ADOAIR250 Anti-inflammatory Effects in Japanese Subjects With Chronic Obstructive Pulmonary Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01607398
First received: May 10, 2012
Last updated: April 24, 2014
Last verified: March 2014
  Purpose

The study will be conducted in a respiratory specialist institute in Japan, with standardized techniques and data assurance checks to optimize data quality. The licensed dosage and administration of Adoair in Japan will be applied in this study. Each subject will receive treatment options in a randomized blinded fashion. Subjects will be randomized following a 4-week wash-out phase to take either Adoair 50/250mcg twice daily or placebo twice daily for 12 weeks.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: ADOAIR250
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 12-week Randomised, Double-blind, Parallel-group Study to Evaluate the Anti-inflammatory Effects of ADOAIR® 50/250mcg Twice Daily Compared With Placebo Twice Daily in Japanese Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline in Neutrophil Count in Induced Sputum at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Induced sputum samples were collected at Baseline and at Week 12. The neutrophil count in induced sputum was measured with the use of a cytological specimen of inflammatory cells in the induced sputum. Change from Baseline in neutrophil count was calculated as the Week 12 value minus the Baseline value (percentage of neutrophil of total cells in induced sputum at Week 12 minus the Baseline value).


Secondary Outcome Measures:
  • Change From Baseline in All Inflammatory Cell Count in Induced Sputum at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Induced sputum samples were collected at Baseline and at Week 12. All inflammatory cells in induced sputum were counted with the use of a cytological specimen of cells in the induced sputum. Change from Baseline in all inflammatory cell count was calculated as the Week 12 value minus the Baseline value.

  • Change From Baseline in Interferon (INF)-Gamma-positive Cells and Perforin-positive Cells in Sputum at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    INF-gamma-positive cells and perforin-positive cells were not detected in samples collected in this study due to the conditions of the samples and/or antibodies. No re-assays were performed, "no result"/"no data" was entered into the case report forms, and no statistical analysis or data summarization was performed.

  • Change From Baseline in Interleukin (IL)-8 Levels in Sputum Supernatant at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Induced sputum samples were collected at Baseline and at Week 12. The levels of IL-8 in the supernatant of an induced sputum sample were measured at the same time using the multiplex assay system. Change from Baseline in IL-8 levels was calculated as the Week 12 value minus the Baseline value.

  • Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) Levels in Sputum Supernatant at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Data cannot be reported because hsCRP was under the lower limit of detection in all samples.

  • Change From Baseline in Myeloperoxidase (MPO) and Pulmonary Surfactant Protein (SP)-D Levels in Sputum Supernatant at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Induced sputum samples were collected at Baseline and at Week 12. The levels of MPO and SP-D in the supernatant of an induced sputum sample were measured at the same time using the multiplex assay system. Change from Baseline in MPO and SP-D levels was calculated as the Week 12 value minus the Baseline value.

  • Change From Baseline in IL-6 and IL-8 Levels in Serum at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Serum samples were collected at Baseline and at Week 12. The levels of IL-6 and IL-8 in serum samples were measured at the same time using the multiplex assay system. Change from Baseline in IL-6 and IL-8 levels was calculated as the Week 12 value minus the Baseline value.

  • Change From Baseline in hsCRP, SP-D, and Clara Cell Protein 16 (CC 16) Levels in Serum at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Serum samples were collected at Baseline and at Week 12. The levels of hsCRP, SP-D, and CC16 in serum samples were measured at the same time using the multiplex assay system. Change from Baseline in hsCRP, SP-D, and CC16 was calculated as the Week 12 value minus the Baseline value.

  • Change From Baseline in Fibrinogen Levels in Serum at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Per Protocol Amendment 4, the measurement of fibrinogen levels in serum was removed from the analysis plan because fibrinogen levels were found to be too low and too difficult to measure.

  • Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. Respiratory function tests were performed for the measurement of FEV1 and FVC at Baseline and at Week 12. The values were measured at 15 to 60 minutes following the use of a pressurized metered-dose inhaler. Three technically acceptable values were obtained, and the highest value was recorded. Change from Baseline in FEV1 and FVC was calculated as the Week 12 value minus the Baseline value.

