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A Long-term Safety Study of Fixed Dose Combination Therapy Fluticasone Furoate/Umeclidinium Bromide/Vilanterol Trifenatate in Japanese Subjects With Asthma

Phase 3
Completed
Conditions
Asthma
Interventions
Drug: FF/UMEC/VI 100/62.5/25 mcg
Drug: FF/UMEC/VI 200/62.5/25 mcg
Drug: Salbutamol
Other: ACQ-7
Registration Number
NCT03184987
Lead Sponsor
GlaxoSmithKline
Brief Summary

Despite availability of treatments and published guidelines, subjects may have asthma that is inadequately controlled. GlaxoSmithKline is currently developing a once-daily 'closed' triple therapy of an Inhaled Corticosteroids/Long-Acting Beta-2-Agonists/Long-Acting Muscarinic Antagonist (ICS/LAMA/LABA) combination (Fluticasone Furoate/Umeclidinium Bromide/Vilanterol Trifenatate \[FF/UMEC/VI\]) in a single device, with the aim of providing a new treatment option for the management of asthma by improving lung function, health-related quality of life (HRQoL) and symptom control over established combination therapies. This study has 3 study periods: Run-in, Treatment period and a Follow-up period. Eligible subjects who meet the pre-defined criteria at screening (Visit 1) will enter into a 2-week run-in period. Subjects will continue their pre-screening inhaled medications for asthma (ICS+LABA or ICS+LABA+LAMA) without any change in regimen/dosage until day before Visit 2. At Visit 2 subjects will be allocated to either FF/UMEC/VI 100/62.5/25 or FF/UMEC/VI 200/62.5/25 micrograms (mcg) treatment depending on the asthma control status for 52 weeks. Switching medication from FF/UMEC/VI 100/62.5/25 to FF/UMEC/VI 200/62.5/25 will be permitted in accordance with the control status of the subject assessed by Asthma Control Questionnaire (ACQ)-7 at Week 24 of the treatment period. A follow-up visit will be conducted for approximately 1 week. Subjects will be provided with salbutamol as a rescue medication throughout the study.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
111
Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
FF/UMEC/VI 100/62.5/25 mcg closed triple therapyFF/UMEC/VI 100/62.5/25 mcgSubjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
FF/UMEC/VI 100/62.5/25 mcg closed triple therapySalbutamolSubjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
FF/UMEC/VI 100/62.5/25 mcg closed triple therapyACQ-7Subjects will receive FF/UMEC/VI 100/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
FF/UMEC/VI 200/62.5/25 mcg closed triple therapyFF/UMEC/VI 200/62.5/25 mcgSubjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
FF/UMEC/VI 200/62.5/25 mcg closed triple therapySalbutamolSubjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
FF/UMEC/VI 200/62.5/25 mcg closed triple therapyACQ-7Subjects will receive FF/UMEC/VI 200/62.5/25 mcg inhalation powder via ELLIPTA, once daily, 1 puff/time, in the morning. Subjects may receive salbutamol as a rescue medication when needed throughout the run-in and treatment period.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)Up to Week 52

An adverse event (AE) is any untoward medical occurrence in clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose: result in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect, other important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcome mentioned before. Intent-To-Treat (ITT) Population comprised of all participants who received at least one dose of study treatment in the treatment period.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)Baseline (Day 1), Weeks 4, 12, 24, 36 and 52

Blood pressure was measured in seated position after 5 minutes rest for participants at indicated time points. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Pulse RateBaseline (Day 1), Weeks 4, 12, 24, 36 and 52

Pulse rate was measured in seated position after 5 minutes rest for participants at indicated time points. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in PR Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF)Baseline (Day 1), Weeks 4, 24 and 52

Single 12-lead electrocardiograms (ECG) were obtained using an automated ECG machine that measured PR Interval and QTcF Interval. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular HemoglobinBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular VolumeBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: ErythrocytesBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: HematocritBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: HemoglobinBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Platelet CountBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: platelet count. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Basophils/LeukocytesBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: Basophils/Leukocytes. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Eosinophils/LeukocytesBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: Eosinophils/Leukocytes. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Lymphocytes/LeukocytesBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: Lymphocytes/Leukocytes. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Monocytes/LeukocytesBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: Monocytes/Leukocytes. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Hematology Parameter: Neutrophils/LeukocytesBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the hematology parameter: Neutrophils/Leukocytes. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate AminotransferaseBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the chemistry parameters: alanine aminotransferase, alkaline phosphatase and aspartate aminotransferase. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Chemistry Parameters: Albumin, ProteinBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the chemistry parameters: albumin and protein. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct BilirubinBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the chemistry parameters: bilirubin, creatinine and direct bilirubin. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium, UreaBaseline (Day 1), Weeks 12, 24 and 52

Blood samples were collected to analyze the chemistry parameters: calcium, glucose, potassium, sodium and urea. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as relevant visit value minus Baseline value.

Number of Participants With Worst Case Post-Baseline Urinalysis Results Relative to BaselineBaseline (Day 1) and up to Week 52

Urine samples were collected for analysis of presence of occult blood and protein in urine using dipstick method. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of occult blood and protein can be read as Trace, 1+, 2+ and 3+ indicating proportional concentrations in the urine sample. Baseline is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Trial Locations

Locations (1)

GSK Investigational Site

🇯🇵

Toyama, Japan

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