Clinical trial NCT01376388: Long-term Safety Study for GSK573719/GW642444 in Japanese
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Chronic Obstructive Pulmonary Disease (COPD)
Pharmacogenetics
GSK573719/GW642444
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-06-20
Enrollment: 131
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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).

Primary outcomes:
measure: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Throughout the Treatment Period
timeFrame: 52 weeks
measure: Number of Participants With AEs Classified by the Indicated Maximum Grade Throughout the Treatment Period
timeFrame: 52 weeks
Secondary outcomes:
measure: 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
timeFrame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: 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
timeFrame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: 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)
timeFrame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Hematocrit Values at Baseline (BL; Week -2), Week 12, Week 24, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD
timeFrame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: 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
timeFrame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: 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
timeFrame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: 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
timeFrame: BL (Screening visit: Week -2), Week 12, Week 24, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Change From Baseline in Blood Pressure
timeFrame: Baseline (Week 0), Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Change From Baseline in Heart Rate
timeFrame: Baseline (Week 0), Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
measure: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings at the Indicated Time Points
timeFrame: Baseline (Screening visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD
Other outcomes:
Locations:
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Gunma
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: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Oita
country: Japan
facility: GSK Investigational Site
city: Oita
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: 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: Wakayama
country: Japan
facility: GSK Investigational Site
city: Yamanashi
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: