Clinical trial NCT01762800: Evaluating the Control of COPD Symptoms in Patients Treated With Tiotropium Bromide 18mcg Once Daily Alone, ADOAIR 50/250mcg Twice Daily Alone or ADOAIR 50/250mcg Plus Tiotropium Bromide 18mcg
Official title: Evaluating the Control of COPD Symptoms in Patients Treated With Tiotropium Bromide 18mcg Once Daily Alone, ADOAIR 50/250mcg Twice Daily Alone or ADOAIR 50/250mcg Plus Tiotropium Bromide 18mcg
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-01-08
Enrollment: 407
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the control of COPD using a symptom and exacerbation risk based treatment strategy based on GOLD 2011. This study is conducted in Japanese subjects with COPD and assess whether the GOLD 2011 strategy is effective in medical practice in Japan.

Detailed description: PROTOCOL SUMMARY Rationale Both ADOAIR and tiotropium bromide ( hereinafter tiotropium）are now well established, effective treatments for COPD and are frequently co-prescribed (hereinafter TRIPLE therapy). The addition of ADOAIR to tiotropium improves lung function and quality of life and may further reduce exacerbations. GOLD 2011 thus recommends TRIPLE therapy as the second choice of COPD treatment strategy. However, the criteria for switching from each individual treatment to TRIPLE therapy are not clearly shown so far.

This study will be conducted in Japanese subjects with COPD and will assess whether the GOLD 2011 strategy is effective in medical practice in Japan.

Objective(s) The objective of the study is to assess the control of COPD using a symptom and exacerbation risk based treatment strategy based on GOLD 2011.

Study Design Multicenter, randomized, double-dummy, 24-weeks, observational study Study Endpoints/Assessments Primary

* Proportion of patients who were able to remain on the randomized therapy Secondary
* Proportion of patients who switched to TRIPLE therapy
* Proportion of patients who controlled by TRIPLE therapy
* Proportion of patients controlled by randomized therapy plus TRIPLE therapy
* Time to switching to TRIPLE therapy
* Time to first exacerbation
* Proportion of diagnosed exacerbation confirmed by Daily Record Card
* Proportion of exacerbations detected by Daily Record Card not diagnosed
* CAT score change
* Change in FEV1
* Use of relief medication
* Proportion of patients who decreased treatment from TRIPLE therapy
* Proportion of patients who required additional treatment to TRIPLE therapy
* Proportion of patients who dropped out
* Patients' judgment of treatment efficacy
* Physician's judgment of treatment efficacy

Safety

* Adverse event reporting
* Exacerbations of COPD

Eligibility criteria: Inclusion Criteria:

1. Male or female aged 40 - 80 years inclusive
2. Has an established clinical history of COPD (defined as per the GOLD definition)
3. The subject achieves a grade of ≥1 on mMRC at Visit 1
4. A signed and dated written informed consent is obtained from the subject prior to study participation
5. The subject has a post-bronchodilator FEV1 of ≥ 30% to ≤ 80% of predicted normal
6. The subject has a post-bronchodilator FEV1 / FVC ratio \< 70%
7. The subject is a current or ex-smoker with a smoking history of \> 10 pack-years Ex-smokers are required to have stopped smoking for at least 6 months prior to visit 1. Ex-smokers who stopped smoking less than 6 months ago will be defined as current smokers.
8. QTc \< 450 msec at Visit 1; or for patients with bundle branch block QTc should be \< 480 msec.

(QTc(F) \< 450 msec, or \< 480 msec in subjects with right bundle branch block, should be confirmed by the mean of three readings or one reading) 9. ALT \< 2 x ULN and bilirubin/ALP ≤ 1.5 x ULN (\> 35% direct bilirubin) 10. A female is eligible to enter this study if she is: i) of non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is post-menopausal), or ii) of child-bearing potential, but has a negative urinary pregnancy test at screening and agrees to take contraceptive precautions (including abstinence) which are adequate to prevent pregnancy during the study iii) not a nursing mother

Exclusion Criteria:

