Clinical trial NCT00696020: Combination of Orally Inhaled BI1744CL/Tiotropium Bromide in Patients With Chronic Obstructive Pulmonary Disease ( COPD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-06-12
Enrollment: 360
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility 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).

Further inclusion criteria apply

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

Further exclusion criteria apply

Primary outcomes:
measure: Trough FEV1 Response [L] After 4 Weeks of Treatment
timeFrame: Baseline and 4 weeks
Secondary outcomes:
measure: Trough FEV1 Response [L] After 1 and 2 Weeks of Treatment.
timeFrame: Baseline, 1 week and 2 weeks
measure: Trough FVC Response [L] After 1, 2 and 4 Weeks of Treatment
timeFrame: Baseline, 1 week, 2 weeks and 4 weeks
measure: FEV1 AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
timeFrame: 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
measure: FVC AUC(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment.
timeFrame: 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
measure: PEF AUC(0-3h) Response [L/Min] After First Administration and After 1, 2 and 4 Weeks of Treatment.
timeFrame: 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
measure: FEV1 AUC(0-6h) Response [L] After 4 Weeks of Treatment
timeFrame: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)
measure: FVC AUC(0-6h) Response [L] After 4 Weeks of Treatment
timeFrame: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)
measure: PEF AUC(0-6h) Response [L] After 4 Weeks of Treatment
timeFrame: 1 h and 10 min prior to inhalation at baseline and after 4 weeks and 30 min, 1 h, 2 h, 3 h, 4 h, 5 h and 6h after inhalation at baseline and after 4 weeks (Day 29)
measure: FEV1 Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
timeFrame: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
measure: FVC Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
timeFrame: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
measure: PEF Peak(0-3h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
timeFrame: 5 min (only for week 1 and 2), 30 min, 1 h, 2 h and 3 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
measure: FEV1 and PEF (Unsupervised) AUC(0-6h) Response [L] After First Administration and After 1, 2 and 4 Weeks of Treatment
timeFrame: After first administration, 1 week, 2 weeks and 4 weeks
measure: FEV1 (Unsupervised) AUC(6-12h) Response [L] After First Administration and 1,2 and 4 Weeks of Treatment
timeFrame: 6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
measure: PEF (Unsupervised) AUC(6-12h) Response [L/Min] After First Administration and 1,2 and 4 Weeks of Treatment
timeFrame: 6 h, 9 h and 12 h after inhalation at baseline and after 1 week, 2 weeks and 4 weeks
measure: Weekly Mean Pre-dose Morning PEF [L/Min]
timeFrame: Throughout the 4 week treatment period
measure: Weekly Mean Evening PEF [L/Min]
timeFrame: Throughout the 4 weeks treatment period
measure: Weekly Mean Number of Occasions of Rescue Therapy Used Per Day
timeFrame: Throughout the 4 weeks treatment period
measure: Physician's Global Evaluation
timeFrame: 1 week, 2 weeks and 4 weeks
measure: Patient's Global Rating
timeFrame: 4 weeks
measure: Clinically Significant Anormalities (Laboratory Data); Marked Changes From Baseline for Vital Signs, Notable Change in ECG and New Onset of ECG Abnormalities
timeFrame: From first dose up to 21 days after last dose of study medication.
measure: Cmax,ss Olodaterol [pg/mL]
timeFrame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
measure: Tmax,ss Olodaterol [h]
timeFrame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
measure: AUC(0-1h,ss) Olodaterol [pg*h/mL]
timeFrame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
measure: Cmax,ss Tiotropium [pg/mL]
timeFrame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
measure: Tmax,ss Tiotropium [h]
timeFrame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
measure: AUC(0-3h,ss) Tiotropium [pg*h/mL]
timeFrame: Pre-dose, 5 min, 10 min, 20 min, 40 min, 1 h, 3 h, and 6 h after the last dose.
Other outcomes:
Locations:
city: Riverside
country: United States
facility: 1237.4.0118 Boehringer Ingelheim Investigational Site
state: California
city: San Diego
country: United States
facility: 1237.4.0103 Boehringer Ingelheim Investigational Site
state: California
city: Wheat Ridge
country: United States
facility: 1237.4.0115 Boehringer Ingelheim Investigational Site
state: Colorado
city: Clearwater
country: United States
facility: 1237.4.0105 Boehringer Ingelheim Investigational Site
state: Florida
city: Deland
country: United States
facility: 1237.4.0110 Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: 1237.4.0117 Boehringer Ingelheim Investigational Site
state: Florida
city: Coeur d'Alene
country: United States
facility: 1237.4.0104 Boehringer Ingelheim Investigational Site
state: Idaho
city: Edina
country: United States
facility: 1237.4.0120 Boehringer Ingelheim Investigational Site
state: Minnesota
city: Minneapolis
country: United States
facility: 1237.4.0112 Boehringer Ingelheim Investigational Site
state: Minnesota
city: St. Charles
country: United States
facility: 1237.4.0119 Boehringer Ingelheim Investigational Site
state: Missouri
city: Raleigh
country: United States
facility: 1237.4.0114 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Philadelphia
country: United States
facility: 1237.4.0102 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: 1237.4.0111 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1237.4.0106 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1237.4.0107 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Knoxville
country: United States
facility: 1237.4.0123 Boehringer Ingelheim Investigational Site
state: Tennessee
city: Killeen
country: United States
facility: 1237.4.0122 Boehringer Ingelheim Investigational Site
state: Texas
city: New Braunfels
country: United States
facility: 1237.4.0109 Boehringer Ingelheim Investigational Site
state: Texas
city: Richmond
country: United States
facility: 1237.4.0108 Boehringer Ingelheim Investigational Site
state: Virginia
city: Spokane
country: United States
facility: 1237.4.0116 Boehringer Ingelheim Investigational Site
state: Washington
city: Tacoma
country: United States
facility: 1237.4.0121 Boehringer Ingelheim Investigational Site
state: Washington
city: Morgantown
country: United States
facility: 1237.4.0101 Boehringer Ingelheim Investigational Site
state: West Virginia
city: Winnipeg
country: Canada
facility: 1237.4.0203 Boehringer Ingelheim Investigational Site
state: Manitoba
city: Mississauga
country: Canada
facility: 1237.4.0201 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1237.4.0202 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1237.4.0205 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1237.4.0208 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sainte-Foy
country: Canada
facility: 1237.4.0206 Boehringer Ingelheim Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: 1237.4.0204 Boehringer Ingelheim Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: 1237.4.0207 Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Berlin
country: Germany
facility: 1237.4.4903 Boehringer Ingelheim Investigational Site
city: Erfurt
country: Germany
facility: 1237.4.4907 Boehringer Ingelheim Investigational Site
city: Gauting
country: Germany
facility: 1237.4.4902 Boehringer Ingelheim Investigational Site
city: Halle
country: Germany
facility: 1237.4.4908 Boehringer Ingelheim Investigational Site
city: Neuruppin
country: Germany
facility: 1237.4.4906 Boehringer Ingelheim Investigational Site
city: Rüdersdorf
country: Germany
facility: 1237.4.4904 Boehringer Ingelheim Investigational Site
city: Weinheim
country: Germany
facility: 1237.4.4901 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.