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

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)

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: tiotropium; Drug: tiotropium; Drug: olodaterol

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Komaki, Japan, 485-0041
    • Hiramatsu Internal and Respiratory Medicine Clinic
  • Aichi, Obu, Japan, 474-8511
    • National Hospital for Geriatric Medicine
  • Aichi, Seto, Japan, 489-8642
    • Tosei General Hospital
  • Fukuoka, Fukuoka, Japan, 819-8555
    • Nishi Fukuoka Hospital
  • Fukuoka, Kitakyushu, Japan, 802-0052
    • Kirigaoka Tsuda Hospital
  • Fukuoka, Kitakyushu, Japan, 802-0083
    • Osaki Internal and Respiratory Clinic
  • Fukuoka, Kurume, Japan, 830-0011
    • Kurume University Hospital
  • Gifu, Mizunami, Japan, 509-6134
    • Tohno Chuo Clinic
  • Hiroshima, Aki-gun, Japan, 735-8585
    • Mazda Hospital
  • Hokkaido, Sapporo, Japan, 060-8648
    • Hokkaido University Hospital
  • Hokkaido, Sapporo, Japan, 062-8618
    • Japan Community Health care Organization Hokkaido Hospital
  • Hokkaido, Sapporo, Japan, 006-0811
    • Teine Keijinkai Clinic
  • Hokkaido, Sapporo, Japan, 062-0931
    • KKR Sapporo Medical Center
  • Hyogo, Kobe, Japan, 650-0047
    • Kobe City Medical Center General Hospital
  • Hyogo, Kobe, Japan, 653-0013
    • Kobe City Hospital Organization Kobe City Medical Center West Hospital
  • Ibaraki, Naka-gun, Japan, 319-1113
    • Ibarakihigashi National Hospial
  • Iwate, Morioka, Japan, 020-8505
    • Iwate Medical University Hospital
  • Kagawa, Sakaide, Japan, 762-8550
    • Sakaide City Hospital
  • Kagoshima, Kagoshima, Japan, 890-8520
    • Kagoshima University Medical and Dental Hospital
  • Kanagawa, Kawasaki, Japan, 210-0852
    • Kokan Clinic
  • Kanagawa, Kawasaki, Japan, 215-0026
    • Shin-yurigaoka General Hospital
  • Kanagawa, Yokohama, Japan, 227-8501
    • Showa University Fujigaoka Hospital
  • Kyoto, Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Kyoto, Kyoto, Japan, 607-8062
    • Rakuwakai Otowa Hospital
  • Kyoto, Uji, Japan, 611-0041
    • Uji-Tokushukai Medical Center
  • Mie, Matsusaka, Japan, 515-8544
    • Matsusaka City Hospital
  • Miyagi, Sendai, Japan, 980-8574
    • Tohoku University Hospital
  • Miyagi, Sendai, Japan, 981-8563
    • Tohoku Rosai Hospital
  • Osaka, Kishiwada, Japan, 596-8501
    • Kishiwada City Hospital
  • Osaka, Osaka, Japan, 545-8586
    • Osaka City University Hospital
  • Osaka, Osakasayama, Japan, 589-8511
    • Kindai University Hospital
  • Osaka, Toyonaka, Japan, 560-8552
    • National Hospital Organization Toneyama National Hospital
  • Osaka, Yao, Japan, 581-0011
    • Yao Tokushukai General Hospital
  • Shimane, Izumo, Japan, 693-8501
    • Shimane University Hospital
  • Shizuoka, Hamamatsu, Japan, 434-8511
    • Tenryu Hospital
  • Tokyo, Bunkyo-ku, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Chiyoda-ku, Japan, 102-0074
    • The Respiratory Care Clinic, Nippon Medical School
  • Tokyo, Chuo-ku, Japan, 103-0025
    • Nihonbashi Sakura Clinic
  • Tokyo, Hachioji, Japan, 193-0998
    • Tokyo Medical University Hachioji Medical Center
  • Tokyo, Itabashi-ku, Japan, 173-8610
    • Nihon University Itabashi Hospital
  • Tokyo, Shinagawa-ku, Japan, 142-8666
    • Showa University Hospital
  • Tokyo, Shinjuku-ku, Japan, 169-0073
    • Shinjuku Research Park Clinic
  • Wakayama, Hidaka-gun, Japan, 644-0044
    • Wakayama National Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tiotropium + olodaterol; inhalation two puffs from the RESPIMAT inhaler, once a day, in the morning	Drug: tiotropium; Drug: tiotropium; fixed dose combination; Drug: olodaterol; fixed dose combination
