another trial Female patients who are pregnant or lactating Female patients of childbearing potential Patients who have started a new medication for CF within 4 weeks of screening Patients with known substance abuse Clinically significant disease other than CF
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tiotropium Respimat 2.5 mcg<br>patient to receive low dose tiotropium once daily | Drug: tiotropium bromide-low dose-2.5mcg<br>* patient to receive low dose tiotropium once daily<br>|
| Experimental: Tiotropium Respimat 5 mcg<br>patient to receive high dose tiotropium once daily | Drug: Tiotropium bromide 5 mcg<br>* patient to recieve high dose tiotropium once daily<br>|
| Placebo Comparator: Placebo Respimat<br>patient to receive placebo once daily | Drug: Placebo Respimat<br>* patient to receive placebo matching active drug once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Predicted FEV1 AUC0-4 Response at the End of 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. | Baseline, Week 12 | 
| Percent Predicted FEV1 Trough Response at the End of 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. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Predicted FVC AUC0-4 Response at the End of 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. | Baseline, Week 12 | 
| Percent Predicted FVC Trough Response at the End of 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. | Baseline, Week 12 | 
| Pre-bronchodilator FEF25-75 Percent Predicted at the End of 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. | Baseline, Week 12 | 
| Change From Baseline in Residual Volume/Total Lung Capacity (RV/TLC) at the End of 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. | Baseline, Week 12 | 
| Respiratory and Systemic Symptoms Questionnaire (RSSQ) | Outcome measure description: The RSSQ questionnaire is used to determine the presence or absence of an exacerbation during the recall period. | 12 weeks | 
| Change From Baseline in CFQ Scores - Adult Group | 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. | 12 weeks | 
| Change From Baseline in CFQ Scores - Adolescents Group | 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. | 12 weeks | 
| Change From Baseline in CFQ Scores - Parent Questionnaire | 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. | 12 weeks | 
| Amount of Tiotropium Eliminated in Urine From 0 to 4 Hours at Steady State (Ae0-4,ss) | Ae0-4,ss represents the amount of tiotropium that is eliminated in urine from time 0 to 4 hours at steady state | pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dose | 
| Maximum Measured Concentration at Steady State (Cmax,ss) | Cmax,ss represents the maximum measured concentration of tiotropium in plasma at steady state. | pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dose | 
| Time From Dosing to the Maximum Concentration (Tmax,ss) | Tmax,ss represents the time from dosing to the maximum concentration of tiotropium in plasma | pre-dose, and 5 minutes (min), 20 min, 1 hour (h), and 2 h post-dose | 
| Clinical Relevant Abnormalities for Vital Signs and Laboratory Evaluation | Clinical Relevant Abnormalities for Vital Signs and Laboratory evaluation. Any new or clinically relevant worsening of baseline conditions was reported as Adverse Event. | From first drug administration until 30 days after last drug administration (up to 121 days) |