Phase I, Open-label, Single-dose, Sequential, Randomized, Crossover Study of Acalabrutinib Suspension Delivered Via Nasogastric Tube in Healthy Subjects to Evaluate Relative Bioavailability and Proton-pump Inhibitor (Rabeprazole) Effect
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Acalabrutinib and ACP-5862 plasma PK parameter: Area under plasma concentration-time curve from time zero to infinity (AUCinf)
研究概览
简要总结
This study is being conducted to support the clinical development of acalabrutinib in patients who are unable to swallow capsule and require nasogastric (NG) tube placement.
详细描述
This is an open-label, single-center, randomized, 3-period, crossover study of acalabrutinib suspension administered via NG tube in healthy subjects to evaluate the relative bioavailability and proton-pump inhibitor (rabeprazole) effect.
The study is divided in 3 periods.
Period 1 of the study is designed to investigate the effect of proton-pump inhibitor on the pharmacokinetics (PK) of acalabrutinib suspension. Period 2 and 3 of the study are designed to investigate the bioavailability of acalabrutinib suspension relative to an oral capsule formulation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provision of signed and dated, written informed consent prior to any study-specific procedures.
- •Healthy adult male and female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
- •Male subjects and their female partners/spouses must adhere to the contraception methods.
- •Female subjects must have a negative pregnancy test at screening, must not be lactating, and must be of non-childbearing potential.
- •Have a body mass index (BMI) between 18.5 and 30 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive, at screening.
排除标准
- •History or presence of any clinically significant disease (including COVID-19) or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- •History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
- •Any positive result on screening for serum hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
- •Plasma donation within 30 days of screening or any blood donation/loss more than 500 mL during the 90 days prior to screening.
- •Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 90 days prior to screening.
- •Positive screen for drugs of abuse or cotinine at screening.
- •Known or suspected history of alcohol or drug abuse, or excessive intake of alcohol as judged by the Investigator.
- •Excessive intake of caffeine-containing drinks or food as judged by the Investigator.
- •Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
- •History of a disorder which would make NG tube placement contraindicated, eg, esophageal strictures, esophageal varices, or bleeding diathesis.
- •Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections). Subjects with localized cutaneous fungal infections are eligible.
研究组 & 干预措施
Treatment Sequence 1
Participants will receive Treatment A (100 mg acalabrutinib suspension via NG administration plus 20 mg rabeprazole) in Period 1, Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 2, and Treatment C (100 mg acalabrutinib capsule) in Period 3.
干预措施: Acalabrutinib Treatment B (Drug)
Treatment Sequence 1
Participants will receive Treatment A (100 mg acalabrutinib suspension via NG administration plus 20 mg rabeprazole) in Period 1, Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 2, and Treatment C (100 mg acalabrutinib capsule) in Period 3.
干预措施: Acalabrutinib Treatment A (Drug)
Treatment Sequence 1
Participants will receive Treatment A (100 mg acalabrutinib suspension via NG administration plus 20 mg rabeprazole) in Period 1, Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 2, and Treatment C (100 mg acalabrutinib capsule) in Period 3.
干预措施: Acalabrutinib Treatment C (Drug)
Treatment Sequence 2
Participants will receive Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 1, Treatment C (100 mg acalabrutinib capsule) in Period 2, and Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 3.
干预措施: Acalabrutinib Treatment B (Drug)
Treatment Sequence 2
Participants will receive Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 1, Treatment C (100 mg acalabrutinib capsule) in Period 2, and Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 3.
干预措施: Acalabrutinib Treatment C (Drug)
结局指标
主要结局
Acalabrutinib and ACP-5862 plasma PK parameter: Area under plasma concentration-time curve from time zero to infinity (AUCinf)
时间窗: Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours (h) post-dose
To compare the AUCinf of the acala NG suspension with and without rabeprazole. To compare the AUC of the acala NG suspension with the oral capsule.
Acalabrutinib and ACP-5862 plasma PK parameter: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)
时间窗: Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose
To compare the AUClast of the acala NG suspension with and without rabeprazole. To compare the AUClast of the acala NG suspension with the oral capsule.
Acalabrutinib and ACP-5862 plasma PK parameter: Maximum observed plasma concentration (Cmax)
时间窗: Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose
To compare the Cmax of the acala NG suspension with and without rabeprazole. To compare the Cmax of the acala NG suspension with the oral capsule.
次要结局
- Acalabrutinib and ACP-5862 plasma PK parameter: Time to reach maximum observed plasma concentration (tmax)(Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose)
- Acalabrutinib and ACP-5862 plasma PK parameter: Terminal elimination rate constant (λz)(Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose)
- Acalabrutinib and ACP-5862 plasma PK parameter: Metabolite to parent ratio based on Cmax (M:P[Cmax])(Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose)
- Acalabrutinib and ACP-5862 plasma PK parameter: Area under the plasma concentration-time curve from time zero to 24 hours post-dose (AUC0-24)(Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose)
- Acalabrutinib and ACP-5862 plasma PK parameter: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2)(Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose)
- Acalabrutinib and ACP-5862 plasma PK parameter: Mean residence time of the drug in the systemic circulation from zero to infinity (MRT)(Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose)
- Number of subjects with abnormal laboratory assessments(Screening, Day -1, Days 1-2, and follow-up visit (7-10 days after last dose))
- Number of subjects with serious and non-serious adverse events(Screening (Day -28), Days -3, -2, -1, Days 1-3, and follow-up visit (7-10 days after last dose))
- Acalabrutinib and ACP-5862 plasma PK parameter: Apparent total body clearance of drug from plasma after extravascular administration (acalabrutinib only) (CL/F)(Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose)
- Acalabrutinib and ACP-5862 plasma PK parameter: Apparent volume of distribution during the terminal phase after extravascular administration (acalabrutinib only) (Vz/F)(Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose)
- Acalabrutinib and ACP-5862 plasma PK parameter: Metabolite to parent ratio based on AUCinf and/or AUClast (M:P[AUC])(Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose)
- Number of subjects with abnormal vital signs(Screening, Day -1, and Day 2)