Long-term Safety Study for GSK573719/GW642444 in Japanese (DB2115362)

• ClinicalTrials.gov Identifier: NCT01376388
• Recruitment Status: Completed
• First Posted: June 20, 2011
• Results First Posted: March 14, 2014
• Last Update Posted: January 9, 2017
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

The objective of this study is to evaluate the safety and tolerability of GSK573719/GW642444 Inhalation Powder 125/25 mcg once-daily. The product will be delivered via the Novel Dry Powder Inhaler (nDPI) over 52 weeks to Japanese subjects with Chronic Obstructive Pulmonary Disease (COPD). This is a multi-centre, open-label study evaluating the safety of GSK573719/GW642444 Inhalation Powder 125/25 mcg. Treatment will be given once-daily in the morning. The target enrolment is approximately 120 subjects at approximately 20 study centres in Japan. The total duration of subject participation will be 54-55 weeks, consisting of a 7-14 day run-in period, 52-week treatment period and 1-week follow-up period. Subjects meeting all of the inclusion criteria and none of the exclusion criteria at screening visit (Visit 1) will enter 7-14 day run-in period. The run-in period is provided for completion of baseline safety evaluations and to obtain baseline measures of COPD status. At Visit 2, eligible subjects will start to take GSK573719/GW642444 125/25 mcg, and enter the treatment period. This treatment will be delivered via the Novel Dry Powder Inhaler (nDPI) once daily in the morning for 52 weeks. One nDPI will contain 30 doses of study medication. Subjects will be instructed to administer medication once daily in the morning for the duration of the 52-week treatment period. Each subject should be advised to adhere to this dosing regimen throughout the study. There will be a total of 8 study visits including at screening (Visit 1), initiation of treatment (Visit 2), and at 4weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, 52 weeks (Visit 3 through Visit 8, respectively). Follow-up (Visit 9) will be conducted by the phone contact approximately 1 week following the completion/withdrawal of treatment period. A subject will be considered to have completed the study upon completion of the last on-treatment visit (Visit 8). At the end of the treatment period, subjects will be prescribed appropriate COPD medication at the investigator's discretion.

Condition or disease	Intervention/treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: GSK573719/GW642444 Inhalation Powder	Phase 3

Detailed Description:

The objective of this study is to evaluate the safety and tolerability of GSK573719/GW642444 Inhalation Powder 125/25 mcg once-daily. The product will be delivered via the Novel Dry Powder Inhaler (nDPI) over 52 weeks to Japanese subjects with Chronic Obstructive Pulmonary Disease (COPD). This is a multi-centre, open-label study evaluating the safety of GSK573719/GW642444 Inhalation Powder 125/25 mcg. Treatment will be given once-daily in the morning. The target enrolment is approximately 120 subjects at approximately 20 study centres in Japan. The total duration of subject participation will be 54-55 weeks, consisting of a 7-14 day run-in period, 52-week treatment period and 1-week follow-up period. Subjects meeting all of the inclusion criteria and none of the exclusion criteria at screening visit (Visit 1) will enter 7-14 day run-in period. The run-in period is provided for completion of baseline safety evaluations and to obtain baseline measures of COPD status. Cardiovascular medical history/risk factors will be assessed at baseline. The following information will be collected from subjects receiving study medication and recorded in the eCRF: demography (including gender, ethnic origin and date of birth, height, weight), medical history (including duration of COPD and smoking history), COPD exacerbation assessment (documented history of ≥1 COPD exacerbation that required antibiotics/systemic corticosteroids or hospitalization in the past 12 months), concurrent medical conditions, and concomitant medication. At Visit 2, eligible subjects will start to take GSK573719/GW642444 125/25 mcg, and enter the treatment period. This treatment will be delivered via the Novel Dry Powder Inhaler (nDPI) once daily in the morning for 52 weeks. One nDPI will contain 30 doses of study medication. Subjects will be instructed to administer medication once daily in the morning for the duration of the 52-week treatment period. Each subject should be advised to adhere to this dosing regimen throughout the study. There will be a total of 8 study visits including at screening (Visit 1), initiation of treatment (Visit 2), and at 4weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks, 52 weeks (Visit 3 through Visit 8, respectively). Follow-up (Visit 9) will be conducted by the phone contact approximately 1 week following the completion/withdrawal of treatment period. A subject will be considered to have completed the study upon completion of the last on-treatment visit (Visit 8). At the end of the treatment period, subjects will be prescribed appropriate COPD medication at the investigator's discretion. Primary endpoint is incidence and severity of adverse events. Secondary endpoints are clinical laboratory tests (hematology, clinical chemistry), change from baseline in vital signs (pulse rate and systolic and diastolic pressure), and 12-lead Electrocardiogram (ECG) assessments. And other endpoints are change from baseline in trough Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC), number of puffs of supplemental use of salbutamol, percentage of rescue-free days, percentage of symptom-free days, mean symptom scores, incidence of COPD exacerbations, and COPD device preference questionnaire.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 131 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 52-week, Multi-centre, Open-label Study to Evaluate the Safety and Tolerability of GSK573719 125 mcg Once-daily in Combination With GW642444 25 mcg Once-daily Via Novel Dry Powder Inhaler (nDPI) in Japanese Subjects With Chronic Obstructive Pulmonary Disease.
• Study Start Date: August 2011
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: GSK573719/GW642444; 125/25mcg	Drug: GSK573719/GW642444 Inhalation Powder; GSK573719/GW642444 inhalation powder inhaled orally once daily for 52 weeks.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Throughout the Treatment Period [ Time Frame: 52 weeks ]
   An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs (occuring at a frequency threshold of >=5%) and SAEs.
2. Number of Participants With AEs Classified by the Indicated Maximum Grade Throughout the Treatment Period [ Time Frame: 52 weeks ]
   An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs were classified according to intensity based upon the investigators' clinical judgment. The intensity was categorized as: mild (an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities); moderate (an event that is sufficiently discomforting to interfere with normal everyday activities); or severe (an event that prevents normal everyday activities).

