Clinical trial NCT02629965: Comparing the Efficacy of Tiotropium + Olodaterol Fixed Dose Combination (FDC) Over Tiotropium in Improvement of Lung Hyperinflation, Exercise Capacity and Physical Activity in Japanese COPD Patients
Official title: A Randomised, Double-blinded, Active-controlled 2-way Cross Over Trial to Assess the Effects of 6 Weeks Treatment of Once Daily Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination Delivered by RESPIMAT Inhaler Compared With Tiotropium Delivered by RESPIMAT Inhaler on Lung Hyperinflation, Exercise Capacity and Physical Activity in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2015-12-15
Enrollment: 184
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: This is a multi-centre, randomised, double-blinded, active-controlled, 2-way cross over trial to assess the effects of once daily administration of orally inhaled tiotropium + olodaterol FDC or tiotropium (both delivered by the RESPIMAT Inhaler) on pulmonary function (lung hyperinflation), exercise capacity (6-minute walk distance) and physical activities after 6 weeks of treatment in Japanese patients with Chronic Obstructive Pulmonary Disease.


Eligibility criteria: Inclusion criteria:

* All patients must sign an informed consent consistent with International Conference on Harmonization - Good Clinical Practice (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 (COPD) and must meet the following spirometric criteria:

Patients must have relatively stable airway obstruction with a post-bronchodilator Forced expiratory volume in one second (FEV1) \< 80% of predicted normal and post-bronchodilator FEV1/forced vital capacity (FVC) \< 70% at Visit 1.

* Male or female patients, aged \>= 40 years.
* Patients must be current or ex-smokers with a smoking history of more than 10 pack years. Patients who have never smoked cigarettes must be excluded.
* Patients with score on the modified Medical Research Council (mMRC) \>= 1.
* Patients who walk \< 400 meters of 6MWT and have a score on the modified Borg \>= 4 at the end of 6 minute walk test (6MWT) at Visit 2.
* Patients must be able to perform technically acceptable pulmonary function tests (spirometry), to use the physical activity monitor and must be able to complete 6MWT 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.

Exclusion criteria:

* Patients with a significant disease other than COPD; a significant disease is defined as a disease which, in the opinion of the investigator, may put the patient at risk because of participation in the study, influence the results of the study and cause concern regarding the patient's ability to participate in the study.
* Patients with clinically relevant abnormal baseline haematology, blood chemistry,urinalysis or creatinine \> x2 upper limit of normal (ULN) will be excluded regardless of clinical condition (a repeat laboratory evaluation can be conducted if deemed necessary by the investigator).
* Patients with a current documented diagnosis of asthma. For patients with allergic rhinitis or atopy, source documentation is required to verify that the patient does not have asthma.
* Further exclusion criteria apply

