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

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00737100
First received: August 15, 2008
Last updated: May 7, 2014
Last verified: January 2014
  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:


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

Genders Eligible for Study:   Both
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
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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United States, Arizona
205.339.006 Boehringer Ingelheim Investigational Site
Tucson, Arizona, United States
United States, California
205.339.019 Boehringer Ingelheim Investigational Site
San Diego, California, United States
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205.339.023 Boehringer Ingelheim Investigational Site
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205.339.110 Boehringer Ingelheim Investigational Site
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205.339.3310A Boehringer Ingelheim Investigational Site
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205.339.3317D Boehringer Ingelheim Investigational Site
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Lisieux, France
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Montpellier, France
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Rennes, France
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Wolverhampton, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

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:
Cystic Fibrosis
Fibrosis
Tiotropium
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Bromides
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
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 August 28, 2014