Secondary Outcome Measures :

1. Basophil, Eosinophil, Lymphocyte, Monocyte, and Total Neutrophil Values at Baseline (BL; Week -2), Week 12, Week 24, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD [ Time Frame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
   Blood samples were collected for the measurement of the indicated laboratory parameters at following time points: BL (Week -2), Week 12, Week 24, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 visit or withdrew before Week 52). The Baseline value for clinical laboratory tests was the value recorded on Week -2 (Screening visit).
2. Eosinophil Values, Total Neutrophil Values, Platelet Count, and White Blood Cell (WBC) Count at Baseline (BL; Week -2), Week 12, Week 24, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD [ Time Frame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
   Blood samples were collected for the measurment of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 visit or withdrew before Week 52). The Baseline value for clinical laboratory tests was the value recorded on Week -2 (Screening visit).
3. Hemoglobin, Albumin, and Total Protein Values at Baseline (BL; Week -2), Week 12, Week 24, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/Withdrawal (WD) [ Time Frame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
   Blood samples were collected for the measurement of hemoglobin, albumin, and total protein at the following time points: BL (Week -2), Week 12, Week 24, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 visit or withdrew before Week 52). The Baseline value for clinical laboratory tests was the value recorded on Week -2 (Screening visit).
4. Hematocrit Values at Baseline (BL; Week -2), Week 12, Week 24, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD [ Time Frame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
   Blood samples were collected for the measurement of hematocrit at the following time points: BL (Week -2), Week 12, Week 24, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 visit or withdrew before Week 52). The Baseline value for clinical laboratory tests was the value recorded on Week -2 (Screening visit).
5. Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase, and Gamma Glutamyl Transferase (GGT) Values at Baseline (BL; Week -2), Week 12, Week 24, Week 52, the WD Visit, Week 24/WD, and Week 52/WD [ Time Frame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
   Blood samples were collected for the measurement of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 visit or withdrew before Week 52). The Baseline value for clinical laboratory tests was the value recorded on Week -2 (Screening visit).
6. Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid Values at Baseline (BL; Week -2), Week 12, Week 24, Week 52, the WD Visit, Week 24/WD, and Week 52/WD [ Time Frame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
   Blood samples were collected for the measuremnt of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 visit or withdrew before Week 52). The Baseline value for clinical laboratory tests was the value recorded on Week -2 (Screening visit).
7. Calcium, Chloride, Glucose, Carbon Dioxide/Bicarbonate (CO2/HCO3), Potassium, Sodium, Phosphorous Inorganic, and Urea/Blood Urea Nitrogen (Urea/BUN) Values at Baseline (BL; Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD [ Time Frame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
   Blood samples were collected for the measurement of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 visit or withdrew before Week 52). The Baseline value for clinical laboratory tests was the value recorded on Week -2 (Screening visit).
8. Change From Baseline in Blood Pressure [ Time Frame: Baseline (Week 0), Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
   Blood pressure measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Blood pressure was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline was calculated as the assessment value at the time of interest minus the Baseline value. The WD visit was conducted for participants who withdrew at any point during the study. The Week 24/WD visit was conducted for participants who completed the Week 24 visit or withdrew before Week 24. The Week 52/WD visit was conducted for participants who completed the Week 52 visit or withdrew before Week 52.
9. Change From Baseline in Heart Rate [ Time Frame: Baseline (Week 0), Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
   Heart rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from Baseline was calculated as the assessment value at the time of interest minus the Baseline value. The WD visit was conducted for participants who withdrew at any point during the study. The Week 24/WD visit was conducted for participants who completed the Week 24 visit or withdrew before Week 24. The Week 52/WD visit was conducted for participants who completed the Week 52 visit or withdrew before Week 52.
10. Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points [ Time Frame: Baseline (Screening visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD ]
    A 12-lead ECG was recorded in a supine position after the participant was kept at rest in this position for at least 5 minutes. Data are presented as clinically significant (CS) or not clinically significant (NCS) abnormal findings. An abnormal and significant ECG finding includes the presence of a QT interval corrected for heart rate (QTc interval) >500 milliseconds (msec) or an uncorrected QT interval >600 msec, for participants with Bundle Branch Block QTc >530 msec based on an average QTc value of triplicate ECGs. The study investigator determined if the abnormal ECG finding was CS or NCS. The WD visit was conducted for participants who withdrew at any point during the study. The Week 24/WD and Week 52/WD visits were conducted for participants who completed the Week 24 visit or withdrew before Week 24 and completed the Week 52 visit or withdrew before Week 52, respectively. The Baseline value for clinical laboratory tests was the value recorded on Week -2 (Screening visit).

