Combination of Orally Inhaled BI1744CL/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease ( COPD)

NCT00696020 | Completed Phase 2 Results

• 2 other identifiers: 1237.4EudraCT No: 2007-005087-26
• Study Type: interventional
• Target: 360
• Locations: 3 countries
• Sites: 37

Brief Summary

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

Conditions

Pulmonary Disease, Chronic Obstructive

Outcome Measures

Primary Outcomes (1)

• Trough FEV1 Response [L] After 4 Weeks of Treatment

  Trough FEV1 (Forced expiratory volume in 1 second) was defined as the mean of the two FEV1 values (performed at 1 h and 10 min prior to study medication inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response was defined as the change from baseline in trough FEV1. Baseline FEV1 was defined as the mean of the 2 pre-treatment FEV1 values measured at Visit 2 (-1 h and -10 min) prior to administration of the first dose of study medication. The means are adjusted, based on ANCOVA with terms for baseline, treatment, and centre (centre random, all other effects fixed).

  Baseline and 4 weeks

Secondary Outcomes (26)

• Trough FEV1 Response [L] After 1 and 2 Weeks of Treatment.

  Baseline, 1 week and 2 weeks

• Trough FVC Response [L] After 1, 2 and 4 Weeks of Treatment

  Baseline, 1 week, 2 weeks and 4 weeks

• FEV1 AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment

  1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks

• FVC AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment.

  1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks

• PEF AUC(0-3h) Response [L/Min] After First Administration and After 1, 2 and 4 Weeks of Treatment.

  1 h and 10 min prior to inhalation and 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1, 2 and 4 weeks

Study Arms (4)

BI 1744 CL low dose/tiotropium bromide

EXPERIMENTAL

BI 1744 CL low dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation

Drug: BI 1744 CL/tiotropium bromide fixed dose combination; Device: Respimat® Inhaler

BI1744CL medium dose/tiotropium bromide

EXPERIMENTAL

BI 1744 CL medium dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation

Drug: BI 1744 CL/tiotropium bromide fixed dose combination; Device: Respimat® Inhaler

BI 1744 CL high dose/tiotropium bromide

EXPERIMENTAL

BI 1744 CL high dose plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation

Drug: BI 1744 CL/tiotropium bromide fixed dose combination; Device: Respimat® Inhaler

tiotropium bromide

EXPERIMENTAL

tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation

Drug: tiotropium bromide; Device: Respimat® Inhaler

Interventions

BI 1744 CL/tiotropium bromide fixed dose combination DRUG

BI 1744 CL plus tiotropium bromide fixed dose combination; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation

BI 1744 CL high dose/tiotropium bromide; BI 1744 CL low dose/tiotropium bromide; BI1744CL medium dose/tiotropium bromide

tiotropium bromide DRUG

tiotropium bromide; Solution for inhalation via Respimat® Inhaler (A5); Oral inhalation

tiotropium bromide

Respimat® Inhaler DEVICE

BI 1744 CL high dose/tiotropium bromide; BI 1744 CL low dose/tiotropium bromide; BI1744CL medium dose/tiotropium bromide; tiotropium bromide

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients must sign an informed consent consistent with ICH-GCP guidelines prior to participation in the trial, which includes medication washout and restrictions
• 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
• Male or female patients, 40 years of age or older
• Patients must be current or ex-smokers with a smoking history of more than 10 pack years
• 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
• Patients must be able to inhale medication in a competent manner from the Respimat inhaler and from a metered dose inhaler (MDI).

You may not qualify if:

• Patients with a significant disease other than COPD
• Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis;
• Patients with a history of asthma or a total blood eosinophil count \>= 600/mm3.
• 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)
• 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
• Patients who have undergone thoracotomy with pulmonary resection
• 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.
• Pregnant or nursing women
• 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
• Patients who have previously been randomized in this study or are currently participating in another study
• Patients who are unable to comply with pulmonary medication restrictions prior to randomization
• Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (37)

