Clinical trial NCT00824382: Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Japanese Patients With COPD
Official title: Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL Delivered by the Respimat Inhaler in Japanese 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: 2009-01-16
Enrollment: 328
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 inhalation solution delivered by the Respimat inhaler once daily for 4 weeks in Japanese patients with chronic obstructive pulmonary disease (COPD). The selection of the optimum dose(s) will be based on bronchodilator efficacy, safety evaluations and pharmacokinetic evaluations.


Eligibility criteria: Inclusion Criteria:

1. All patients must sign an informed consent consistent with GCP guidelines prior to participation in the trial.
2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria: Patients must have relatively stable, moderate to severe airway obstruction with a post-bronchodilator FEV1 \>=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. Pack-Years = \[Number of cigarettes/day/20\] - years of smoking Patients who have never smoked cigarettes must be excluded.
5. Patients must be able to perform technically acceptable pulmonary function tests (both supervised and unsupervised) and PEFR measurements, and must be able to record a patient 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 MDI.

Exclusion Criteria:

1. Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may i) put the patient at risk because of participation in the study ii) influence the results of the study, or iii) cause concern regarding the patient's ability to participate in the study
2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an AST \>80 IU/L, ALT \>80 IU/L, bilirubin \>1.5 x ULN or creatinine \>1.5 x ULN will be excluded regardless of clinical condition (a repeat laboratory evaluation will not be conducted in these patients)
3. Patients with a history of asthma or a total blood eosinophil count \>=600/mm3. A repeat eosinophil count will not be conducted in these patients
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 QTc interval \>450 ms) as recommended by ICH E14. For patients who have a QTc interval between 450 ms and 500 ms, as judged by site personnel, there will be a confirmatory reading by centralized evaluation institute. If the confirmatory reading is still greater than 450 ms, patient will be excluded. Patients with a QTc interval \>=500 ms will immediately be excluded from the study.
   * a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT Syndrome) as recommended by ICH E14.
5. Patients with any of the following conditions:

   * a history of myocardial infarction within 1 year
   * a diagnosis of clinically relevant cardiac arrhythmia
   * known active tuberculosis
   * a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last 5 years (patients with treated basal cell carcinoma are allowed)
   * 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 (patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1)
7. Patients being treated with any of the following concomitant medications:

   * medications that prolong the QT/QTc interval
   * oral beta-adrenergics and beta-adrenergics patchs
   * beta-blockers (topical beta-blockers for ocular conditions are allowed)
   * oral corticosteroid medication at unstable doses (i.e. less than 6 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.
8. Patients who regularly use daytime oxygen therapy for more than 1 hour per day and in the investigator's opinion will be unable to abstain from the use of oxygen therapy during clinic visits
9. Patients who have completed a pulmonary rehabilitation program in the 6 weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program
10. Patients who have taken an investigational drug within 1 month or 6 half lives (whichever is greater) prior to screening visit
11. Patients with known hypersensitivity to beta-adrenergics drugs, BAC, EDTA or any other component of the Respimat inhalation solution delivery system
12. Pregnant or suspect of pregnant or women who are willing to become pregnant during the study period or nursing women
13. Patients who have previously been participated in this study or are currently participating in another study
14. Patients who are unable to comply with pulmonary medication restrictions prior to randomisation
15. The randomization of patients with any respiratory infection or COPD exacerbation in the 6 weeks prior to the screening visit or during the screening period should be postponed. Patients may be randomised 6 weeks following recovery from the infection or exacerbation