Primary outcomes:
measure: Inspiratory Capacity at Rest Measured at 60 Minutes Post-dose
timeFrame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
Secondary outcomes:
measure: 6-minute Walk Distance [Meter]
timeFrame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
measure: Average Number of Step Per Day (Step/Day)
timeFrame: 2 weeks prior to Week 6 per treatment
measure: Average Daily Duration (Minutes) of ≥ 4 Metabolic Equivalents (METs)
timeFrame: 2 weeks prior to Week 6 per treatment
measure: Average Daily Duration (Minutes) of ≥ 3 Metabolic Equivalents (METs)
timeFrame: 2 weeks prior to Week 6 per treatment
measure: Average Daily Duration (Minutes) of ≥ 2 Metabolic Equivalents (METs)
timeFrame: 2 weeks prior to Week 6 per treatment
measure: Average Daily Active Strength (Metabolic Equivalents*Minutes) of ≥ 3 METs
timeFrame: 2 weeks prior to Week 6 per treatment
measure: 60 Minutes Post-dose Slow Vital Capacity (SVC) (in Litre)
timeFrame: Day 43, 60 minutes post-dose after 6 weeks of each treatment
measure: 30 Minutes Post-dose Forced Expiratory Volume in One Second (FEV1) (in Litre)
timeFrame: Day 43, 30 minutes post-dose after 6 weeks of each treatment
measure: 30 Minutes Post-dose Forced Vital Capacity (FVC) (in Litre)
timeFrame: Day 43, 30 minutes post-dose after 6 weeks of each treatment
Other outcomes:
Locations:
city: Aichi, Komaki
country: Japan
facility: Hiramatsu Internal and Respiratory Medicine Clinic
city: Aichi, Obu
country: Japan
facility: National Hospital for Geriatric Medicine
city: Aichi, Seto
country: Japan
facility: Tosei General Hospital
city: Fukuoka, Fukuoka
country: Japan
facility: Nishi Fukuoka Hospital
city: Fukuoka, Kitakyushu
country: Japan
facility: Kirigaoka Tsuda Hospital
city: Fukuoka, Kitakyushu
country: Japan
facility: Osaki Internal and Respiratory Clinic
city: Fukuoka, Kurume
country: Japan
facility: Kurume University Hospital
city: Gifu, Mizunami
country: Japan
facility: Tohno Chuo Clinic
city: Hiroshima, Aki-gun
country: Japan
facility: Mazda Hospital
city: Hokkaido, Sapporo
country: Japan
facility: Teine Keijinkai Clinic
city: Hokkaido, Sapporo
country: Japan
facility: Hokkaido University Hospital
city: Hokkaido, Sapporo
country: Japan
facility: KKR Sapporo Medical Center
city: Hokkaido, Sapporo
country: Japan
facility: Japan Community Health Care Organization Hokkaido Hospital
city: Hyogo, Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
city: Hyogo, Kobe
country: Japan
facility: Kobe City Hospital Organization Kobe City Medical Center West Hospital
city: Ibaraki, Naka-gun
country: Japan
facility: Ibarakihigashi National Hospial
city: Iwate, Morioka
country: Japan
facility: Iwate Medical University Hospital
city: Kagawa, Sakaide
country: Japan
facility: Sakaide City Hospital
city: Kagoshima, Kagoshima
country: Japan
facility: Kagoshima University Medical And Dental Hospital
city: Kanagawa, Kawasaki
country: Japan
facility: Kokan Clinic
city: Kanagawa, Kawasaki
country: Japan
facility: Shin-yurigaoka General Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Showa University Fujigaoka Hospital
city: Kyoto, Kyoto
country: Japan
facility: Kyoto University Hospital
city: Kyoto, Kyoto
country: Japan
facility: Rakuwakai Otowa Hospital
city: Kyoto, Uji
country: Japan
facility: Uji-Tokushukai Medical Center
city: Mie, Matsusaka
country: Japan
facility: Matsusaka City Hospital
city: Miyagi, Sendai
country: Japan
facility: Tohoku University Hospital
city: Miyagi, Sendai
country: Japan
facility: Tohoku Rosai Hospital
city: Osaka, Kishiwada
country: Japan
facility: Kishiwada City Hospital
city: Osaka, Osakasayama
country: Japan
facility: Kindai University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka City University Hospital
city: Osaka, Toyonaka
country: Japan
facility: National Hospital Organization Toneyama National Hospital
city: Osaka, Yao
country: Japan
facility: Yao Tokushukai General Hospital
city: Shimane, Izumo
country: Japan
facility: Shimane University Hospital
city: Shizuoka, Hamamatsu
country: Japan
facility: Tenryu Hospital
city: Tokyo, Bunkyo-ku
country: Japan
facility: Juntendo University Hospital
city: Tokyo, Chiyoda-ku
country: Japan
facility: The Respiratory Care Clinic, Nippon Medical School
city: Tokyo, Chuo-ku
country: Japan
facility: Nihonbashi Sakura Clinic
city: Tokyo, Hachioji
country: Japan
facility: Tokyo Medical University Hachioji Medical Center
city: Tokyo, Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
city: Tokyo, Shinagawa-ku
country: Japan
facility: Showa University Hospital
city: Tokyo, Shinjuku-ku
country: Japan
facility: Shinjuku Research Park Clinic
city: Wakayama, Hidaka-gun
country: Japan
facility: Wakayama National Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Minakata Y, Motegi T, Ueki J, Gon Y, Nakamura S, Anzai T, Hirata K, Ichinose M. Effect of tiotropium/olodaterol on sedentary and active time in patients with COPD: post hoc analysis of the VESUTO(R) study. Int J Chron Obstruct Pulmon Dis. 2019 Aug 7;14:1789-1801. doi: 10.2147/COPD.S208081. eCollection 2019.