A Double Blind, Double Dummy, Randomized, Two Way Cross-over Study to Compare the Effects of Z7200 and Symbicort® Turbohaler on Functional Respiratory Imaging Parameters in Asthmatic Patients.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Zambon SpA
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Total Airway Volume (iVaw)
研究概览
简要总结
Primary objective:
The primary objective of this study is to evaluate the effect of the products under investigation on functional respiratory imaging parameters and evaluate the particle deposition with Computational fluid dynamics (CFD).
Secondary Objectives:
The secondary objectives of this study were to assess the effect of test product and reference product on:
- lung function (spirometry and body plethysmography),
- exercise capacity (6-Minute Walking Test [6MWT] or equivalent method to measure exercise tolerance),
- dyspnea (Borg Category [C] Ratio [R] 10 [Borg CR10] scale and Visual Analogue Scale [VAS] dyspnea).
Furthermore, the safety of the test product and reference product was evaluated through monitoring of AEs throughout the study.
详细描述
This study is conducted as a randomized, double blind, double dummy two-period crossover study in stable asthma patients treated in accordance with the Global Initiative for Asthma (GINA) guidelines.
On the first dosing day (Period 1, Visit 2), asthma stability was assessed based on review of pharmacologic treatment monitoring and FEV1 change from the previous visit. Patients were then randomized and allocated to one of two treatment sequences (i.e. test/reference or reference/test). Randomization codes were assigned strictly sequentially as patients became eligible for randomization. Patients received a single dose consisting of two inhalations of either the test product or the reference product, according to the assigned treatment sequence, in the presence of the Investigator or authorized site personnel. In addition, patients received two inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding. All patients followed the same sequence of device inhalation, i.e. Symbicort or placebo Turbohaler first and Z7200 or placebo RS-01 inhaler second.
On the second dosing day (Period 2, Visit 3), patients underwent the same asthma stability check and procedures as in Visit 2. Patients received a single dose consisting of two inhalations of the other treatment (reference in case test product was administered at Visit 2 and vice versa) plus two inhalations with matching placebo to the alternate treatment.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Male or female patient ≥ 18 years old.
- •Written informed consent obtained.
- •Patient with a documented diagnosis of asthma according to the Global Initiative for Asthma (GINA) guidelines
- •Patient with a co-operative attitude and ability to correctly use the DPI.
- •Female patient of childbearing potential who confirm that a reliable method of contraception was used at least 14 days before visit 1 and will continue to use a reliable method of contraception during the study, or post-menopausal women (at least 12 months of amenorrhea)
- •Patient must be stable and treated in accordance with the GINA guidelines.
- •Patient must be a non-smoker or ex-smoker who have stopped smoking at least 1 month prior to visit 1 and has a smoking history of < 10 pack years.
- •Patient must be able to understand and complete the protocol requirements, instructions, questionnaires and protocol-stated restrictions.
排除标准
- •Pregnant or lactating female.
- •Unstable patient who developed an asthma exacerbation in the 4 weeks before screening.
- •Patient with upper or lower airways infection in the 4 weeks before screening.
- •Patient unable to perform pulmonary function testing.
- •Patients unable to withdraw fixed combination or long acting bronchodilator inhalation products
- •Patient with an uncontrolled disease or any condition that might, in the judgement of the investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study.
- •Patient with active lung cancer or any other chronic disease with poor prognosis and /or affecting patient status.
- •Patient with allergy, sensitivity or intolerance to study drugs and/ or study drug formulation ingredients.
- •Patient unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study.
- •Patient who received systemic corticosteroids within the last 4 weeks prior to visit
- •Patient who received any investigational new drug within the last 4 weeks prior to visit 1 and is participating in any clinical trial.
- •Patient with a history of alcohol or substance abuse that in the opinion of the investigator may be of clinical significance
- •Patient with diagnosis of Chronic Obstructive Pulmonary Disease (COPD).
- •Patients who has a lactose intolerance or history of allergy to milk proteins.
- •Patients treated with medications or herbal medicines that are strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, indinavir, nelfinavir, saquinavir, atazanavir, ketoconazole, itraconazole, voriconazole, fluconazole, cyclosporine, mibefradil, nefazodone, clarithromycin, telithromycin, troleandromycin, norfloxacin, ciprofloxacin) or inducers (e.g. phenobarbital, phenytoin, barbiturates, carbamazepine, oxcarbazepine, rifabutin, rifampin, St John's wort) within 2 weeks prior to Screening Visit and during the study.
研究组 & 干预措施
Z7200 - Symbicort® Turbohaler
The patients randomized to this sequence were to receive a single dose consisting of 2 inhalations of the test product (Z7200) on the first dosing day (Period 1, Visit 2), then, after a wash out period of at least 3 days but no more of 31 days, a single dose consisting of 2 inhalations of the reference treatment (Symbicort® Turbohaler) on the second dosing day (Period 2, Visit 3).
