Combination of Orally Inhaled BI1744Cl/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease ( COPD)

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00696020
First received: June 10, 2008
Last updated: March 28, 2014
Last verified: March 2014
  Purpose

The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL administered with 5 mic tiotropium bromide solution for inhalation, delivered by the Respimat inhaler, once daily for four weeks in patients with chronic obstructive pulmonary disease (COPD).


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: BI1744/Tiotropium bromide
Drug: Tiotropium bromide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: Randomised, Double-Blind, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of 3 Doses of Orally Inhaled BI 1744 CL, Each in Fixed Dose Combination With 5 Microgram Tiotropium Bromide (Delivered by the Respimat Inhaler) Compared With 5 Microgram Tiotropium Bromide Monoproduct (Delivered by the Respimat Inhaler) in Patients With COPD

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Trough FEV1 response [L] [ Time Frame: 4 weeks of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Trough FEV1 response [L] [ Time Frame: after 1 and 2 weeks of treatment ] [ Designated as safety issue: No ]
  • Trough FVC (forced vital capacity) response [L] [ Time Frame: after 1, 2 and 4 weeks of treatment ] [ Designated as safety issue: No ]
  • FEV1response [L] AUC0-3h [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • FVC response [L] AUC0-3h [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • PEF (supervised) AUC0-3h [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • FEV1response [L] AUC0-6h [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • FVC response [L] AUC0-6h [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • PEF (supervised) AUC0-6h [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • FEV1response [L] peak0-3h [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • FVC response [L] peak0-3h [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • PEF (supervised) peak0-3h [ Time Frame: after 4 weeks of treatment ] [ Designated as safety issue: No ]
  • FEV1response [L] peak0-3h [ Time Frame: after the first dose and after 1 and 2 weeks of treatment ] [ Designated as safety issue: Yes ]
  • FVC response [L] peak0-3h [ Time Frame: after the first dose and after 1 and 2 weeks of treatment ] [ Designated as safety issue: No ]
  • PEF (supervised) peak0-3h [ Time Frame: after the first dose and after 1 and 2 weeks of treatment ] [ Designated as safety issue: No ]
  • FEV1 response AUC0-6h [ Time Frame: 4 weeks of treatment ] [ Designated as safety issue: No ]
  • PEF response (unsupervised) AUC0-6h [ Time Frame: 4 weeks of treatment ] [ Designated as safety issue: No ]
  • FEV1 response AUC6-12h [ Time Frame: 4 weeks of treatment ] [ Designated as safety issue: No ]
  • PEF (unsupervised) response AUC6-12h [ Time Frame: 4 weeks of treatment ] [ Designated as safety issue: No ]
  • FEV1 response AUC0-6h [ Time Frame: after the first dose and after 1 and 2 weeks of treatment ] [ Designated as safety issue: No ]
  • PEF (unsupervised) response AUC0-6h [ Time Frame: after the first dose and after 1 and 2 weeks of treatment ] [ Designated as safety issue: No ]
  • FEV1 response AUC6-12h [ Time Frame: after the first dose and after 1 and 2 weeks of treatment ] [ Designated as safety issue: No ]
  • PEF (unsupervised) response AUC6-12h [ Time Frame: after the first dose and after 1 and 2 weeks of treatment ] [ Designated as safety issue: No ]
  • Weekly mean pre-dose morning and evening PEF (peak expiratory flow rate) [L/min] [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
  • Weekly mean number of occasions of rescue therapy used per day [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
  • Physician's Global Evaluation on a 8-point scale [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • Patient's Global Rating on a 7-point scale [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • Incidence of adverse events [ Time Frame: up to 8 weeks ] [ Designated as safety issue: No ]
  • Pulse rate and blood pressure (seated) recorded in conjunction with spirometry [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • 12-lead ECG abnormalities at baseline (-30 minutes) and at 10 minutes post-dose; plus 1 hour post-dose [ Time Frame: up to 8 weeks of treatment ] [ Designated as safety issue: No ]
  • Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state) [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose) [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • AUCt1-t2,ss (area under the concentration-time curve of the analyte in plasma at steady state over the time interval from t1 to t2) [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • CL/F,ss (apparent clearance of the analyte in the plasma at steady state following extravascular multiple dose administration) [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • Aet1-t2,ss (amount of analyte that is eliminated in urine at steady state from the time point t1 to t2 at steady state) [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • fet1-t2,ss (fraction of analyte eliminated in urine at steady state from time point t1 to t2 at steady state) [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]
  • CLR,t1-t2,ss (renal clearance of the analyte in plasma from the time point t1 to t2 at steady state) [ Time Frame: up to 4 weeks of treatment ] [ Designated as safety issue: No ]

Enrollment: 360
Study Start Date: June 2008
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions
  2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:

    Patients must have relatively stable airway obstruction with a post-bronchodilator FEV1 greater or equal 30% of predicted normal and <80% of predicted normal and a post-bronchodilator FEV1 / FVC <70% at Visit 1

  3. Male or female patients, 40 years of age or older
  4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years
  5. Patients must be able to perform technically acceptable pulmonary function tests and PEF measurements, and must be able to maintain records (Patient Daily e-Diary) during the study period as required in the protocol
  6. Patients must be able to inhale medication in a competent manner from the Respimat inhaler and from a metered dose inhaler (MDI).

Exclusion Criteria:

  1. Patients with a significant disease other than COPD
  2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
  3. Patients with a history of asthma or a total blood eosinophil count >= 600/mm3.
  4. Patients with any of the following conditions:a diagnosis of thyrotoxicosis, a diagnosis of paroxysmal tachycardia (>100 beats per minute), a marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTcF* interval > 450 ms), a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)
  5. Patients with any of the following conditions:a history of myocardial infarction within 1 year of screening visit (Visit 1), a diagnosis of clinically relevant cardiac arrhythmia, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years, a history of life-threatening pulmonary obstruction, a history of cystic fibrosis, clinically evident bronchiectasis, a history of significant alcohol or drug abuse
  6. Patients who have undergone thoracotomy with pulmonary resection
  7. Patients who regularly use daytime oxygen therapy for more than one hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits.
  8. Pregnant or nursing women
  9. Women of childbearing potential not using two effective method of birth control (one barrier and one non-barrier). Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years
  10. Patients who have previously been randomized in this study or are currently participating in another study
  11. Patients who are unable to comply with pulmonary medication restrictions prior to randomization
  12. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit
  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: NCT00696020

  Show 37 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00696020     History of Changes
Other Study ID Numbers: 1237.4, EudraCT No: 2007-005087-26
Study First Received: June 10, 2008
Last Updated: March 28, 2014
Health Authority: Canada: Health Canada (TPD)
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Tiotropium
Bromides
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014