A 12-week, Randomized, Double-blind, Placebo-controlled, Multicenter, Parallel Group, Phase III Study Evaluating the Efficacy and Safety of PT027 Compared to PT008 and PT007 Administered QID in Adults and Children 4 Years of Age or Older With Asthma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,001
- 试验地点
- 1
- 主要终点
- Change From Baseline in Trough FEV1
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, multicenter, parallel group study to compare 2 dose levels of budesonide/albuterol BDA MDI (PT027) to its components budesonide BD MDI (PT008) and albuterol AS MDI (PT007) on improvement in lung function and asthma symptoms after 12 weeks of treatment in adult, adolescent, and child subjects with symptomatic asthma currently being treated with a short/rapid-acting β2-adrenoreceptor agonist (SABA) as needed alone or with low-dose inhaled corticosteroid (ICS) maintenance therapy plus SABA as needed.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 4 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male aged ≥4 years at the time of informed consent
- •Physician diagnosis of asthma with a documented history of the last 6 months
- •Receiving 1 of the following inhaled asthma medications with stable dosing for at least 30 days prior to Visit 1:
- •Only short/rapid-acting β2-adrenoreceptor agonist (SABA) used as needed
- •Stable low-dose inhaled corticosteroid in addition to as-needed use of SABA
- •Pre-bronchodilator FEV1 of ≥50 to <85% predicted normal value for adults (≥18 years of age) and ≥50% predicted normal value for subjects aged 4 to 17 years after withholding SABA ≥6 hours at Visit
- •Demonstrate reversibility of airflow limitation defined as a ≥15% increase in FEV1 relative to baseline after administration of Sponsor-provided SABA (Ventolin) at either Visit 1 or Visit 1a.
- •Demonstrate acceptable spirometry performance acceptability/repeatability criteria
- •Taken Ventolin on ≥2 days out of 7 days prior to Visit 2
- •Demonstrate acceptable metered dose inhaler (MDI) administration technique as assessed by the investigator.
- •Able to perform acceptable and reproducible peak expiratory flow measurements as assessed by the investigator
排除标准
- •Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or bronchopulmonary dysplasia)
- •Systemic corticosteroids (SCS) use (any dose and any indication) within 3 months before Visit 1
- •Chronic (≥3 weeks) use of SCS within 6 months prior to Visit 1
- •Received any marketed (eg, omalizumab, mepolizumab, reslizumab, benralizumab) or investigational biologic within 3 months or 5 half-lives before Visit 1, whichever is longer, or any other prohibited medication
- •Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking <6 months before Visit 1 (including all forms of tobacco, e-cigarettes [vaping], and marijuana)
- •Life-threatening asthma defined as any history of significant asthma episode(s) requiring admission to an intensive care unit, intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) within 5 years of Visit 1
- •Completed treatment for lower respiratory infection within 6 weeks prior to Visit 1
- •Upper respiratory infection involving antibiotic treatment not resolved within 7 days prior to Visit 1
- •Hospitalizations due to asthma within 6 months prior to Visit 1
- •Have taken ≥12 actuations per day of Sponsor-provided Ventolin during the run-in period prior to Visit 2 according to the below criteria:
- •≥2 days out of 14 days of run-in
- •≥3 days out of 15 to 21 days of run-in
- •≥4 days out of 22 or more days of run-in
- •Unable to comply with study procedures including non-compliance with diary completion (ie, <70% subject completion of diary assessments in the last 7 days preceding Visit 2 or 4-times daily dosing, <80% compliance during the placebo run-in period).
- •Historical or current evidence of a clinically significant disease
- •Cancer not in complete remission for at least 5 years before Visit 1
- •Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1
- •History of psychiatric disease, intellectual deficiency, poor motivation, or other conditions if their magnitude is limiting informed consent validity
- •Significant abuse of alcohol or drugs, in the opinion of the investigator
研究组 & 干预措施
BDA MDI (PT027) 160/180 μg
Budesonide/Albuterol sulfate BDA MDI (PT027) high dose
干预措施: Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 160/180 μg (high dose) (Combination Product)
BDA MDI (PT027) 80/180 μg
Budesonide/Albuterol sulfate BDA MDI (PT027) low dose
干预措施: Budesonide/albuterol sulfate metered dose inhaler / BDA MDI 80/180 μg (low dose) (Combination Product)
BD MDI (PT008) 160 µg
Budesonide BD MDI (PT008)
干预措施: Budesonide metered dose inhaler / BD MDI 160 µg (Drug)
AS MDI (PT007) 180 µg
Albuterol sulfate AS MDI (PT007)
干预措施: Albuterol sulfate metered dose inhaler / AS MDI 180 μg (Drug)
Placebo MDI
Placebo MDI
干预措施: Placebo metered-dose inhaler / Placebo MDI (Other)
结局指标
主要结局
Change From Baseline in Trough FEV1
时间窗: Baseline and 12 weeks
Trough FEV1 is calculated at each clinic visit as the average of the 30- and 60-minute pre-dose FEV1 measurements. Baseline FEV1 is defined as the average of the 30- and 60-minute pre-dose measures collected on the day of randomization.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Area Under the Concentration Curve From 0 to 6 Hours (AUC0-6 Hours) Over 12 Weeks
时间窗: Baseline and 12 weeks
Lung function will be measured by spirometry. Baseline FEV1 will be taken as the average of the 60- and 30-minute pre-dose spirometry measures on or before randomization. Starting with the first study drug dose at Week 0 and then at Week 12, spirometry assessments will be completed at 60 and 30 minutes before the morning dose and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes after dosing. FEV1 AUC0-6 hours will be calculated for changes from baseline (randomization visit) using the trapezoidal rule and will be normalized by dividing by the time (in hours) from dosing to the last measurement included (typically 6 hours).
次要结局
- Number of Participants With a Clinically Meaningful Difference on the Asthma Control Questionnaire 7-item Version (ACQ-7) at Week 12.(Baseline and 12 weeks)
- Change From Baseline in Trough FEV1 at Week 1.(Baseline and 1 week)
- Duration of 15% Increase in FEV1 Over the Pre-treatment Value on Day 1(Onset up to about 40 minutes post-treatment, with duration lasting up to the last assessment of a nominal 6 hour serial spirometry profile (Day 1).)
- Time to 15% Increase in FEV1 Over the Pre-treatment Value on Day 1(From first dose (first inhalation of randomized treatment) up to about 40 minutes post-dose (Day 1).)