Clinical trial NCT01040403: Determining Optimal Free Dose Combination of Tiotropium Bromide and BI 1744 CL in Chronic Obstructive Pulmonary Disease (COPD)
Official title: A Randomised, Double-blind, 8 Treatments, 4 Periods, Incomplete Crossover Study to Determine the Optimal Free Dose Combination of BI 1744 CL and Tiotropium Bromide (Both Delivered by the Respimat® Inhaler) After 4 Weeks Once Daily Treatment 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: 2009-12-29
Enrollment: 233
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to determine the optimum once daily dose of BI 1744 CL and tiotropium in free dose combination (delivered by the Respimat inhaler) after four week treatment in patients with COPD.


Eligibility criteria: Inclusion criteria:

1. All patients must sign an informed consent
2. All patients must have a diagnosis of chronic obstructive pulmonary disease (COPD) must meet the following spirometric criteria:

a post-bronchodilator forced expiratory flow in 1 second (FEV1) =\<30% of predicted normal and \<80% of predicted normal and a post bronchodilator FEV1 / forced vital capacity (FVC) \<70% at Visit 1 4. Male or female patients, 40 years of age or older. 5. Patients must be current or ex-smokers with a smoking history of more than 10 pack years

Exclusion criteria:

* 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 (due to the known class side effect profile of ß2-agonists) a diagnosis of paroxysmal tachycardia - Patients with any of the following conditions: a history of myocardial infarction within 1 year of screening visit a diagnosis of clinically relevant cardiac arrhythmia a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years

* Patients who have undergone thoracotomy with pulmonary resection
* Patients being treated with the following concomitant medications:

medications that prolong the QT/QTc interval oral Beta-adrenergics oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day

- Pregnant or nursing women

Primary outcomes:
measure: Trough FEV1 Response
timeFrame: Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29
Secondary outcomes:
measure: Trough Forced Vital Capacity (FVC) Response
timeFrame: Baseline and 1 hour pre-dose and 10 minutes pre-dose on day 29
measure: FEV1 AUC 0-3h and FEV1 AUC 0-6h Response
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29
measure: FEV1 AUC 0-3h Response After the First Dose
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1
measure: FEV1 Peak 0-3h Response
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29
measure: FEV1 Peak 0-3h Response After the First Dose
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1
measure: FVC AUC 0-3h and FEV1 AUC 0-6h Responses
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29
measure: FVC AUC 0-3h Response After First Dose
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on days 1
measure: FVC Peak 0-3h Response
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29
measure: FVC Peak 0-3h Response After the First Dose
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1
measure: PEF AUC 0-3h and AUC 0-6h Responses
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post dose for AUC0-3h and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h 4 h, 5 h, 6 h postdose for AUC0-6h on day 29
measure: PEF AUC 0-3h Response After the First Dose
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1
measure: PEF Peak 0-3h Response
timeFrame: Baseline 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 29
measure: PEF Peak 0-3h Response After the First Dose
timeFrame: Baseline and 1 h, 10 min pre-dose and 5 min, 30 min, 1 h, 2 h, 3 h post-dose on day 1
measure: Individual FEV1 Measurements at Each Time Point on Day 29
timeFrame: Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29
measure: Individual FVC Measurements at Each Time Point on Day 29
timeFrame: Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29
measure: Individual PEF Measurements at Each Time Point on Day 29
timeFrame: Baseline and 1 h, 10 min pre-dose and 0 min, 5 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h post-dose on day 29
measure: Weekly Mean Number of Puffs of Rescue Medication Used Per Day
timeFrame: Weeks 1 and 4
measure: Physicians Global Evaluation
timeFrame: Days 1 and 29
measure: Patients Global Rating
timeFrame: Day 29
measure: Pulse Rate Recorded in Conjunction With Spirometry
timeFrame: Baseline and 30 min post-dose on day 29
measure: Systolic and Diastolic Blood Pressure Recorded in Conjunction With Spirometry
timeFrame: Baseline and 30 min post-dose on day 29
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: 1237.18.02004 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Grimsby
country: Canada
facility: 1237.18.02005 Boehringer Ingelheim Investigational Site
state: Ontario
city: Mississauga
country: Canada
facility: 1237.18.02001 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1237.18.02008 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1237.18.02002 Boehringer Ingelheim Investigational Site
state: Quebec
city: Point Claire
country: Canada
facility: 1237.18.02003 Boehringer Ingelheim Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: 1237.18.02007 Boehringer Ingelheim Investigational Site
state: Quebec
city: Saskatoon
country: Canada
facility: 1237.18.02011 Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Quebec
country: Canada
facility: 1237.18.02009 Boehringer Ingelheim Investigational Site
city: Aschaffenburg
country: Germany
facility: 1237.18.49009 Boehringer Ingelheim Investigational Site
city: Bamberg
country: Germany
facility: 1237.18.49012 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1237.18.49005 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1237.18.49004 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1237.18.49011 Boehringer Ingelheim Investigational Site
city: Koblenz
country: Germany
facility: 1237.18.49010 Boehringer Ingelheim Investigational Site
city: Mannheim
country: Germany
facility: 1237.18.49007 Boehringer Ingelheim Investigational Site
city: Potsdam
country: Germany
facility: 1237.18.49001 Boehringer Ingelheim Investigational Site
city: Rodgau-Dudenhofen
country: Germany
facility: 1237.18.49006 Boehringer Ingelheim Investigational Site
city: Rüdersdorf
country: Germany
facility: 1237.18.49002 Boehringer Ingelheim Investigational Site
city: Weinheim
country: Germany
facility: 1237.18.49003 Boehringer Ingelheim Investigational Site
city: Wiesloch
country: Germany
facility: 1237.18.49008 Boehringer Ingelheim Investigational Site
city: Almelo
country: Netherlands
facility: 1237.18.31004 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1237.18.31006 Boehringer Ingelheim Investigational Site
city: Eindhoven
country: Netherlands
facility: 1237.18.31008 Boehringer Ingelheim Investigational Site
city: Groningen
country: Netherlands
facility: 1237.18.31001 Boehringer Ingelheim Investigational Site
city: Hengelo
country: Netherlands
facility: 1237.18.31007 Boehringer Ingelheim Investigational Site
city: Hoorn
country: Netherlands
facility: 1237.18.31005 Boehringer Ingelheim Investigational Site
city: Veldhoven
country: Netherlands
facility: 1237.18.31002 Boehringer Ingelheim Investigational Site
city: Zutphen
country: Netherlands
facility: 1237.18.31003 Boehringer Ingelheim Investigational Site
city: Boden
country: Sweden
facility: 1237.18.46003 Boehringer Ingelheim Investigational Site
city: Göteborg
country: Sweden
facility: 1237.18.46002 Boehringer Ingelheim Investigational Site
city: Lund
country: Sweden
facility: 1237.18.46001 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 1237.18.46004 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Aalbers R, Maleki-Yazdi MR, Hamilton A, Waitere-Wijker S, Zhao Y, Amatto VC, Schmidt O, Bjermer L. Randomized, Double-Blind, Dose-Finding Study for Tiotropium when Added to Olodaterol, Administered via the Respimat(R) Inhaler in Patients with Chronic Obstructive Pulmonary Disease. Adv Ther. 2015 Sep;32(9):809-22. doi: 10.1007/s12325-015-0239-8. Epub 2015 Sep 24.