A 24-week Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 125/25 mcg and 62.5/25mcg Inhalation Powder Compared With Placebo in Subjects With COPD

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01636713
First received: July 5, 2012
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

This is a 24-week, phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group study. The study will have 9 scheduled visits and a telephone contact Follow-up visit one week following the end of study treatment.

The study primary endpoint is

-Clinic visit trough (pre-bronchodilator and pre-dose) FEV1 on Treatment Day 169 Trough FEV1 on Treatment Day 169 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Treatment Day 168 (i.e. at the Week 24 visit).

Secondary endpoints are;

  • Mean TDI focal score at Week 24
  • Weighted mean clinic visit FEV1 over 0 to 6 hours post-dose at Visit 2 (Day 1)

Eligible subjects will be randomised to GSK573719/GW642444 125/25mcg, GSK573719/GW642444 62.5/25mcg and placebo treatment groups in a 1:1:1 ratio such that of the planned 573 total number of randomised subjects, approximately 191 subjects will be randomised to each active treatment group and 191 subjects will be randomised to placebo. All treatments will be administered once daily in the morning by inhalation using a Novel Dry Powder Inhaler (NDPI).

There will be a total of 9 study clinic visits conducted on an outpatient basis. Subjects who meet the eligibility criteria at Screening (Visit.1) will complete a 7 to 14 day Run-In period followed by a 24-week Treatment period. Clinic visits will be at screening, Randomisation (Day1), Day2, after 4, 8, 12, 16, and 24-weeks of treatment, and 1 day after the Week 24 Visit (also referred as Treatment Day 169). A Follow-Up contact for adverse event assessment will be conducted by telephone approximately 7 days after Visit 9 or the Early Withdrawal Visit. The total duration of subject participation, including Follow-up will be approximately 27 weeks. All subjects will be provided with albuterol/salbutamol for use on an "as-needed" basis throughout the Run-In and Study Treatment Periods.

At screening, pre-bronchodilator spirometry will be performed followed by post-albuterol/salbutamol spirometry testing. Post-albuterol/salbutamol FEV1 and FEV1/FVC values will be used to determine subject eligibility. To further characterise bronchodilator responsiveness, post ipratropium testing will be conducted following completion of post-albuterol/salbutamol spirometry.

Spirometry will be conducted at each post-randomisation clinic visit. Six hour post-dose serial spirometry will be conducted at Visit 2. Trough spirometry will be obtained 23 and 24 hours after the previous day's dose of blinded study medication at Visits 3 to 9.

Assessments of dyspnea will be obtained using the Baseline and Transition Dyspnoea Index (BDI/TDI) which is an interviewer based instrument. At Visit 2, the severity of dyspnoea at baseline will be assessed using the BDI. At subsequent visits (Visits 4, 6, and 8) change from baseline will be assessed using the TDI. Administration of the BDI and TDI should be done prior to spirometry and any other study-related procedures Disease specific health status will be evaluated using the St. George's Respiratory Questionnaire (SGRQ) and COPD Assessment Test (CAT), at baseline (Visit 2) and Visits 4, 6 and 8.

The occurrence of adverse events will be evaluated throughout the study beginning at Visit 2. SAEs will be collected over the same time period as for AEs. However, any SAEs assessed as related to study participation (e.g., study treatment, protocol-mandated procedures, invasive tests, or change in existing therapy) or related to a GSK concomitant medication, will be recorded from the time a subject consents to participate in the study up to and including any follow up contact.

Vital signs (blood pressure and pulse rate), 12-lead ECGs and standard clinical laboratory tests (hematology and blood biochemistry) will be obtained at selected clinic visits.

For determination of subject disposition, subjects will be considered to have completed the study, upon completion of Visit 9. There is no plan to provide any of the active study treatments for compassionate use following study completion.

The Intent-to-Treat (ITT) population will be the primary population of interest, and is defined as all randomised subjects who have received at least one dose of the randomised study medication during the Treatment Period.

