A Phase III, Randomized, Double-blind, Active Controlled, Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Combination FF/UMEC/VI With the Fixed Dose Dual Combination of FF/VI, Administered Once-daily Via a Dry Powder Inhaler in Subjects With Inadequately Controlled Asthma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,436
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 24
研究概览
简要总结
A once-daily 'closed' triple FDC therapy of FF/UMEC/VI via a single ELLIPTA® dry powder inhaler (DPI) is being developed by GlaxoSmithKline (GSK) 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 is a phase III, multi-center, active-controlled, double-blind, parallel-group study to compare the efficacy, safety and tolerability of the FDC of FF/UMEC/VI with the FDC of FF/VI. This study has 5 phases: Pre-Screening (Visit 0), Screening/Run-in, Enrolment/Stabilization, Randomization/Treatment, and Follow up. At Visit 1 (Screening), subjects meeting all protocol defined inclusion/exclusion criteria will enter a 3-week run-in period and will receive fixed dose inhaled corticosteroid/long-acting beta agonist (ICS/LABA) (fluticasone/salmeterol, 250/50 micrograms (mcg), via the DISKUS® DPI) one inhalation twice a day. At Visit 2 (Enrolment), eligible subjects will be enrolled into the 2-week stabilization period to receive FF/VI (100/25 mcg via the ELLIPTA DPI once a day, in the morning). At the conclusion of the stabilization period (Visit 3), all subjects who meet the pre-defined randomization criteria will be randomized 1:1:1:1:1:1 during the treatment period to receive either FF/UMEC/VI (100/62.5/25 mcg; 200/62.5/25 mcg; 100/31.25/25 mcg; 200/31.25/25 mcg) or FF/VI (100/25 mcg; 200/25 mcg) via the ELLIPTA DPI once daily in the morning. The duration of the treatment period is variable but will be a minimum of 24 weeks and a maximum of 52 weeks. Subjects will have up to 6 on-treatment clinic visits scheduled at Visits 3, 4, 5, 6, 7 and 8/End of Study (EOS) (Weeks 0, 4, 12, 24, 36 and 52, respectively). A follow-up visit will be conducted approximately 7 days after the end of treatment period or, if applicable, after the early withdrawal visit. Subjects will be provided with short acting albuterol/salbutamol to be used on an as-needed basis (rescue medication) throughout the study. Approximately 2250 subjects will be randomized, with approximately 375 subjects randomized to each of the 6 double-blind treatment arms to ensure approximately 337 evaluable subjects per treatment arm. DISKUS and ELLIPTA are registered trademarks of GSK groups of companies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
FF/UMEC/VI (100/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/UMEC/VI (100/31.25/25) mcg (Drug)
FF/UMEC/VI (100/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/VI (100/25) mcg (Drug)
FF/UMEC/VI (100/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Fluticasone/salmeterol (FSC) (Drug)
FF/UMEC/VI (100/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Albuterol/salbutamol (Drug)
FF/UMEC/VI (100/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: ELLIPTA DPI (Device)
FF/UMEC/VI (100/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: DISKUS DPI (Device)
FF/UMEC/VI (100/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: METERED-DOSE INHALER (MDI) (Device)
FF/UMEC/VI (100/62.5/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects will also receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/UMEC/VI (100/62.5/25) mcg (Drug)
FF/UMEC/VI (100/62.5/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects will also receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/VI (100/25) mcg (Drug)
FF/UMEC/VI (100/62.5/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects will also receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Fluticasone/salmeterol (FSC) (Drug)
FF/UMEC/VI (100/62.5/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects will also receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Albuterol/salbutamol (Drug)
FF/UMEC/VI (100/62.5/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects will also receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: ELLIPTA DPI (Device)
FF/UMEC/VI (100/62.5/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects will also receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: DISKUS DPI (Device)
FF/UMEC/VI (100/62.5/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (100/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects will also receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: METERED-DOSE INHALER (MDI) (Device)
FF/UMEC/VI (200/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (200/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/UMEC/VI (200/31.25/25) mcg (Drug)
FF/UMEC/VI (200/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (200/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/VI (100/25) mcg (Drug)
FF/UMEC/VI (200/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (200/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Fluticasone/salmeterol (FSC) (Drug)
FF/UMEC/VI (200/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (200/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Albuterol/salbutamol (Drug)
FF/UMEC/VI (200/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (200/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: ELLIPTA DPI (Device)
FF/UMEC/VI (200/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (200/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: DISKUS DPI (Device)
FF/UMEC/VI (200/31.25/25) mcg closed triple therapy
Subjects will receive FF/UMEC/VI (200/31.25/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: METERED-DOSE INHALER (MDI) (Device)