1. Has a predominant asthma (comorbid asthma is not an exclusion criteria)
2. Has a medical diagnosis of narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction that in the opinion of the investigator should prevent them from entering the study Note: As with other anticholinergic drugs, subjects with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction should only be entered into the study at the Investigator's discretion
3. Has known respiratory disorders other than COPD (e.g. lung cancer, sarcoidosis, tuberculosis or lung fibrosis)
4. Has undergone lung surgery e.g., lung transplant and/or lung volume reduction
5. Had a chest X-ray indicating diagnosis other than COPD that might interfere with the study (chest X-ray to be taken at Visit 1, if subject has not had one and/or CT image taken within 3 months of Visit 1)
6. Requires regular (daily) or long term oxygen therapy (LTOT). (LTOT is defined as ≥ 12 hours oxygen use per day)
7. Has plan to start or to change the pulmonary rehabilitation program during the study period
8. Requires regular treatment with oral, parenteral, or depot corticosteroids
9. Has serious, uncontrolled disease likely to interfere with the study (e.g. Left Ventricular failure, anaemia, renal or hepatic disease or serious psychological disorders)
10. Received any other investigational drugs within 4 weeks (or 5 half lives) prior to Visit 1
11. Has, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse
12. Has a known or suspected hypersensitivity to β2-agonists, steroids, anticholinergic treatments or any components of the formulations
13. Has previously been enrolled to this study and investigational drugs has been administered
14. Is not eligible to participate this study in the opinion of the investigator/subinvestigator

The investigator must refer to the following document(s) for detailed information regarding warnings, precautions, contraindications, adverse events, and other significant data pertaining to the investigational product(s) being used in this study:

1. ADOAIR DISKUS package insert
2. Tiotropium/ HandiHaler package insert
3. Salbutamol package insert

Primary outcomes:
measure: Percentage of Participants Who Were Able to Remain on the Randomized Treatment
timeFrame: 24 weeks
Secondary outcomes:
measure: Percentage of Participants Who Switched to TRIPLE Therapy
timeFrame: 24 weeks
measure: Percentage of Participants Managed by TRIPLE Therapy
timeFrame: 24 weeks
measure: Continuation Percentage of Participants Managed by Randomized Treatment Plus TRIPLE Therapy
timeFrame: 24 weeks
measure: Time to First Switching to TRIPLE Therapy
timeFrame: 24 weeks
measure: Time to First Exacerbation by Physician's Diagnosis
timeFrame: 24 weeks
measure: Time to First Exacerbation by EXAcerbations of Chronic Pulmonary Disease Tool (EXACT)
timeFrame: 24 weeks
measure: EXACT Total Score.
timeFrame: Baseline and up to 24 weeks
measure: EXACT Respiratory Symptoms (E-RS) Total Score
timeFrame: Baseline and up to 24 weeks
measure: E-RS Subscale Score
timeFrame: 24 weeks
measure: Comparison of Number of Exacerbations Between Two Detection Methods: EXACT and Physician Diagnosis
timeFrame: 24 weeks
measure: Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Total Score
timeFrame: 24 weeks
measure: Change From Baseline in CAT Total Score
timeFrame: Baseline and up to 24 weeks
measure: Forced Expiratory Volume in One Second (FEV1)
timeFrame: Up to 24 weeks
measure: Change From Baseline in FEV1
timeFrame: Baseline (Visit 2) and up to 24 weeks
measure: Percentage of Participants Who Used Relief Medication (Salbutamol)
timeFrame: 24 weeks
measure: Percentage of Participants Who Stepped Down From TRIPLE Therapy to Initial Randomized Treatment
timeFrame: 24 weeks
measure: Percentage of Participants Who Required Additional Treatment to TRIPLE Therapy
timeFrame: 24 weeks
measure: Percentage of Participants Who Dropped Out
timeFrame: 24 weeks
measure: Number of Participants in Each Treatment Efficacy Grade Evaluated by Participants
timeFrame: Up to 24 weeks
measure: Number of Participants in Each Treatment Efficacy Grade Evaluated by Physician
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kochi
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Nara
country: Japan
facility: GSK Investigational Site
city: Niigata
country: Japan
facility: GSK Investigational Site
city: Niigata
country: Japan
facility: GSK Investigational Site
city: Niigata
country: Japan
facility: GSK Investigational Site
city: Okinawa
country: Japan
facility: GSK Investigational Site
city: Okinawa
country: Japan
facility: GSK Investigational Site
city: Okinawa
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saga
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Yamaguchi
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Betsuyaku T, Kato M, Fujimoto K, Hagan G, Kobayashi A, Hitosugi H, James M, Jones PW. A study to assess COPD Symptom-based Management and to Optimise treatment Strategy in Japan (COSMOS-J) based on GOLD 2011. Int J Chron Obstruct Pulmon Dis. 2013;8:453-9. doi: 10.2147/COPD.S48298. Epub 2013 Oct 3.