A Phase I, Open-Label, Single and Multiple Dose (Twice-Daily), Clinical Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 μg Administered by Inhalation in Healthy Chinese Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf)
研究概览
简要总结
A Phase I, single centre, open-label study to investigate the pharmacokinetics (PK), safety and tolerability of single and multiple twice daily doses of inhaled Aclidinium Bromide in healthy Chinese male and female subjects.
详细描述
Screening will be performed within 21 days of dosing on Day 1. Eligible participants will be admitted to the trial center on Day -1.
Subjects will receive single dose on Day 1, twice daily regimen is from D5 to D8, and only morning dose will be given on Day 9.
During treatment period, from Day 1 through Day 11 at Visit 2, safety measurements (blood pressure, 12-lead ECG; and AE/SAE monitoring) and blood samples for PK assessments will be collected at predetermined time points.
Clinical laboratory tests (haematology, serum biochemistry and urinalysis) will be performed under fasting conditions at Day -1 at Visit 2.
A follow-up visit will be performed on Day 15.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Ability to communicate with medical team and staff, willing to participate in the trial, willing to give written informed consent, and comply with the trial restrictions.
- •Healthy subjects: Chinese men or non-pregnant, non-lactating women, 18 through 45 years old at Visit 1 (Screening).
- •Have a body mass index (BMI) ≥19 kg/m2 and ≤ 26 kg/m2
- •Resting heart rate ≥ 50 beats per minute (bpm) and ≤ 100 bpm at Visit 1 (Screening) and at admission to the unit on Day -1 at Visit
- •Non-smoker (never smoked or has not smoked within 2 years prior to the first dose of investigational product [IP]).
- •Demonstrate satisfactory technique in the use of the DPI at screening.
排除标准
- •History of any significant drug allergy or hypersensitivity to aclidinium bromide or other muscarinic antagonists.
- •Have abnormal and clinically significant results on the physical examination, medical history, serum biochemistry, haematology, or urinalysis at Visit 1 (Screening).
- •Sustained resting systolic blood pressure ≥ 140 or ≤ 90 mmHg and resting diastolic blood pressure ≥ 90 or ≤ 50 mmHg at Visit 1 (Screening) or Day -1 at Visit
- •Electrocardiogram (ECG) showing corrected QT interval (QTc) using Fridericia's correction (QTcF) ≥ 450 msec for male participants and ≥460 msec for female participants as indicated in the centralised reading report assessed at Screening (Visit 1).
- •Have a history of alcohol or substance abuse within the previous 5 years, as reported by the participants.
- •Positive results for drugs of abuse at Visit 1 (Screening).
- •Positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody and/or human immunodeficiency virus (HIV) antibodies at Visit 1 (Screening).
- •Use of any medication within 2 weeks or within the equivalent time of 5 half-lives of taking the last dose (whichever is longer) before the first dose of IP, or hormonal drug products and traditional Chinese medicines within 30 days before the first dose of IP.
- •Have consumed caffeine or any grapefruit-containing products within 48 hours or alcohol within 72 hours before Day -
- •Participation in any other clinical investigation using an experimental drug requiring repeated blood or plasma draws within 60 days of Day 1 at Visit
- •Have participated in a blood/plasma donation or blood loss greater than 400 mL within 90 days, or greater than 200 mL within 30 days prior to screening (Visit 1).
- •Recent history of a disease or condition that would result in any residual upper respiratory airways/lung inflammatory process or residual limited lung function at the time of Day 1 at Visit
- •History of confirmed COVID-19 infection.
- •Have any gastrointestinal, hepatic, or renal condition that might affect the absorption, distribution, biotransformation, or excretion of aclidinium bromide.
- •Inability to be venipunctured or tolerate venous access as determined by the PI or designee.
- •Participants unable to give their consent, or participants of consenting age but under guardianship, or vulnerable participants.
- •In the opinion of the PI, participants who are unlikely to comply with the protocol requirements, instructions, and trial-related restrictions.
- •Participant is a relative of the Investigator or any sub-investigator, research assistant, pharmacist, trial coordinator, or other staff or directly involved in the conduct of the clinical trial.
