A Six-Period Crossover, Dose-Ranging Study to Evaluate the Efficacy and Safety of Four Doses of FS Spiromax (Fluticasone Propionate/Salmeterol Xinafoate Inhalation Powder) Administered as Single Doses Compared With Single Doses of Fluticasone Propionate Spiromax and Open Label Advair Diskus in Adult and Adolescent Subjects With Persistent Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 10
- 主要终点
- Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12)
研究概览
简要总结
The primary objective of this study is to evaluate the dose response, efficacy, and safety of 4 different doses of salmeterol Spiromax (6.25, 12.5, 25, and 50 mcg) each combined with a fixed dose of fluticasone propionate (100 mcg) delivered as Fluticasone/Salmeterol Spiromax® Inhalation Powder (FS Spiromax) when administered as a single dose in subjects 12 years of age and older with persistent asthma.
详细描述
This was a multicenter, randomized, double-blind and open-label active-controlled, single-dose, 6 period crossover, dose-ranging study conducted in male and female subjects ages 12 years and older with persistent asthma.
Fluticasone propionate multidose dry powder inhaler (Fp MDPI) 50 mcg was provided (to replace the subject's current inhaled corticosteroid (ICS)) throughout the 14 day run-in period and each of the washout periods between treatments. Subjects were instructed to administer 2 inhalations of Fp MDPI 50 mcg (100 mcg total dose) twice daily during the run-in and washout periods. All other medications for the treatment of asthma were discontinued at or prior to the screening visit.
A short-acting β2-adrenergic agonist (SABA), salbuterol HFA, MDI, was provided (to replace the subject's current rescue medication) for symptomatic relief of asthma symptoms in each the run-in, treatment, and washout periods.
Treatment period lasted 5 weeks with a 5 to 7 day washout between each of the six single dose treatments:
- fluticasone propionate/salmeterol xinafoate multidose dry powder inhaler (FS MDPI) given in doses of 6.25, 12.5, 25, or 50 mcg of salmeterol xinafoate in blinded fashion.
- fluticasone propionate multidose dry powder inhaler (Fp MDPI) 100 mcg in blinded fashion
- ADVAIR DISKUS, 100/50 mcg in open-label fashion
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Written informed consent/assent
- •General good health
- •Diagnosis of asthma as defined by the National Institutes of Health (NIH)
- •A best FEV1 of 40%-85% of the predicted normal value during the screening visit (SV)
- •Subjects need to demonstrate a ≥ 15% reversibility of FEV1 within 30 minutes following 4 inhalations of albuterol inhalation aerosol (if required, spacers are permitted for reversibility testing) at the SV.
- •Other inclusion criteria apply
排除标准
- •History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation.
- •Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus, or middle ear that is not resolved within 2 weeks prior to the SV.
- •Any asthma exacerbation requiring oral corticosteroids within 3 months of the SV. A subject must not have had any hospitalization for asthma within 6 months prior to the SV.
- •Taking long-acting β-agonists within 2 weeks of the SV
- •Other exclusion criteria apply.
研究组 & 干预措施
FS MDPI 100/6.25 mcg
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.
干预措施: FS MDPI (Drug)
FS MDPI 100/6.25 mcg
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 6.25 mcg salmeterol xinafoate.
干预措施: Albuterol (Drug)
FS MDPI 100/12.5mcg
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.
干预措施: FS MDPI (Drug)
FS MDPI 100/12.5mcg
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 12.5 mcg salmeterol xinafoate.
干预措施: Albuterol (Drug)
FS MDPI 100/25
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
干预措施: FS MDPI (Drug)
FS MDPI 100/25
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 25 mcg salmeterol xinafoate.
干预措施: Albuterol (Drug)
FS MDPI 100/50
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.
干预措施: FS MDPI (Drug)
FS MDPI 100/50
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate.
干预措施: Albuterol (Drug)
Fp MDPI 100 mcg
Subjects inhaled a single dose of 100 mcg fluticasone propionate.
干预措施: Fp MDPI (Drug)
Fp MDPI 100 mcg
Subjects inhaled a single dose of 100 mcg fluticasone propionate.
干预措施: Albuterol (Drug)
Advair Diskus 100/50 mcg
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms.
干预措施: Advair Diskus (Drug)
Advair Diskus 100/50 mcg
Subjects inhaled a single dose of 100 mcg fluticasone propionate and 50 mcg salmeterol xinafoate. This arm is the only arm which is open-label because the inhaler device was different than the MDPI used in the other treatment arms.
干预措施: Albuterol (Drug)
结局指标
主要结局
Standardized Baseline-Adjusted Area Under the Curve For Forced Expiratory Volume In 1 Second Over 12 Hours Post-dose (FEV1 AUC0-12)
时间窗: Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 0.5, 1, 2, 3, 4, 5, 6, 9, 12 hours
Standardized baseline-adjusted FEV1 AUC0-12 was defined as the area under the curve for baseline-adjusted FEV1 measurements from the predose to 12 hours postdose time points using the trapezoidal rule based on actual (not scheduled) time of measurement and was standardized by dividing the actual time of last non-missing FEV1 measurement. Baseline-adjusted FEV1 was calculated as postdose FEV1 after subtracting period-specific baseline FEV1. The period-specific baseline FEV1 was measured at predose within 5 minutes of AM dose administration at each treatment visit. If that value was missing, then FEV1 measured at 30 minutes predose was used as the period-specific baseline.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of Salmeterol(Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose)
- Patients With Treatment-Emergent Adverse Experiences (TEAE) During the Treatment Period(Day 1 up to Day 35)
- Change From Baseline at 12 Hours Post-Dose in Forced Expiratory Volume in One Second (FEV1) By Treatment(Pre-dose: 30 minutes prior, within 5 minutes of dose. Post-dose: 12 hours)
- Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t) of Salmeterol(Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose)
- Time of Maximum Observed Plasma Concentration (Tmax) of Salmeterol(Predose (0), and at 5, 10, 15 and 30 minutes, 1, 1.5, 2, 3, 4, 8, and 12 hours postdose)