Phase I Study to Compare the Pharmacokinetics of Budesonide and Formoterol Delivered With Symbicort Aerosphere® and Symbicort® pMDI in Children 4 to Less Than 12 Years of Age With Asthma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 16
- 试验地点
- 6
- 主要终点
- Maximum observed plasma concentration (Cmax)
研究概览
简要总结
The purpose of this study is to assess the pharmacokinetics (PK) and safety of symbicort aerosphere and symbicort pressurized metered dose inhaler (pMDI) in participants with asthma aged 4 to less than 12 years.
详细描述
This is a phase I single-dose, 2-period cross-over, multicenter study in which the participants will be randomized 1:1 to one of two treatment sequences - AB or BA. In the first study period, participants will receive a single dose of either -
- Treatment A: Symbicort Aerosphere budesonide/formoterol fumarate × 2 puffs (test formulation)
- Treatment B: Symbicort pMDI budesonide/formoterol fumarate × 2 puffs (reference formulation)
After a washout period of at least 28 days and no longer than 42 days, participants who first received Treatment A will receive a single dose of Treatment B, and participants who first received Treatment B will receive a single dose of Treatment A in the study period 2.
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
- None
入排标准
- 年龄范围
- 4 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who have clinician-diagnosed asthma for at least 3 months.
- •Body mass index ≤ 95 percentile for age and body weight of at least 15 kg or higher.
- •Be on a stable dose of one of the following asthma treatments for at least 4 weeks prior to screening (Visit 1):
- •Short-acting β2 agonist (SABA) used as rescue/reliever medication (as needed) only.
- •Low- or medium-dose inhaled corticosteroids (ICS).
- •Leukotriene receptor antagonist (LTRA).
- •Low-dose ICS/long-acting β2-agonist (LABA).
- •Medium-dose ICS/LABA.
- •Female participants who experience menarche must have a negative urine pregnancy test at screening.
排除标准
- •Current evidence of pneumonia, pneumothorax, atelectasis, pulmonary fibrotic disease, allergic bronchopulmonary aspergillosis, cystic fibrosis, bronchopulmonary dysplasia, or other severe respiratory abnormalities other than asthma.
- •History of life-threatening asthma defined as any asthma episode associated with loss of consciousness, intubation or admission to an intensive care unit.
- •History of severe asthma exacerbation within 8 weeks of Visit
- •Inability to change from any budesonide therapy to another suitable corticosteroid.
- •Participants with a known hypersensitivity to budesonide and/or formoterol fumarate or any of the excipients of the product.
- •Not be able to refrain from consuming alcohol and smoking (including electronic cigarettes, vaping, and marijuana) from the time of screening until after the safety follow-up visit.
- •Unstable asthma.
- •Received regular maintenance treatment with prohibited anti-inflammatory or long-acting bronchodilator asthma medication.
- •Evidence of active liver disease.
- •Prolonged QT interval corrected for heart rate using Fridericia's correction (QTcF).
研究组 & 干预措施
Sequence AB
In study period 1, participants will receive a single dose of treatment A (test formulation) and in study period 2, participants will receive a single dose of treatment B (reference formulation).
干预措施: Budesonide/formoterol fumarate Aerosphere (Combination Product)
Sequence AB
In study period 1, participants will receive a single dose of treatment A (test formulation) and in study period 2, participants will receive a single dose of treatment B (reference formulation).
干预措施: Budesonide/formoterol fumarate pMDI (Combination Product)
Sequence BA
In study period 1, participants will receive a single dose of treatment B (reference formulation) and in study period 2, participants will receive a single dose of treatment A (test formulation).
干预措施: Budesonide/formoterol fumarate Aerosphere (Combination Product)
Sequence BA
In study period 1, participants will receive a single dose of treatment B (reference formulation) and in study period 2, participants will receive a single dose of treatment A (test formulation).
干预措施: Budesonide/formoterol fumarate pMDI (Combination Product)
结局指标
主要结局
Maximum observed plasma concentration (Cmax)
时间窗: Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose
To determine and compare the systemic availability (Cmax) of budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma.
Area under the plasma concentration-time curve from time 0 to 6 hours postdose (AUC0-6)
时间窗: Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours and 6 hours postdose
To determine and compare the systemic availability (AUC0-6) of budesonide and formoterol after single doses of Symbicort Aerosphere and Symbicort pMDI in participants 4 to less than 12 years of age with asthma.
次要结局
- Time to reach peak or maximum observed concentration or response following drug administration (tmax)(Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose)
- Terminal elimination rate constant (λz)(Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose)
- Terminal elimination half-life (t½λz)(Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose)
- Area under plasma concentration-time curve from time 0 to infinity (AUCinf)(Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose)
- Mean residence time (MRT)(Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose)
- Apparent total body clearance (CL/F)(Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose)
- Apparent volume of distribution based on the terminal phase (Vz/F)(Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose)
- Number of participants with adverse events(From Screening (Day -14 to Day -1) to Follow-up telephone call (approximately 7 weeks))
- Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)(Participants < 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 3 hours, and 6 hours postdose; Participants ≥ 30 kg: Predose, 5 minutes, 10 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, and 8 hours postdose)