1237.4.0118 Boehringer Ingelheim Investigational Site

Riverside, California, United States

Location

1237.4.0103 Boehringer Ingelheim Investigational Site

San Diego, California, United States

Location

1237.4.0115 Boehringer Ingelheim Investigational Site

Wheat Ridge, Colorado, United States

Location

1237.4.0105 Boehringer Ingelheim Investigational Site

Clearwater, Florida, United States

Location

1237.4.0110 Boehringer Ingelheim Investigational Site

DeLand, Florida, United States

Location

1237.4.0117 Boehringer Ingelheim Investigational Site

Tampa, Florida, United States

Location

1237.4.0104 Boehringer Ingelheim Investigational Site

Coeur d'Alene, Idaho, United States

Location

1237.4.0120 Boehringer Ingelheim Investigational Site

Edina, Minnesota, United States

Location

1237.4.0112 Boehringer Ingelheim Investigational Site

Minneapolis, Minnesota, United States

Location

1237.4.0119 Boehringer Ingelheim Investigational Site

Saint Charles, Missouri, United States

Location

1237.4.0114 Boehringer Ingelheim Investigational Site

Raleigh, North Carolina, United States

Location

1237.4.0102 Boehringer Ingelheim Investigational Site

Philadelphia, Pennsylvania, United States

Location

1237.4.0111 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

Location

1237.4.0106 Boehringer Ingelheim Investigational Site

Spartanburg, South Carolina, United States

Location

1237.4.0107 Boehringer Ingelheim Investigational Site

Spartanburg, South Carolina, United States

Location

1237.4.0123 Boehringer Ingelheim Investigational Site

Knoxville, Tennessee, United States

Location

1237.4.0122 Boehringer Ingelheim Investigational Site

Killeen, Texas, United States

Location

1237.4.0109 Boehringer Ingelheim Investigational Site

New Braunfels, Texas, United States

Location

1237.4.0108 Boehringer Ingelheim Investigational Site

Richmond, Virginia, United States

Location

1237.4.0116 Boehringer Ingelheim Investigational Site

Spokane, Washington, United States

Location

1237.4.0121 Boehringer Ingelheim Investigational Site

Tacoma, Washington, United States

Location

1237.4.0101 Boehringer Ingelheim Investigational Site

Morgantown, West Virginia, United States

Location

1237.4.0203 Boehringer Ingelheim Investigational Site

Winnipeg, Manitoba, Canada

Location

1237.4.0201 Boehringer Ingelheim Investigational Site

Mississauga, Ontario, Canada

Location

1237.4.0202 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1237.4.0205 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1237.4.0208 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1237.4.0206 Boehringer Ingelheim Investigational Site

Sainte-Foy, Quebec, Canada

Location

1237.4.0204 Boehringer Ingelheim Investigational Site

Sherbrooke, Quebec, Canada

Location

1237.4.0207 Boehringer Ingelheim Investigational Site

Saskatoon, Saskatchewan, Canada

Location

1237.4.4903 Boehringer Ingelheim Investigational Site

Berlin, Germany

Location

1237.4.4907 Boehringer Ingelheim Investigational Site

Erfurt, Germany

Location

1237.4.4902 Boehringer Ingelheim Investigational Site

Gauting, Germany

Location

1237.4.4908 Boehringer Ingelheim Investigational Site

Halle, Germany

Location

1237.4.4906 Boehringer Ingelheim Investigational Site

Neuruppin, Germany

Location

1237.4.4904 Boehringer Ingelheim Investigational Site

Rüdersdorf, Germany

Location

1237.4.4901 Boehringer Ingelheim Investigational Site

Weinheim, Germany

Location

Related Publications (1)

• Maltais F, Hamilton A, Voss F, Maleki-Yazdi MR. Dose Determination for a Fixed-Dose Drug Combination: A Phase II Randomized Controlled Trial for Tiotropium/Olodaterol Versus Tiotropium in Patients with COPD. Adv Ther. 2019 Apr;36(4):962-968. doi: 10.1007/s12325-019-00911-y. Epub 2019 Mar 6.

  PMID: 30843141 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Limitations and Caveats

Additional secondary endpoints were listed in the original protocol. Those endpoints are of exploratory nature only and were not considered relevant for trial conclusions. For more information see tab "Full Text Review", section "More Information".

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2008
• First Posted: June 12, 2008
• Study Start: June 1, 2008
• Primary Completion: February 1, 2009
• Last Updated: August 13, 2015
• Results First Posted: August 13, 2015

Record last verified: 2015-07

Locations

CA (8); DE (7); US (22)