Active Comparator: tiotropium; inhalation two puffs from the RESPIMAT inhaler, once a day, in the morning	Drug: tiotropium; Drug: tiotropium; fixed dose combination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inspiratory Capacity at Rest Measured at 60 Minutes Post-dose	At day 43 inspiratory capacity at rest measured at 60 minutes post-dose, after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	Day 43, 60 minutes post-dose after 6 weeks of each treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6-minute Walk Distance [Meter]	6-minute walk distance [Meter] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	Day 43, 60 minutes post-dose after 6 weeks of each treatment
Average Number of Step Per Day (Step/Day)	At day 43 adjusted mean (SE) of average number of step per day [step/day] treatment comparisons in measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	2 weeks prior to Week 6 per treatment
Average Daily Duration (Minutes) of ≥ 4 Metabolic Equivalents (METs)	At day 43 adjusted mean (SE) of average daily duration [minute] of ≥ 4 METs treatment comparisons measured by the activity monitor in the 2 weeks prior to week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	2 weeks prior to Week 6 per treatment
Average Daily Duration (Minutes) of ≥ 3 Metabolic Equivalents (METs)	At day 43 adjusted mean (SE) of average daily duration [minute] of ≥ 3 METs treatment comparisons measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	2 weeks prior to Week 6 per treatment
Average Daily Duration (Minutes) of ≥ 2 Metabolic Equivalents (METs)	At day 43 adjusted mean (SE) of average daily duration [minute] of ≥ 2 METs treatment comparison measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	2 weeks prior to Week 6 per treatment
Average Daily Active Strength (Metabolic Equivalents*Minutes) of ≥ 3 METs	At day 43 adjusted mean (SE) of average daily active strength [METs x minute] of >=3 METs treatment comparisons measured by the activity monitor in 2 weeks prior to Week 6 of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	2 weeks prior to Week 6 per treatment
60 Minutes Post-dose Slow Vital Capacity (SVC) (in Litre)	At day 43 adjusted mean (SE) of 60 minute post-dose slow vital capacity [Litre] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	Day 43, 60 minutes post-dose after 6 weeks of each treatment
30 Minutes Post-dose Forced Expiratory Volume in One Second (FEV1) (in Litre)	At day 43 adjusted mean (SE) of 30 minute post-dose forced expiratory volume in one second (FEV1) [Litre] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	Day 43, 30 minutes post-dose after 6 weeks of each treatment
30 Minutes Post-dose Forced Vital Capacity (FVC) (in Litre)	At day 43 adjusted mean (SE) of 30 minute post-dose forced vital capacity (FVC) [Litre] treatment comparisons after 6 weeks of each treatment. Adjusted mean was entered instead of mean in statistical analysis.	Day 43, 30 minutes post-dose after 6 weeks of each treatment

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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. Erratum In: Int J Chron Obstruct Pulmon Dis. 2019 Sep 03;14:2061-2064.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2016
• Primary Completion (Actual): March 24, 2017
• Study Completion (Actual): April 17, 2017

Study Registration Dates

• First Submitted: December 1, 2015
• First Submitted That Met QC Criteria: December 10, 2015
• First Posted (Estimate): December 15, 2015

Study Record Updates

• Last Update Posted (Actual): June 6, 2019
• Last Update Submitted That Met QC Criteria: March 1, 2019
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Olodaterol
• Other Study ID Numbers: 1237.33