FF/UMEC/VI (200/62.5/25) mcg closed triple therapy
Subjects may receive FF/UMEC/VI (200/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/UMEC/VI (200/62.5/25) mcg (Drug)
FF/UMEC/VI (200/62.5/25) mcg closed triple therapy
Subjects may receive FF/UMEC/VI (200/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/VI (100/25) mcg (Drug)
FF/UMEC/VI (200/62.5/25) mcg closed triple therapy
Subjects may receive FF/UMEC/VI (200/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Fluticasone/salmeterol (FSC) (Drug)
FF/UMEC/VI (200/62.5/25) mcg closed triple therapy
Subjects may receive FF/UMEC/VI (200/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Albuterol/salbutamol (Drug)
FF/UMEC/VI (200/62.5/25) mcg closed triple therapy
Subjects may receive FF/UMEC/VI (200/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: ELLIPTA DPI (Device)
FF/UMEC/VI (200/62.5/25) mcg closed triple therapy
Subjects may receive FF/UMEC/VI (200/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: DISKUS DPI (Device)
FF/UMEC/VI (200/62.5/25) mcg closed triple therapy
Subjects may receive FF/UMEC/VI (200/62.5/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: METERED-DOSE INHALER (MDI) (Device)
FF/VI (100/25) mcg dual combination therapy
Subjects will receive FF/VI (100/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/VI (100/25) mcg (Drug)
FF/VI (100/25) mcg dual combination therapy
Subjects will receive FF/VI (100/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Fluticasone/salmeterol (FSC) (Drug)
FF/VI (100/25) mcg dual combination therapy
Subjects will receive FF/VI (100/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Albuterol/salbutamol (Drug)
FF/VI (100/25) mcg dual combination therapy
Subjects will receive FF/VI (100/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: ELLIPTA DPI (Device)
FF/VI (100/25) mcg dual combination therapy
Subjects will receive FF/VI (100/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: DISKUS DPI (Device)
FF/VI (100/25) mcg dual combination therapy
Subjects will receive FF/VI (100/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: METERED-DOSE INHALER (MDI) (Device)
FF/VI (200/25) mcg dual combination therapy
Subjects will receive FF/VI (200/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/VI (100/25) mcg (Drug)
FF/VI (200/25) mcg dual combination therapy
Subjects will receive FF/VI (200/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: FF/VI (200/25) mcg (Drug)
FF/VI (200/25) mcg dual combination therapy
Subjects will receive FF/VI (200/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Fluticasone/salmeterol (FSC) (Drug)
FF/VI (200/25) mcg dual combination therapy
Subjects will receive FF/VI (200/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: Albuterol/salbutamol (Drug)
FF/VI (200/25) mcg dual combination therapy
Subjects will receive FF/VI (200/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: ELLIPTA DPI (Device)
FF/VI (200/25) mcg dual combination therapy
Subjects will receive FF/VI (200/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: DISKUS DPI (Device)
FF/VI (200/25) mcg dual combination therapy
Subjects will receive FF/VI (200/25) mcg inhalation powder via DPI, once daily in the morning. Subjects may receive albuterol/salbutamol as a rescue medication when needed during the treatment period.
干预措施: METERED-DOSE INHALER (MDI) (Device)
结局指标
主要结局
Mean Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 24
时间窗: Baseline (pre-dose at Day 1) and Week 24
FEV1 is a measure of lung function and is defined as the maximal volume of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the highest FEV1 value obtained prior to the morning dose of investigational product. Baseline value is the last acceptable/borderline acceptable pre-dose FEV1 prior to randomized treatment start date (pre-dose at Day 1). Change from Baseline value is the value at Week 24 minus the Baseline value. Intent-to-Treat (ITT) Population comprised of all randomized participants, excluding those who were randomized in error, who did not receive the study drug. Treatment policy estimand was assessed, including all on- and post-treatment data. Different participants may have been analyzed at different time points; thus, overall number of participants analyzed reflects everyone in ITT Population without missing covariate information, with Baseline and at least one post-baseline measurement. Mixed Model Repeated Measures(MMRM) was used.
次要结局
- Annualized Rate of Moderate and Severe Asthma Exacerbations(Up to Week 52)
- Mean Change From Baseline in Clinic FEV1 at 3 Hours Post Study Treatment at Week 24(Baseline (pre-dose at Day 1) and 3 hours post dose at Week 24)
- Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score Over Weeks 21 to 24 (Inclusive) of the Treatment Period(Baseline (14 days prior to randomization) and Weeks 21 to 24)
- Number of Participants With Any Serious Adverse Event (SAE) and Common (>=3%) Non-SAE(Up to Week 52)
- Mean Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 24(Baseline (pre-dose at Day 1) and Week 24)
- Mean Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Week 24(Baseline (pre-dose at Day 1) and Week 24)
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings(Up to Week 52)
- Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24(Baseline (pre-dose at Day 1) and Week 24)
- Mean Change From Baseline in Pulse Rate at Week 24(Baseline (pre-dose at Day 1) and Week 24)
- Number of Participants With Abnormal Clinical Chemistry Values(Up to Week 52)
- Number of Participants With Abnormal Hematology Values(Up to Week 52)