  • Change From Baseline in the COPD Assessment Test (CAT) Question 1 Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 1, participants were asked to rate how much they cough on a scale of 0 to 5: 0, "I never cough"; 5, "I cough all the time." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

  • Change From Baseline in the COPD Assessment Test (CAT) Question 2 Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 2, participants were asked to rate the amount of phlegm (mucus) in their chest on a scale of 0 to 5: 0, "I have no phlegm (mucus) in my chest at all"; 5, "My chest is completely full of phlegm (mucus)." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

  • Change From Baseline in the COPD Assessment Test (CAT) Question 3 Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 3, participants were asked to rate how tight their chest feels on a scale of 0 to 5: 0, "My chest does not feel tight at all"; 5, "My chest feels very tight." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

  • Change From Baseline in the COPD Assessment Test (CAT) Question 4 Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 4, participants were asked to rate how breathless they feel when walking up a flight of stairs or a hill on a scale of 0 to 5: 0, "When I walk up a hill or one flight of stairs I am not breathless"; 5, "When I walk up a hill or one flight of stairs I am very breathless." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

  • Change From Baseline in the COPD Assessment Test (CAT) Question 5 Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 5, participants were asked to rate how limited they are in doing activities at home on a scale of 0 to 5: 0, "I am not limited doing any activities at home"; 5, "I am very limited doing activities at home." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

  • Change From Baseline in the COPD Assessment Test (CAT) Question 6 Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 6, participants were asked to rate how confident they are leaving home despite their lung condition on a scale of 0 to 5: 0, "I am confident leaving my home despite my lung condition"; 5, "I am not at all confident leaving my home because of my lung condition." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

  • Change From Baseline in the COPD Assessment Test (CAT) Question 7 Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 7, participants were asked to rate how soundly they sleep on a scale of 0 to 5: 0, "I sleep soundly"; 5, "I don't sleep soundly because of my lung condition." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

  • Change From Baseline in the COPD Assessment Test (CAT) Question 8 Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8) designed to assess the health status of participants with COPD. In Question 8, participants were asked to rate how much energy they have on a scale of 0 to 5: 0, "I have lots of energy"; 5, "I have no energy at all." Change from Baseline was calculated as the Week 12 score minus the Baseline score.

  • Change From Baseline in the COPD Assessment Test (CAT) Total Score at Week 12 [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    Participants completed the CAT questionnaire before undergoing respiratory function tests at Baseline and at Week 12. The CAT questionnaire is an 8-item questionnaire (comprised of Question [Q] 1 to Q8; each question scored from 0 to 5) designed to assess the health status of participants with COPD. The total score is calculated as the sum of the scores from Questions 1 to 8, for a range of possible scores of 0 to 40. A higher total score represents a lower quality of life, and vice versa. Change from Baseline was calculated as the Week 12 score minus the Baseline score.

  • Number of Participants Who Experienced the Indicated Number of COPD Exacerbations During the Treatment Period [ Time Frame: From Baseline up to Week 12 ] [ Designated as safety issue: No ]
    The occurrence of a COPD exacerbation was assessed on each day of evaluation during the treatment period per the defined severity classifications. COPD exacerbations were classified based on severity as a mild exacerbation (exacerbation of COPD symptoms were manageable by the participant, not requiring systemic corticosteroid or antimicrobial therapy), a moderate exacerbation (exacerbation of COPD symptoms required systemic corticosteroid or antimicrobial therapy), or a severe exacerbation (exacerbation of COPD symptoms required hospitalization). The number of participants who experienced 0, 1, 2, and >=3 exacerbation(s) was summarized.


Enrollment: 56
Study Start Date: May 2012
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ADOAIR250
ADOAIR 250mcg inhalations, twice daily, from week0 - 12
Drug: ADOAIR250
250 mcg inhalation, twice daily, from week0 -12.
Placebo Comparator: Placebo
Placebo inhalation, twice daily, from week0 -12
Drug: Placebo
Placebo inhalation, twice daily, from week0 -12.

Detailed Description:

This is a randomised, double-blind, placebo-controlled, two-arm, parallel-group, 12-week-treatment study in Japanese patients with COPD.