- •Any other conditions that, in the Investigator's opinion, might have indicated the participant to be unsuitable for the study (e.g. confirmed/suspected COVID-19)
研究组 & 干预措施
Aclidinium Bromide 400 μg
One inhalation from the 400 μg Aclidinium Bromide inhaler.
干预措施: Aclidinium Bromide 400 μg (Drug)
结局指标
主要结局
Mean Residence Time of the Unchanged Drug in the Systemic Circulation (MRTinf)
时间窗: Day 1
Characterization of MRTinf, of aclidinium bromide after single dose of aclidinium bromide in healthy Chinese participants.
Accumulation Ratio for Cmax [Rac(Cmax)]
时间窗: Day 9
Characterization of Rac(Cmax), of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. Rac(Cmax) is caculated as a ratio for Cmax estimated as (ratio of Css,max on Day 9/Cmax on Day 1).
Accumulation Ratio for Cmin (Rac[Cmin])
时间窗: Day 9
Characterization of Rac(Cmin), of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. Rac(Cmin) is calculated as ratio for Cmin estimated as (ratio of Css, Cmin on Day 9/ Cmin on Day 1)
Accumulation Ratio for AUCτ (Rac[AUC])
时间窗: Day 9
Characterization of Rac(AUC), of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. Rac(AUC), calculated as ratio of AUC(0-12) on day 9 and AUC0-12 on Day 1.
Fluctuation Index During a Dosing Interval (%Fluc)
时间窗: Day 9
Characterization of %Fluc, of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants. The %Fluc index is estimated as 100 x (Cmax- Cmin)/Cav.
Volume of Distribution (Apparent) Following Extravascular Administration Based on Terminal Phase (Vz/F)
时间窗: Day 1 and Day 9
Characterization of Vz/F, of aclidinium bromide after single and multiple doses of aclidinium bromide in healthy Chinese participants.
Average Drug Concentration Over a Dosing Interval (Cavg)
时间窗: Day 9
Characterization of Cavg, of aclidinium bromide and its metabolites after multiple doses of aclidinium bromide in healthy Chinese participants.
Maximum Observed Plasma Concentration (Cmax)
时间窗: Day 1 and Day 9
Characterization of Cmax, taken directly from the individual concentration-time curve after single dose or multiple dose.
Half-life Associated With Terminal Slope of a Semi-logarithmic Concentration-time Curve (t½λz)
时间窗: Day 1 and Day 9
Characterization of t½λz, of aclidinium bromide and its metabolites after single and multiple doses of aclidinium bromide in healthy Chinese participants.
Time to Reach Maximum Observed Concentration (Tmax)
时间窗: Day 1 and Day 9
Characterization of Tmax, taken directly from the individual concentration-time curve after single dose or multiple dose.
Area Under the Concentration-time From Time 0 to 12 Hours Post-dose [AUC(0-12)]
时间窗: Day 1 and Day 9
The AUC(0-12) of aclidinium bromide and its metabolites after single dose of aclidinium bromide in healthy Chinese participants is investigated. Description of the AUC(0-12), partial area under the concentration- time curve in the dose interval after single dose or multiple dose.
Area Under the Concentration-time From Zero to the Last Quantifiable Concentration (AUClast)
时间窗: Day 1 and Day 9
Characterization of AUClast, taken directly from the individual concentration-time curve after single dose or multiple dose.
Apparent Total Body Clearance From Plasma After Extravascular Administration (CL/F)
时间窗: Day 1 and Day 9
Characterization of CL/F, of aclidinium bromide after single and multiple doses of aclidinium bromide in healthy Chinese participants.
Minimum Observed Drug Concentration (Cmin)
时间窗: Day 1 and Day 9
Characterization of Cmin, taken directly from the individual concentration-time curve after single dose or multiple dose.
Area Under the Concentration-time From Zero to Infinity (AUCinf)
时间窗: Day 1
Characterization of AUCinf (single dose). Area under the concentration time curve from time zero extrapolated to infinity. AUC(0-∞) is estimated by AUC(last) + Clast/λz where Clast is the last observed quantifiable concentration.
次要结局
- Number of Participants With Adverse Events (AEs)(From Screening (Day -21 to Day -2) until the follow-up visit (Day 15))