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

Purpose

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	Intervention	Phase
Cystic Fibrosis	Drug: Placebo Respimat Drug: Tiotropium bromide 5 mcg Drug: tiotropium bromide-low dose-2.5mcg	Phase 2

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


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double-Blind 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.

Resource links provided by NLM:

Genetics Home Reference related topics: cystic fibrosis

MedlinePlus related topics: Cystic Fibrosis

Drug Information available for: Tiotropium bromide

Genetic and Rare Diseases Information Center resources: Cystic Fibrosis

U.S. FDA Resources

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:

Percent Predicted FEV1 AUC0-4 Response at the End of Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
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.
Percent Predicted FEV1 Trough Response at the End of Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
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:

Percent Predicted FVC AUC0-4 Response at the End of Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
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.
Percent Predicted FVC Trough Response at the End of Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
Change from baseline in percent predicted trough Forced Vital Capacity (FVC). Calculated as percent predicted at week 12 minus percent predicted at baseline.
Pre-bronchodilator FEF25-75 Percent Predicted at the End of Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
Forced Expiratory Flow at 25-75% of vital capacity (FEF25-75). Calculated as percent predicted at week 12 minus percent predicted at baseline.
Change From Baseline in Residual Volume/Total Lung Capacity (RV/TLC) at the End of Week 12 [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
Change from baseline in static lung hyperinflation as measured by RV/TLC. Calculated as percent predicted at week 12 minus percent predicted at baseline.
Respiratory and Systemic Symptoms Questionnaire (RSSQ) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
Outcome measure description: The RSSQ questionnaire is used to determine the presence or absence of an exacerbation during the recall period.
Change From Baseline in CFQ Scores - Adult Group [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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.
Change From Baseline in CFQ Scores - Adolescents Group [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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.
Change From Baseline in CFQ Scores - Parent Questionnaire [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
Ae0-4,ss represents the amount of tiotropium that is eliminated in urine from time 0 to 4 hours at steady state
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 ] [ Designated as safety issue: No ]
Cmax,ss represents the maximum measured concentration of tiotropium in plasma at steady state.
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 ] [ Designated as safety issue: No ]
Tmax,ss represents the time from dosing to the maximum concentration of tiotropium in plasma
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) ] [ Designated as safety issue: No ]
Clinical Relevant Abnormalities for Vital Signs and Laboratory evaluation. Any new or clinically relevant worsening of baseline conditions was reported as Adverse Event.


Enrollment:	510
Study Start Date:	September 2008
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility


Ages Eligible for Study:	Child, Adult, Senior
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00737100

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Sponsors and Collaborators

Boehringer Ingelheim

Investigators


Study Chair:	Boehringer Ingelheim	Boehringer Ingelheim

More Information

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
Study First Received:	August 15, 2008
Results First Received:	March 21, 2011
Last Updated:	May 7, 2014
Health Authority:	Australia: Dept of Health and Ageing Therapeutic Goods Admin Belgium: Federal Agency for Medicines and Health Products, FAMHP France: French Health Products Safety Agency 143-147 boulevard Anatole France 93285 Saint-Denis Cedex FRANCE Germany: Federal Institute for Drugs and Medical Devices Great Britain: MHRA Italy: Ethics Committee Netherlands: Central Committee on Research involving human subjects (CCMO) New Zealand: Multicentre Ethics Committee/Medsafe Portugal: National Pharmacy and Medicines Institute Russia: Pharmacological Committee, Ministry of Health United States: Food and Drug Administration

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 Bromides Tiotropium Bromide Anticonvulsants	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

ClinicalTrials.gov processed this record on September 23, 2016