At Visit 1, patients confirmed to be fulfilling all the inclusion criteria and not meeting any of the exclusion criteria will start the 4-week run-in period. During the entire study period, including the run-in period, the only drug allowed to use in addition to the study drug will be oxitropium (short-acting anticholinergic drug) as relief medication. At the end of the run-in period (Visit 2), subjects eligible for randomisation will be evenly randomised to one of the following two treatment groups and start the 12-week treatment period.

  • ADOAIR®250 one inhalation twice daily from the DISKUS inhaler
  • Placebo one inhalation twice daily from the DISKUS inhaler

Study completers will be defined as subjects who have completed all examinations, assessments, and study procedures in the study period, including the run-in period and the follow-up period. At completion/discontinuation of the treatment period, subjects will be switched to appropriate COPD treatment at the discretion of the investigator (or subinvestigator).

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Japanese (male or female) outpatients aged 40-80 years inclusive at Visit 1 (Female patients may be enrolled only if they are not of child-bearing potential, or are of child-bearing potential who agree to properly use protocol-specified contraceptive measures. )
  2. Have a diagnosis of COPD (defined as per the COPD guideline)
  3. Have a FEV1/FVC ratio < 0.70 at 15-60 minutes following use of SALTANOL® INHALER
  4. Have a FEV1 of >= 40% to < 80% of the predicted normal value at 15-60 minutes following use of SALTANOL® INHALER
  5. Current or ex-smokers with a smoking history of at least 10 pack-years
  6. Able to use the DISKUS inhaler and the short-acting inhaled anticholinergic drug
  7. Capable of providing written voluntary consent to participate in the study

Exclusion Criteria:

  1. Diagnosed by the investigator (or subinvestigator) as having bronchial asthma
  2. Have any respiratory disorder other than COPD (e.g., lung cancer, sarcoidosis, tuberculosis [including old tuberculosis], pulmonary fibrosis)
  3. Have a chest X-ray (or CT scan) indicating a diagnosis other than COPD that might interfere with assessments in the study (This must be assessed using last imaging study performed within 6 months prior to Visit 1; or, a chest X-ray must be obtained at Visit 1.)
  4. Have chronic respiratory failure
  5. Have undergone lung volume reduction and/or lung transplant
  6. Have had a COPD exacerbation or respiratory infection requiring systemic corticosteroid or microbial therapy or hospitalisation, within 6 weeks prior to Visit 1
  7. Have used inhaled corticosteroids and systemic corticosteroids within 4 weeks prior to Visit 1
  8. Have used long-acting β2 agonists (inhaled or patch) within 2 weeks prior to Visit 1
  9. Are unable to stop their short-acting β2 agonist therapy at Visit 1 (During the study participation, oxitropium bromide (TERSIGAN) will be used as relief medication.)
  10. Receiving long-term oxygen therapy with oxygen use for more than 12 hours per day
  11. Have a concurrent serious or uncontrolled disease that might interfere with assessments in the study (including psychiatric disease, unstable liver disease, and heart disease)
  12. Have a QTc > 450 msec (or > 480 msec in patients with bundle branch block) at Visit 1 (based on average QTc from three consecutive cardiac cycles on ECG)
  13. Have participated in another study and received any other study drug within 4 weeks prior to Visit 1
  14. Diagnosed by the investigator (or subinvestigator) as having drug or alcohol dependence
  15. Have known or suspected hypersensitivity to bronchodilators, inhaled corticosteroid, or lactose
  16. Have known α1 antitrypsin deficiency
  17. Previously enrolled in this study
  18. Judged by the investigator (or subinvestigator) to be inappropriate to participate in this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01607398

Locations
Japan
GSK Investigational Site
Osaka, Japan, 530-0001
GSK Investigational Site
Osaka, Japan, 559-0011
GSK Investigational Site
Osaka, Japan, 545-8586
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01607398     History of Changes
Other Study ID Numbers: 116571
Study First Received: May 10, 2012
Results First Received: March 6, 2014
Last Updated: April 24, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by GlaxoSmithKline:
Japan
COPD
CAT
placebo
serum
Adoair250
anti-inflammatory
sputum

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 10, 2014