Patients were also to receive 2 inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding.
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
干预措施: Z7200 (Drug)
Z7200 - Symbicort® Turbohaler
The patients randomized to this sequence were to receive a single dose consisting of 2 inhalations of the test product (Z7200) on the first dosing day (Period 1, Visit 2), then, after a wash out period of at least 3 days but no more of 31 days, a single dose consisting of 2 inhalations of the reference treatment (Symbicort® Turbohaler) on the second dosing day (Period 2, Visit 3).
Patients were also to receive 2 inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding.
Z7200 is contained in single dose capsules (HPMC) and it is administered through a single dose dry powder inhaler (DPI), that is structurally correspondent to Aerolizer/Cyclohaler device.
Strength: Each delivered dose contains budesonide 80 mcg/inhalation and formoterol fumarate dihydrate 2.25 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 160 mcg/4.5 mcg) to be administered only with the inhaler device (RS-01) provided.
干预措施: Symbicort® Turbohaler® (Drug)
Symbicort® Turbohaler - Z7200
The patients randomized to this sequence were to receive a single dose consisting of 2 inhalations of the reference treatment (Symbicort® Turbohaler) on the first dosing day (Period 1, Visit 2), then, after a wash out period of at least 3 days but no more of 31 days, a single dose consisting of 2 inhalations of the test product (Z7200) on the second dosing day (Period 2, Visit 3).
Patients were also to receive 2 inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding.
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 320 mcg/9 mcg).
干预措施: Z7200 (Drug)
Symbicort® Turbohaler - Z7200
The patients randomized to this sequence were to receive a single dose consisting of 2 inhalations of the reference treatment (Symbicort® Turbohaler) on the first dosing day (Period 1, Visit 2), then, after a wash out period of at least 3 days but no more of 31 days, a single dose consisting of 2 inhalations of the test product (Z7200) on the second dosing day (Period 2, Visit 3).
Patients were also to receive 2 inhalations with matching placebo to the alternate treatment as a dummy inhaler to achieve double-blinding.
Symbicort® Turbohaler® inhalation powder; AstraZeneca UK Limited. Budesonide and formoterol fumarate dihydrate concentration Strength: Each delivered dose contains budesonide 160 mcg/inhalation and formoterol fumarate dihydrate 4.5 mcg/inhalation; two inhalations (i.e. total dose budesonide/formoterol is 320 mcg/9 mcg).
干预措施: Symbicort® Turbohaler® (Drug)
结局指标
主要结局
Total Airway Volume (iVaw)
时间窗: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
The Total Airway Volume is the amount of air that can be inhaled or exhaled during one respiratory cycle. This depicts the functions of the respiratory centers, respiratory muscles and the mechanics of the lung and chest wall. The higher the volume, the better the outcome.
Total Airway Resistance (iRaw)
时间窗: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
The Total Airway Resistance refers to degree of resistance to the flow of air through the respiratory tract during inspiration and expiration. The degree of resistance depends on many things, particularly the diameter of the airway and whether flow is laminar or turbulent. The higher the resistance, the worse the outcome. In healthy men and women values range between 0.22 to 0.25 kPa/l.
Number of Deposited Particles Per Pre-defined Airway Section
时间窗: Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.
To evaluate the particle deposition in the lungs, the Computational Fluid Dynamic (CFD) was used. With CFD, based on the computed tomography (CT) derived geometries of the airways, it is possible to measure the resistance of all airways or subdivisions such as the smaller airways starting from the 3rd bifurcation onwards. The three-dimensional (3D) reconstruction in this CT-based imaging technique allows for an accurate measurement of local volume changes in the central and peripheral airways after the administration of the product. The increased sensitivity of this technique makes it possible to detect changes in airway caliber in early stages of asthma.
次要结局
- Spirometry - MEF25(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Spirometry - FEV1(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Inhalation Profile(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- 6MWT(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Borg CR10 Scale (Pre-6MWT)(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Borg CR10 Scale (Post-6MWT)(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- VAS (Post-6MWT)(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Spirometry - PEF(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Spirometry - MEF50(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Body Plethysmography - TLC(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Spirometry - FVC(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Spirometry - FEV1/FVC Ratio(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Body Plethysmography - FRC(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Body Plethysmography - Raw(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- VAS (Pre-6MWT)(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)
- Body Plethysmography - SRaw(Predose and postdose at the dosing visit V2 [ 7 (minimum) to 31 (maximum) days after Screening] or V3 [ 3 (minimum) to 31(maximum) days after visit 2] up to a maximun of Day 83.)