A Phase I, Randomized, Partial Double-blind, Single-dose, 3-Way Cross-over Study to Assess the Total Systemic Exposure of Budesonide, Glycopyrronium, and Formoterol for BGF MDI HFO Compared With BGF MDI HFA Using an AeroChamber Plus Flow-Vu Spacer and to Compare the Total Systemic Exposure of BGF MDI HFO With a Spacer to BGF MDI HFO Without a Spacer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-curve from Zero to the Last Quantifiable Concentration (AUClast) of BGF MDI
研究概览
简要总结
This study aims to assess the effect on total systemic exposure and to characterize exposure BGF MDI HFO with a spacer compared to without a spacer; also, to demonstrate that total systemic exposure of BGF when administered as MDI HFO with a spacer is not greater than BGF MDI HFA with a spacer.
详细描述
This is a Phase I, randomized, partial double-blind, single dose, three way cross-over study to assess the effect of total systemic exposure of BGF when administered as BGF MDI HFO compared with BGF MDI HFA Using an AeroChamber Plus Flow-Vu Spacer and to compare the Total Systemic Exposure of BGF MDI HFO with a Spacer to BGF MDI HFO without a Spacer in healthy participants (male or female).
The study will comprise of:
- A Screening Period of up to 27 days prior to first dosing.
- Three treatment periods: participants will be resident at the Clinical Unit from Day -1 until 24 hours after dosing with the final treatment, with a washout period of 3 to 7 days between each dose administration.
- Follow-up: a final Follow-up Phone Call within 5 to 7 days after the last administration of BGF MDI in Treatment Period 3.
Participants will receive all 3 treatments as a single dose (4 inhalations) (Treatment A [BGF MDI HFA with AeroChamber Plus Flow-Vu spacer - reference formulation], Treatment B [BGF MDI HFO with AeroChamber Plus Flow-Vu spacer - test formulation], and Treatment C [BGF MDI HFO without spacer]) (1 treatment per treatment period) in one of 6 possible treatment sequences; ABC, ACB, BAC, BCA, CAB, or CBA.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Females must have a negative pregnancy test at screening and on admission to the Clinical Unit, must not be lactating, confirmed at screening.
- •Women of childbearing potential who are sexually active with a non-sterilized male partner, must use 1 highly effective form of birth control from enrolment throughout the study and until at least 14 days after last dose of IMP. Women should be stable on their chosen method of birth control for at least 1 month from enrolment.
- •Have a body mass index between 18 and 30 kg/m2 inclusive and weigh at least 50 kg.
- •Have a Forced expiratory volume in the first second (FEV1) ≥ 80% of the predicted normal value and an FEV1/forced vital capacity> 70% regarding age, height, and ethnicity at screening.
- •Demonstrate basic understanding of how to use an MDI device with and without a spacer after receiving training.
- •Participants should be fully/sufficiently vaccinated as per local definitions against SARS-CoV-2 (in combination with confirmed past infections with SARS-CoV-2).
排除标准
- •History or current evidence of any clinically significant disease or disorder, including endocrinological diseases, such as thyrotoxicosis, which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the results through participation in the study.
- •Participants who have previously received BGF MDI HFO.
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the investigator, or history of hypersensitivity to drugs with a similar chemical structure or class to BGF or to its excipients, such as norflurane.
- •History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
- •History of narrow angle glaucoma or change in vision that may be relevant.
- •History of symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, which in the opinion of the investigator, is clinically significant.
- •Unresectable cancer that has not been in complete remission for at least 5 years.
- •Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, at screening as judged by the investigator.
- •Any clinically significant abnormal findings in physical examination or vital signs at screening, as judged by the investigator.
- •Any clinically significant abnormalities on 12-lead ECG at screening, as judged by the investigator.
- •Any positive result on screening for serum hepatitis B surface antigen or anti-hepatitis B core antibody, indicative of hepatitis B, hepatitis C antibody, or human immunodeficiency virus.
- •Positive reverse transcription polymerase chain reaction test for SARS-CoV-2 prior to randomization.
- •Participant has clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, dyspnea, sore throat, fatigue, new smell or taste disorder or confirmed infection by appropriate laboratory test within the last 4 weeks prior to screening or on admission.
- •Participant who had severe course of COVID-19 (ie, hospitalization, extracorporeal membrane oxygenation, or mechanically ventilated).
- •Recent (within 14 days prior to admission to the Clinical Unit) exposure to someone who has COVID-19 symptoms or tested positive for SARS-CoV-
- •History of any respiratory disorders such as asthma, COPD, or idiopathic pulmonary fibrosis.
- •Known or suspected history of drug abuse.
- •Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 3 months prior to screening.
- •Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- •Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during the 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
- •Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
- •Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate).
研究组 & 干预措施
BGF MDI HFA
Budesonide/Glycoperronium/formoterol fumarate pressurised inhalation suspension 160/7.2/4.8 μg per actuation, hydrofluoroalkane with AeroChamber Plus Flow-Vu spacer-reference formulation
干预措施: AeroChamber Plus Flow-Vu spacer (Device)
BGF MDI HFO with spacer
Budesonide/Glycoperronium/formoterol fumarate pressurised inhalation suspension 160/7.2/4.8 μg per actuation, hydrofluoroolefin with AeroChamber Plus Flow-Vu spacer-test formulation
干预措施: AeroChamber Plus Flow-Vu spacer (Device)
结局指标
主要结局
Area Under the Plasma Concentration-curve from Zero to the Last Quantifiable Concentration (AUClast) of BGF MDI
时间窗: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
To assess that the total systemic exposure of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with AeroChamber Plus Flow-Vu spacer does not exceed that with BGF MDI HFA with AeroChamber Plus Flow-Vu spacer.
Maximum Observed Concentration (Cmax) of BGF MDI
时间窗: Day 1 and Day 2 of each treatment period (each treatment period is of 2 days)
To assess that the total systemic exposure of budesonide, glycopyrronium, and formoterol administered as BGF MDI HFO with AeroChamber Plus Flow-Vu spacer does not exceed that with BGF MDI HFA with AeroChamber Plus Flow-Vu spacer.
次要结局
- Maximum Observed Concentration (Cmax)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Area Under the Plasma Concentration-curve from Zero to the Last Quantifiable Concentration (AUClast)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Half-life Associated with Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Mean Residence Time of the Unchanged Drug in the Systemic Circulation from Zero to Infinity (MRTinf)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Apparent Total Body Clearance of Drug from Plasma After Extravascular Administration (CL/F)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Apparent Volume of Distribution at Steady State Following Extravascular Administration (Vz/F)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Number of Participants with Adverse Events(From Baseline up to 48 days)
- Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Time to Reach Maximum Observed Concentration (tmax)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))
- Terminal Rate Constant (λz)(Day 1 and Day 2 of each treatment period (each treatment period is of 2 days))