Primary outcomes:
measure: Trough FEV1 Response at Week 4
timeFrame: baseline and after 4 weeks treatment
Secondary outcomes:
measure: Trough FEV1 Response at Week 2
timeFrame: baseline and after 2 weeks treatment
measure: FEV1 AUC(0-3) Response at 4 Weeks
timeFrame: baseline and after 4 weeks treatment
measure: FEV1 Peak(0-3) Response at 4 Weeks
timeFrame: baseline and after 4 weeks treatment
measure: Trough FVC Response at Week 4
timeFrame: baseline and after 4 weeks treatment
measure: FVC AUC(0-3) Response
timeFrame: baseline and after 4 weeks treatment
measure: FVC Peak(0-3) Response
timeFrame: baseline and after 4 weeks treatment
measure: Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 0-6h (AUC 0-6h) Response After 4 Weeks
timeFrame: baseline and after 4weeks treatment
measure: Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks
timeFrame: Baseline and after 4weeks treatment
measure: Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks
timeFrame: Week 4
measure: Weekly Mean Evening PEFR After 4 Weeks
timeFrame: Week 4
measure: Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks
timeFrame: Week 4
measure: Clinical Relevant Abnormalities for Vital Signs, Blood Chemistry, Haematology, Urinalysis, ECG and Physical Examination
timeFrame: 4 weeks
measure: Difference From Baseline in Potassium
timeFrame: Baseline, Week 4
measure: Cmax (Maximum Measured Concentration of the Analyte in Plasma)
timeFrame: after first inhalated administration
measure: Cmax,ss (Maximum Measured Concentration of the Analyte in Plasma at Steady State)
timeFrame: visit at week 4
measure: AUC0-1
timeFrame: after first inhalated administration
measure: AUC0-1,ss
timeFrame: visit at week 4
Other outcomes:
Locations:
city: Asahikawa, Hokkaido
country: Japan
facility: 1222.22.048 Boehringer Ingelheim Investigational Site
city: Bunkyo-ku, Tokyo
country: Japan
facility: 1222.22.044 Boehringer Ingelheim Investigational Site
city: Chiba, Chiba
country: Japan
facility: 1222.22.008 Boehringer Ingelheim Investigational Site
city: Fukuoka, Fukuoka
country: Japan
facility: 1222.22.002 Boehringer Ingelheim Investigational Site
city: Fukuoka, Fukuoka
country: Japan
facility: 1222.22.041 Boehringer Ingelheim Investigational Site
city: Himeji, Hyogo
country: Japan
facility: 1222.22.027 Boehringer Ingelheim Investigational Site
city: Himeji, Hyogo
country: Japan
facility: 1222.22.028 Boehringer Ingelheim Investigational Site
city: Hiroshima, Hiroshima
country: Japan
facility: 1222.22.018 Boehringer Ingelheim Investigational Site
city: Hitachi, Ibaraki
country: Japan
facility: 1222.22.021 Boehringer Ingelheim Investigational Site
city: Inashiki-gun, Ibaraki
country: Japan
facility: 1222.22.010 Boehringer Ingelheim Investigational Site
city: Itabashi-ku, Tokyo
country: Japan
facility: 1222.22.012 Boehringer Ingelheim Investigational Site
city: Kamogawa, Chiba
country: Japan
facility: 1222.22.009 Boehringer Ingelheim Investigational Site
city: Kawasaki, Kanagawa
country: Japan
facility: 1222.22.023 Boehringer Ingelheim Investigational Site
city: Kawasaki, Kanagawa
country: Japan
facility: 1222.22.025 Boehringer Ingelheim Investigational Site
city: Kishiwada, Osaka
country: Japan
facility: 1222.22.017 Boehringer Ingelheim Investigational Site
city: Kitakyusyu, Fukuoka
country: Japan
facility: 1222.22.004 Boehringer Ingelheim Investigational Site
city: Koga, Fukuoka
country: Japan
facility: 1222.22.020 Boehringer Ingelheim Investigational Site
city: Komaki, Aichi
country: Japan
facility: 1222.22.014 Boehringer Ingelheim Investigational Site
city: Kumamoto, Kumamoto
country: Japan
facility: 1222.22.032 Boehringer Ingelheim Investigational Site
city: Kurume, Fukuoka
country: Japan
facility: 1222.22.005 Boehringer Ingelheim Investigational Site
city: Kurume, Fukuoka
country: Japan
facility: 1222.22.029 Boehringer Ingelheim Investigational Site
city: Kyoto, Kyoto
country: Japan
facility: 1222.22.033 Boehringer Ingelheim Investigational Site
city: Kyoto, Kyoto
country: Japan
facility: 1222.22.050 Boehringer Ingelheim Investigational Site
city: Matsumoto, Nagano
country: Japan
facility: 1222.22.022 Boehringer Ingelheim Investigational Site
city: Nagoya, Aichi
country: Japan
facility: 1222.22.015 Boehringer Ingelheim Investigational Site
city: Nagoya, Aichi
country: Japan
facility: 1222.22.043 Boehringer Ingelheim Investigational Site
city: Naka-gun, Ibaraki
country: Japan
facility: 1222.22.001 Boehringer Ingelheim Investigational Site
city: Niigata, Niigata
country: Japan
facility: 1222.22.007 Boehringer Ingelheim Investigational Site
city: Obihiro, Hokkaido
country: Japan
facility: 1222.22.040 Boehringer Ingelheim Investigational Site
city: Okinawa, Okinawa
country: Japan
facility: 1222.22.042 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1222.22.034 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1222.22.038 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 1222.22.049 Boehringer Ingelheim Investigational Site
city: Osaka-sayama, Osaka
country: Japan
facility: 1222.22.045 Boehringer Ingelheim Investigational Site
city: Sakai, Oasaka
country: Japan
facility: 1222.22.019 Boehringer Ingelheim Investigational Site
city: Sapporo, Hokkaido
country: Japan
facility: 1222.22.006 Boehringer Ingelheim Investigational Site
city: Sashima-gun, Ibaraki
country: Japan
facility: 1222.22.051 Boehringer Ingelheim Investigational Site
city: Sendai, Miyagi
country: Japan
facility: 1222.22.031 Boehringer Ingelheim Investigational Site
city: Seto, Aichi
country: Japan
facility: 1222.22.013 Boehringer Ingelheim Investigational Site
city: Shibata-gun, Miyagi
country: Japan
facility: 1222.22.024 Boehringer Ingelheim Investigational Site
city: Takarazuka, Hyogo
country: Japan
facility: 1222.22.003 Boehringer Ingelheim Investigational Site
city: Tsukuba, Ibaraki
country: Japan
facility: 1222.22.026 Boehringer Ingelheim Investigational Site
city: Ube, Yamaguchi
country: Japan
facility: 1222.22.030 Boehringer Ingelheim Investigational Site
city: Uji, Kyoto
country: Japan
facility: 1222.22.037 Boehringer Ingelheim Investigational Site
city: Wakayama, Wakayama
country: Japan
facility: 1222.22.047 Boehringer Ingelheim Investigational Site
city: Yamagata, Yamagata
country: Japan
facility: 1222.22.016 Boehringer Ingelheim Investigational Site
city: Yao, Osaka
country: Japan
facility: 1222.22.036 Boehringer Ingelheim Investigational Site
city: Yokohama, Kanagawa
country: Japan
facility: 1222.22.011 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Ichinose M, Takizawa A, Izumoto T, Tadayasu Y, Hamilton AL, Kunz C, Fukuchi Y. Efficacy and safety of the long-acting beta2-agonist olodaterol over 4 weeks in Japanese patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2015 Aug 20;10:1673-83. doi: 10.2147/COPD.S86002. eCollection 2015.