A RANDOMIZED, DOUBLE BLIND, MULTIPLE DOSING (14 DAYS), PLACEBO-CONTROLLED, INCOMPLETE BLOCK CROSSOVER, MULTI CENTER STUDY TO ASSESS EFFICACY AND SAFETY OF THREE DOSE LEVELS OF AZD7594, GIVEN ONCE DAILY BY INHALATION, IN PATIENTS WITH MILD TO MODERATE ASTHMA
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15
研究概览
简要总结
This study will be a randomised, double-blind, multiple dose (14 days), placebo-controlled, multi-center study to assess efficacy and safety of three dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.
详细描述
This is a randomized, double-blind, multiple dosing (14 ± 1 days), placebo-controlled, incomplete block crossover, multi-center study to assess efficacy and safety of 3 dose levels of AZD7594, given once daily by inhalation, in patients with mild to moderate asthma.
This multi-center study will be conducted at multiple sites in Europe. It is planned that approximately 48 patients with mild to moderate asthma will be randomized into the study
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body mass index of 18 to 35 kg/m2
- •Men and women 18 to 75 years of age, inclusive
- •Patients need to be non-smokers or ex-smokers (quit ≥ 6 months before the Visit 1) with total smoking history of < 10 pack years
- •Documented clinical diagnosis of asthma for ≥ 6 months before the Visit 1
- •Patients on low-dose inhaled corticosteroids (ICS) (equivalent of budesonide ≤ 400 μg per day) or low-dose ICS/long-acting β-2 agonist (LABA), or not on any inhaled steroids, or patients on montelukast
- •Patients should be controlled on low dose budesonide during the first 14 ±2 days of Run-in Part 1, i.e., they need to have ACQ-5 of ≤ 1.5 at Visit
- •Prebronchodilator FEV1 at Visit 3 should be between 40% and 90% of predicted (mean of 2 predose measurements taken 30 minutes apart).
- •All patients need to have FeNO concentrations of ≥ 25 parts per billion at Visit 3
- •Demonstrate the ability to use the study inhalation device properly
- •Women must be of nonchildbearing potential defined as meeting 1 of the following criteria:
- •Permanently or surgically sterilized, including hysterectomy and/or bilateral oophorectomy and/or bilateral salpingectomy
- •Postmenopausal; aged ≤ 50 years and have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range
- •Postmenopausal; aged > 50 years and have been amenorrheic for 12 months or more, following cessation of all exogenous hormonal treatments
- •Male patients should be willing to use a condom to prevent pregnancy and exposure of a female partner to AZD7594 and should refrain from donating sperm or fathering a child from the first day of dosing until 3 months after the last dose of IMP.
排除标准
- •Known or suspected hypersensitivity to the IMPs or excipients, including lactose
- •Systemic steroid use in the 6 weeks before Visit 1
- •Any active disease other than asthma
- •Patients on medium to high-dose ICS (equivalent of budesonide > 400 μg per day) or on inhaled anticholinergic combination within the 6 weeks prior to Visit 1
- •Compliance with the eDiary of at least 80% of the days is expected in both Run-in and Treatment Periods. Patients with < 80% eDiary compliance during Run-in Periods would not be randomized
- •Treatment with biologicals such as monoclonal antibodies or chimeric biomolecules including omalizumab within 6 months or 5 half-lives before Visit 1, whichever is longer
- •History or clinical suspicion of any clinically relevant disease or disorder which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results or the patient's ability to participate in the study, or any other safety concerns in the opinion of the Investigator
- •ACQ-5 ≥ 3 at any time between Visits 1 and 3
- •Any contraindication against the use of vagolytic or sympathomimetic drugs as judged by the Investigator.
- •Patients with hepatitis B surface antigen, hepatitis C virus antibody or human immunodeficiency virus (HIV)
- •Donation of blood (≥ 450 mL) within 3 months or donation of plasma within 14 days before Visit 1
- •Pregnant woman or a nursing mother
- •Suspicion of Gilbert's syndrome
- •Vulnerable persons (e.g., persons kept in detention)
- •ACQ-5 of ≥ 3 or daily rescue use of ≥ 12 puffs for ≥ 3 consecutive days during the enrollment period
- •Hypersensitivity to the active substance or to any of the excipients of the Run-in medication (i.e., budesonide)
研究组 & 干预措施
Sequence 5
58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: 800 μg AZD7594 once daily (Drug)
Sequence 5
58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: 58 µg AZD7594 once daily (Drug)
Sequence 5
58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: Placebo once daily (Drug)
Sequence 7
250 µg AZD7594 once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: 250 µg AZD7594 once daily (Drug)
Sequence 7
250 µg AZD7594 once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: 58 µg AZD7594 once daily (Drug)
Sequence 7
250 µg AZD7594 once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: Placebo once daily (Drug)
Sequence 9
800 µg AZD7594 once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: 800 μg AZD7594 once daily (Drug)
Sequence 6
250 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3
干预措施: Placebo once daily (Drug)
Sequence 8
800 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3
干预措施: 800 μg AZD7594 once daily (Drug)
Sequence 8
800 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3
干预措施: 250 µg AZD7594 once daily (Drug)
Sequence 8
800 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3
干预措施: Placebo once daily (Drug)
Sequence 9
800 µg AZD7594 once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: 250 µg AZD7594 once daily (Drug)
Sequence 9
800 µg AZD7594 once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: Placebo once daily (Drug)
Sequence 1
Placebo once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3
干预措施: 250 µg AZD7594 once daily (Drug)
Sequence 4
58 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3
干预措施: 800 μg AZD7594 once daily (Drug)
Sequence 9
800 µg AZD7594 once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: Salbutamol (Drug)
Sequence 7
250 µg AZD7594 once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: Salbutamol (Drug)
Sequence 8
800 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3
干预措施: Salbutamol (Drug)
Sequence 4
58 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3
