A Randomized, Double-Blind, Parallel Group, Multicenter Study of Fluticasone Furoate/Vilanterol 200/25 mcg Inhalation Powder, Fluticasone Furoate/Vilanterol 100/25 mcg Inhalation Powder, and Fluticasone Furoate 100 mcg Inhalation Powder in the Treatment of Persistent Asthma in Adults and Adolescents
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,040
- 试验地点
- 1
- 主要终点
- Change From Baseline in Weighted Mean Forced Expiratory Volume in One Second (FEV1) Over 0 to 24 Hours Post-dose at the End of the 12-week Treatment Period
研究概览
简要总结
This is a Phase III, multicenter, randomized, double-blind, stratified, parallel-group study with three active comparators in subjects with moderate to severe persistent asthma. The study consists of a run-in period of 4 weeks, followed by a treatment period of 12 weeks, and a follow up contact period of one week. The total duration of the study is 17 weeks. 990 subjects will be randomized to one of three treatments (FF/VI Inhalation Powder 200/25 mcg once daily in the evening; FF/VI Inhalation Powder 100/25 mcg once daily in the evening; FF 100 Inhalation Powder once daily in the evening) for 12 weeks. In addition, all subjects will be supplied albuterol/salbutamol inhalation aerosol at Visit 1 to use as needed for acute asthma symptoms throughout the entire study. Subjects will attend four on-treatment visits at Weeks 2, 4, 8, and 12 (Visits 4 through 7).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must give their signed and dated (written) informed consent to participate. Written informed consent must be obtained if a subject's current medication is changed as a result of study participation
- •Outpatient >=12 years of age at Visit 1 who have had a diagnosis of asthma, as defined by the National Institutes of Health. Countries with local restrictions prohibiting enrolment of adolescents will only enroll subjects >=18 years of age
- •Male or an eligible female. Eligible female is defined as having non-childbearing potential or having childbearing potential and using an acceptable method of birth control consistently and correctly.
- •Best pre-bronchodilator FEV1 of 40% to 80% of their predicted normal value.
- •Demonstrate >=12% and >=200 mL reversibility of FEV1 within 10 to 40 minutes following 4 inhalations of albuterol/salbutamol inhalation aerosol (or an equivalent nebulized treatment with albuterol/salbutamol solution) or have documented reversibility testing within the 6 months prior to Visit 1 meeting this measure of reversibility. A spacer device may be used for testing, if required.
- •If subject have received ICS for at least 12 weeks prior to Visit 1 and their treatment during the 4 weeks immediately prior to Visit 1 consisted of either of the two regimens (a or b).a.) A stable mid-dose or high-dose of ICS alone (e.g., >=FP 250 mcg twice daily) or b.) A stable dose of a mid-dose ICS/LABA combination (e.g., FP/Salmeterol [SALM] 250/50 mcg twice daily) or an equivalent combination via separate inhalers.
- •Use of ICS/LABA are not permitted with LABA on the day of Visit
- •Must be able to replace current SABA treatment with albuterol/salbutamol aerosol inhaler at Visit 1 for use as needed, during the study. Subjects must be able to withhold albuterol/salbutamol for at least 6 hours prior to study visits
排除标准
- •History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures within the last 5 years.
- •Upper or lower respiratory tract, sinus, or middle ear that is: not resolved within 4 weeks of Visit 1 and led to a change in asthma management or, in the opinion of the investigator, expected to affect the subject's asthma status or the subject's ability to participate in the study.