Supplementary study conduct information not mandated to be present in this protocol is provided in the accompanying Study Procedures Manual (SPM). The SPM will provide the site personnel with administrative and detailed technical information that does not impact subject safety.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: GSK573719/VI 62.5/25
Drug: GSK573719/VI 125/25
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 24-week Randomised, Double-blind and Placebo-controlled Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 125/25 mcg and 62.5/25mcg Inhalation Powder Compared With Placebo Inhalation Powder Delivered Once-daily Via a Novel Dry Powder Inhaler in 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 (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 169 (Week 24) [ Time Frame: Baseline and Day 169 ] [ Designated as safety issue: No ]
    FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84, 112, 168, and 169. Baseline is defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 169 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 168). Change from Baseline at a particular visit was calculated as the trough FEV1at that visit minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline, smoking status, country/region, day, day by Baseline and day by treatment interactions. par.=participants.


Secondary Outcome Measures:
  • Transition Dyspnea Index (TDI) Focal Score at Day 168 (Week 24) [ Time Frame: Day 168 (Week 24) ] [ Designated as safety issue: No ]
    The TDI is an interviewer-administered instrument which measures the changes in the participant's dyspnea from Baseline. This questionnaire was collected on Days 28, 84 and 168. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9. Analysis was performed using a repeated measures model with covariates of treatment, Baseline dyspnea index (BDI) focal score, smoking status, country/region, day, day by Baseline dyspnea index (BDI) focal score and day by treatment interactions.

  • Change From Baseline Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Day 1 [ Time Frame: Baseline and Day 1 ] [ Designated as safety issue: No ]
    FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated using the 0-6-hour post-dose FEV1 measurements collected on Day 1, which included pre-dose (30 minutes [min] and 5 min prior to dosing) and post-dose at 15 min, 30 min, 1 hour, 3 hours, and 6 hours. Change from Baseline at Day 1was calculated as the WM at post -dose value on Day 1 minus Baseline (mean of the two assessments made 30 min and 5 min pre-dose on Day 1). Analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of treatment, Baseline FEV1 (mean of the two assessments made 30 and 5 minutes pre-dose on Day 1), smoking status, and country/region.


Enrollment: 581
Study Start Date: July 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK573719/VI 62.5/25
Inhalation via Novel Dry Powder Inhaler Once a day
Drug: GSK573719/VI 62.5/25
Inhalation via Novel Dry Powder Inhaler Once a day
Experimental: GSK573719/VI 125/25
Inhalation via Novel Dry Powder Inhaler Once a day
Drug: GSK573719/VI 125/25
Inhalation via Novel Dry Powder Inhaler Once a day
Placebo Comparator: Placebo
Inhalation via Novel Dry Powder Inhaler Once a day
Drug: Placebo
Inhalation via Novel Dry Powder Inhaler Once a day

  Eligibility

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

Inclusion Criteria:

  1. Type of subject: outpatient.
  2. Informed Consent: A signed and dated written informed consent prior to study participation.
  3. Age: 40 years of age or older at Screening (Visit 1).
  4. Gender: Male or female subjects are eligible to participate in the study.
  5. COPD History: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004] as follows:
  6. Tobacco Use and Smoking History: Current or former cigarette smokers with a history of cigarette smoking of more than or equal to 10 pack-years
  7. Severity of Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a post-albuterol/salbutamol FEV1 of less than or equal to 70% of predicted normal values calculated using NHANES III reference equations at Visit 1 [Hankinson1999,Hankinson, 2010].
  8. Dyspnea: A score of ≥2 on the Modified Medical Research Council Dyspnoea Scale (mMRC) at Screening (Visit 2)

Exclusion Criteria:

  1. Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.
  2. Asthma: A current diagnosis of asthma.
  3. Other Respiratory Disorders: Known alpha-1 antitrypsin deficiency, active lung infections (such as tuberculosis) and lung cancer are absolute exclusionary conditions. A subject, who in the opinion of the investigator has any other significant respiratory conditions in addition to COPD should be excluded. Examples may include clinically significant, bronchiectasis, pulmonary hypertension, sarcoidosis or interstitial lung disease.
  4. Other Diseases/Abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled and/or a previous history of cancer in remission for < 5 years prior to Visit 1 (localized carcinoma of the skin that has been resected for cure is not exclusionary).
  5. Chest X-Ray: A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. A chest X-ray must be taken at Visit 1 if a chest X-ray or CT scan is not available within 6 months prior to Visit 1.
  6. Contraindications: A history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition such as of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that, in the opinion of the study physician contraindicates study participation or use of an inhaled anticholinergic.
  7. Hospitalization: Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1.
  8. Lung Resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1).
  9. 12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1, including the presence of a paced rhythm on a 12-lead electrocardiogram (ECG) which causes the underlying rhythm and ECG to be obscured. Investigators will be provided with ECG reviews conducted by a centralized independent cardiologist to assist in evaluation of subject eligibility.
  10. Screening Labs: Significantly abnormal finding from clinical chemistry and haematology tests at Visit 1.
  11. Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour period required prior to spirometry testing at each study visit.
  12. Medications prior to Screening: List are provided in the protocol
  13. Oxygen: Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. As-needed oxygen use (i.e., less than 12 hours per day) is not exclusionary.
  14. Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy.
  15. Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
  16. Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
  17. Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved 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: NCT01636713