干预措施: Salbutamol (Drug)
Sequence 3
Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3
干预措施: Salbutamol (Drug)
Sequence 1
Placebo once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3
干预措施: Salbutamol (Drug)
Sequence 1
Placebo once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3
干预措施: 58 µg AZD7594 once daily (Drug)
Sequence 1
Placebo once daily for 14 days in Period 1, 58 µg AZD7594 once daily for 14 days in Period 2 and 250 µg AZD7594 once daily for 14 days in Period 3
干预措施: Placebo once daily (Drug)
Sequence 2
Placebo once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3
干预措施: 800 μg AZD7594 once daily (Drug)
Sequence 2
Placebo once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3
干预措施: 250 µg AZD7594 once daily (Drug)
Sequence 2
Placebo once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3
干预措施: Placebo once daily (Drug)
Sequence 3
Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3
干预措施: 800 μg AZD7594 once daily (Drug)
Sequence 3
Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3
干预措施: 58 µg AZD7594 once daily (Drug)
Sequence 3
Placebo once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3
干预措施: Placebo once daily (Drug)
Sequence 4
58 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3
干预措施: 58 µg AZD7594 once daily (Drug)
Sequence 4
58 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3
干预措施: Placebo once daily (Drug)
Sequence 6
250 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3
干预措施: 250 µg AZD7594 once daily (Drug)
Sequence 6
250 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3
干预措施: 58 µg AZD7594 once daily (Drug)
Sequence 2
Placebo once daily for 14 days in Period 1, 250 µg AZD7594 once daily for 14 days in Period 2 and 800 µg AZD7594 once daily for 14 days in Period 3
干预措施: Salbutamol (Drug)
Sequence 6
250 µg AZD7594 once daily for 14 days in Period 1, Placebo once daily for 14 days in Period 2 and 58 µg AZD7594 once daily for 14 days in Period 3
干预措施: Salbutamol (Drug)
Sequence 5
58 µg AZD7594 once daily for 14 days in Period 1, 800 µg AZD7594 once daily for 14 days in Period 2 and Placebo once daily for 14 days in Period 3
干预措施: Salbutamol (Drug)
结局指标
主要结局
Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 15
时间窗: On Day 1 (pre-dose) and on Day 15 in each period
Comparison of the efficacy of AZD7594 in terms of change from baseline in morning trough forced expiratory volume in 1 second (FEV1) on Day 15 (defined as the average of the values at 23:00 and 23:30 hours after last dose of investigational medicinal product \[IMP\] on Day 14) with placebo
次要结局
- Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 8(On Day 1 (pre-dose) and on Day 8 in each period)
- Efficacy of AZD7594 by Assessment of the Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) on Day 15(On Day 1 (pre-dose) and on Day 15 in each period)
- Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) on Day 8(On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period)
- Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 15(On Day 1 (pre-dose) and on Day 15 (pre-dose) in each period)
- Efficacy of AZD7594 by Assessment of the Change From Baseline in Trough Forced Vital Capacity (FVC) on Day 8(On Day 1 (pre-dose) and on Day 8 (pre-dose) in each period)
- Efficacy of AZD7594 by Assessment of the Change From Baseline in Morning Peak Expiratory Flow (mPEF) Before Administration Over the Treatment Period(Every morning at pre-dose from Day 1 to Day 15)
- Efficacy of AZD7594 by Assessment of the Change From Baseline in Evening Peak Expiratory Flow (ePEF) Before Administration Over the Treatment Period(Every evening from Day 1 to Day 14 in each period)
- Efficacy of AZD7594 by Assessment of the Change From Baseline in Average Daily Use of Rescue Salbutamol Over the Treatment Period(Every day from Day 1 to Day 15 (from evening of Day 1 to morning of Day 15))
- Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 15 in Asthma Control Questionnaire-5(At baseline and on Day 15 in each period)
- Efficacy of AZD7594 by Assessment of the Change From Baseline to Day 8 in Asthma Control Questionnaire-5(At baseline and on Day 8 in each period)
- Efficacy of AZD7594 by Assessment of Night-time Awakenings(At baseline and from Day 2 to Day 15 in each period)
- Efficacy of AZD7594 by Assessment of Daily Symptom Score(At baseline and from Day 1 to Day 14 in each period)
- Efficacy of AZD7594 by Assessment of Asthma Control Days(At baseline and from Day 1 to Day 14 post-dose in each period)
- Number of Participants With Adverse Events(From Screening to Follow-up (these two examinations are up to 165 days apart))
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Cmax of AZD7594(On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose))
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of AUC(0-4) of AZD7594(On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose))
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax,ss of AZD7594(On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose))
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24) of AZD7594(On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose))
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-last) of AZD7594(On Day 1 and Day 14 in each period (in participants with intensive pharmacokinetic assessments, on Day 1 at pre-dose and 15 and 30 minutes, and 1, 2 and 4 h post-dose, on Day 14 at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose))
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 by Assessment of Tmax of AZD7594(On Day 1 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, and 4 h post-dose))
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Tmax,ss of AZD7594(On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose))
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cavg,ss of AZD7594(On Day 14 in each period (in participants with intensive pharmacokinetic assessments, at pre-dose and 15 and 30 minutes, and 1, 2, 4, 8, 12, 16 and 24 h post-dose))
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmax/D of AZD7594(On Day 1 in each period)
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of AUC(0-24)/D of AZD7594(On Day 14 in each period)
- Rate and Extent of Absorption of Three Dose Levels of AZD7594 Following Multiple Dose Administration by Assessment of Cmin of AZD7594(On Day 14 at pre-dose in each period)