- •Any asthma exacerbation that required oral corticosteroids within the 12 weeks prior to Visit 1 or, resulted in an overnight hospitalization requiring additional treatment for asthma within 6 months prior to Visit
- •A subject must not have current evidence of atelectasis (segmental or larger), bronchopulmonary dysplasia, chronic obstructive pulmonary disease, Or any evidence of concurrent respiratory disease other than asthma
- •A subject must not have any clinically significant, uncontrolled condition or disease state that, in the opinion of the investigator, would put the safety of the subject at risk through study participation or would confound the interpretation of the efficacy results if the condition/disease exacerbated during the study
- •Chronic stable hepatitis B or C are acceptable provided their screening alanine transaminase (ALT) is <2x upper limit of normal (ULN) and the y otherwise meet the entry criteria. Chronic co-infection with both hepatitis B and hepatitis C are not eligible
- •Clinical visual evidence of candidiasis at Visit 1
- •Use of any investigational drug within 30 days prior to Visit 1 or within five half-lives (t½), whichever is longer of the two.
- •Allergies to drug or milk protein: any adverse reaction, to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy or known or suspected sensitivity to the constituents of the NDPI, or history of severe milk protein allergy
- •Administration of medication that would significantly affect the course of asthma, or interact with study drug
- •Use of immunosuppressive medications during the study.
- •Use of potent CYP3A4 inhibitor within 4 weeks of Visit
- •A subject or his/her parent or legal guardian has any infirmity, disability, disease, or resides in a geographical location which seems likely, in the opinion of the Investigator, to impair compliance with any aspect of this study protocol, including visit schedule, and completion of the daily diaries.
- •Current smoker or has a smoking history of 10 pack-years (20 cigarettes/day for 10 years). A subject may not have used inhaled tobacco products within the past 3 months (i.e., cigarettes, cigars, or pipe tobacco).
- •If subject is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.
- •Subject previously randomized to treatment with FF/VI or FF in another Phase III study
- •Subjects working on night shift a week prior to Visit 1 or during the study period.
- •Adolescents who are wards of the state or government
研究组 & 干预措施
Arm1: Fluticasone Furoate/ Vilanterol 200/25 mcg
At Visit 3, eligible subjects for randomization will be stratified according to their baseline FEV1 performed at Visit 3 (<=65% or >65%) and randomized to one of the three treatment arms. Subjects in this arm will receive FF/ VI 200/25 mcg once daily in the evening for 84 days.
干预措施: Fluticasone Furoate/ Vilanterol 200/25 mcg (Drug)
Arm 2: Fluticasone Furoate/ Vilanterol 100/25 mcg
At Visit 3, eligible subjects for randomization will be stratified according to their baseline FEV1 performed at Visit 3 (<=65% or >65%) and randomized to one of the three treatment arms. Subjects in this arm will receive FF/ VI 100/25 mcg once daily in the evening for 84 days
干预措施: Fluticasone Furoate/ Vilanterol 100/25 mcg (Drug)
Arm 3: Fluticasone Furoate 100 mcg
At Visit 3, eligible subjects for randomization will be stratified according to their baseline FEV1 performed at Visit 3 (<=65% or >65%) and randomized to one of the three treatment arms. Subjects in this arm will receive FF 100 mcg once daily in the evening for 84 days
干预措施: Fluticasone Furoate 100 mcg (Drug)
结局指标
主要结局
Change From Baseline in Weighted Mean Forced Expiratory Volume in One Second (FEV1) Over 0 to 24 Hours Post-dose at the End of the 12-week Treatment Period
时间窗: Baseline and Week 12
Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 (within 30 minutes prior to dosing) and post-dose FEV1 measurements at 5, 15, and 30 minutes and at 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours on Day 84/Week 12. At each time point, the highest of three technically acceptable measurements was recorded. Change from Baseline was calculated as the weighted mean of the 24-hour serial FEV1 measures on Day 84/Week 12 minus the Baseline value. Baseline was the pre-dose FEV1 measurement value obtained at Visit 3. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline FEV1, region, sex, age, and treatment.
次要结局
- Change From Baseline in Clinic Visit Trough FEV1 at the End of the 12-week Treatment Period(Baseline and Week 12)
- Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods During the 12-week Treatment Period(Baseline and Weeks 1-12)
- Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 12-week Treatment Period(Baseline and Weeks 1-12)
- Change From Baseline in Daily Morning (AM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period(Baseline and Weeks 1-12)
- Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period(Baseline and Weeks 1-12)