  Hide Study Locations
Locations
China, Guangdong
GSK Investigational Site
Gaungzhou, Guangdong, China, 510120
GSK Investigational Site
Guangzhou, Guangdong, China, 510120
GSK Investigational Site
Zhanjiang, Guangdong, China, 524001
China, Guangxi
GSK Investigational Site
Nanning, Guangxi, China, 530021
China, Hunan
GSK Investigational Site
Changsha, Hunan, China, 410011
China, Jiangxi
GSK Investigational Site
Nanchang, Jiangxi, China, 330006
China, Jilin
GSK Investigational Site
Changchun, Jilin, China, 130041
China, Liaoning
GSK Investigational Site
Shenyang, Liaoning, China, 110015
GSK Investigational Site
Shenyang, Liaoning, China, 110001
GSK Investigational Site
Shenyang, Liaoning, China, 110004
China, Shaanxi
GSK Investigational Site
Xian, Shaanxi, China, 710061
GSK Investigational Site
Xian, Shaanxi, China, 710032
China, Shandong
GSK Investigational Site
Qingdao, Shandong, China, 266071
China, Shanxi
GSK Investigational Site
Taiyuan, Shanxi, China
China, Sichuan
GSK Investigational Site
Chengdu, Sichuan, China, 610072
China
GSK Investigational Site
Beijing, China, 100050
GSK Investigational Site
Beijing, China, 100048
GSK Investigational Site
Changsha, China, 410013
GSK Investigational Site
Chongqing, China, 400016
GSK Investigational Site
Chongqing, China
GSK Investigational Site
Chongqing, China, 400037
GSK Investigational Site
Chongqing, China, 400038
GSK Investigational Site
Shanghai, China, 200080
GSK Investigational Site
Wuxi, China, 214023
Korea, Republic of
GSK Investigational Site
Chonju, Korea, Republic of, 561-712
GSK Investigational Site
Gangdong-gu, Seoul, Korea, Republic of, 134060
GSK Investigational Site
Gyeonggi-do, Korea, Republic of, 410-719
GSK Investigational Site
Gyeonggi-do, Korea, Republic of, 431-070
GSK Investigational Site
Seoul, Korea, Republic of, 134-090
Philippines
GSK Investigational Site
Jaro, Iloilo City, Philippines, 5000
GSK Investigational Site
Quezon City, Philippines, 1101
GSK Investigational Site
Quezon City, Philippines, 1109
Taiwan
GSK Investigational Site
Changhua, Taiwan, 500
GSK Investigational Site
Kaohsiung Hsien, Taiwan, 833
GSK Investigational Site
Keelung, Taiwan, 20401
GSK Investigational Site
Taichung, Taiwan, 40705
GSK Investigational Site
Taichung, Taiwan, 404
GSK Investigational Site
Taichung, Taiwan, 40201
GSK Investigational Site
Taipei, Taiwan, 220
GSK Investigational Site
Taipei, Taiwan
GSK Investigational Site
Tau-Yuan County, Taiwan, 333
Thailand
GSK Investigational Site
Bangkok, Thailand, 10400
GSK Investigational Site
Khon Kaen, Thailand, 40002
GSK Investigational Site
Nan, Thailand, 55000
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01636713     History of Changes
Other Study ID Numbers: 114634
Study First Received: July 5, 2012
Results First Received: May 1, 2014
Last Updated: May 22, 2014
Health Authority: Korea: Food and Drug Administration

Additional relevant MeSH terms:
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Chronic Disease
Lung Diseases
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes

ClinicalTrials.gov processed this record on September 16, 2014