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Outpatient.
• A signed and dated written informed consent prior to study participation.
• Japanese subjects 40 years of age or older at screening.
• Male or female subjects (female subjects who have child bearing potential has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods used consistently and correctly).
• Diagnosis of COPD.
• 10 pack-year or greater history of cigarette smoking.
• Post-bronchodilator FEV1/FVC of <0.7.
• Predicted FEV1 of <80%.

Exclusion Criteria:

• Women who are pregnant or lactating or are planning on becoming pregnant during the study.
• A current diagnosis of asthma.
• Respiratory disorders other than COPD.
• Clinically significant non-respiratory diseases or abnormalities that are not adequate controlled.
• 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 history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate or a medical condition.
• Hospitalization for COPD or pneumonia within 12 weeks prior to screening.
• Subjects with lung volume reduction surgery within the 12 months prior to screening.
• Abnormal and clinically significant ECG findings at screening.
• Significantly abnormal finding from clinical chemistry or hematology, tests at screening.
• Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day.
• Regular use (prescribed every day, not for as-needed use) of short-acting bronchodilators via nebulized therapy.
• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to screening.
• A know or suspected history of alcohol or drug abuse within 2 years prior to screening.
• Affiliation with the investigational site.
• Previous use of GSK573719, GW642444, the GSK573719/GW642444 combination or the Fluticasone Furoate/GW642444 combination.
• Use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer).

Contacts and Locations

Locations

Japan

GSK Investigational Site

Fukuoka, Japan, 802-0083

GSK Investigational Site

Gunma, Japan, 371-0048

GSK Investigational Site

Hiroshima, Japan, 732-0052

GSK Investigational Site

Hiroshima, Japan, 732-0057

GSK Investigational Site

Hokkaido, Japan, 064-0915

GSK Investigational Site

Hokkaido, Japan, 080-0805

GSK Investigational Site

Hyogo, Japan, 665-0827

GSK Investigational Site

Hyogo, Japan, 670-0849

GSK Investigational Site

Ibaraki, Japan, 300-0053

GSK Investigational Site

Kagawa, Japan, 763-8502

GSK Investigational Site

Kanagawa, Japan, 239-0821

GSK Investigational Site

Kyoto, Japan, 615-8087

GSK Investigational Site

Oita, Japan, 870-0921

GSK Investigational Site

Oita, Japan, 876-0047

GSK Investigational Site

Osaka, Japan, 576-0016

GSK Investigational Site

Osaka, Japan, 589-0022

GSK Investigational Site

Osaka, Japan, 590-0064

GSK Investigational Site

Shizuoka, Japan, 436-0022

GSK Investigational Site

Tokyo, Japan, 105-0004

GSK Investigational Site

Tokyo, Japan, 185-0014

GSK Investigational Site

Tokyo, Japan, 187-0024

GSK Investigational Site

Wakayama, Japan, 641-8510

GSK Investigational Site

Yamanashi, Japan, 400-0031

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research. 

Study Data/Documents: Statistical Analysis Plan 

Identifier: 115362
For additional information about this study please refer to the GSK Clinical Study Register

Individual Participant Data Set 

Identifier: 115362
For additional information about this study please refer to the GSK Clinical Study Register

Dataset Specification 

Identifier: 115362
For additional information about this study please refer to the GSK Clinical Study Register

Annotated Case Report Form 

Identifier: 115362
For additional information about this study please refer to the GSK Clinical Study Register

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01376388
• Other Study ID Numbers: 115362
• First Posted: June 20, 2011
• Results First Posted: March 14, 2014
• Last Update Posted: January 9, 2017
• Last Verified: November 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:

Chronic Obstructive Pulmonary Disease (COPD); Pharmacogenetics; GSK573719/GW642444

Additional relevant MeSH terms:

Lung Diseases; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Lung Diseases, Obstructive