A Phase I, Randomized, Single-dose, 3-Period, Open-Label Study to Assess the Pharmacokinetic Formulation Bridging, Safety, and Food Effect of Different Oral Formulations of AZD5004 in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 65
- 试验地点
- 2
- 主要终点
- Area under concentration-time curve from time 0 extrapolated to infinity (AUCinf)
研究概览
简要总结
The purpose of this study is to assess the pharmacokinetics (PK), safety and tolerability of different oral formulations of AZD5004, and to evaluate the effect of food on these formulations in healthy participants.
详细描述
This is a Phase I, randomized, single-dose, 2 part, 3-period, open-label study.
There will be 2 Parts (Part A and Part B). In each part, participants will be randomized to a treatment sequence in each cohort. In Period 1, participants in Part A and Part B will receive Regimen A (AZD5004 Formulation 1 [reference]). In Periods 2 and 3, participants in Part A will receive Regimen B or Regimen C (AZD5004 Formulation 5) and participants in Part B will receive Regimen D or Regimen E per assigned treatment sequence.
The study will comprise:
- A Screening Period of maximum 28 days
- 3 Treatment Periods during which participants will be resident at the Clinical Unit
- A final Follow-up Visit within 3 to 7 days after being discharged.
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
- 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
- •Main Inclusion Criteria:
- •Participants suitable veins for cannulation or repeated venipuncture.
- •All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
- •Female participants:
- •of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception, to avoid pregnancy.
- •of non-childbearing potential must be confirmed at the Screening Visit.
- •Male participants:
- •Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
- •Additional contraception must be used for the sexual partners of male study participants throughout the clinical study.
- •Have a Body Mass Index (BMI) of ≥ 23 kg/m2 but not exceeding 35 kg/m2 inclusive (at the time of Screening) and weigh at least 60 kg.
排除标准
- •History of any clinically important disease or disorder which, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
- •Any clinically significant illness, medical/surgical procedure, or trauma
- •Participants who have a special dietary requirement and who are unable/unwilling to follow a uniform diet.
- •Participants positive for anti- hepatitis B core antibody (anti-HBc) or anti-hepatitis C Virus Antibody (anti-HCV).
- •Participants who are on or are planning to undertake a weight loss program during the study period.
- •Abnormal vital signs, after 10 minutes supine rest, at Screening and/or admission to the Clinical Unit.
- •Positive screen for drugs of abuse, or alcohol or cotinine (nicotine).
- •Any laboratory values with the deviations specified in protocol and clinically important abnormalities in clinical chemistry, hematology, or urinalysis results.
研究组 & 干预措施
Cohort B: Treatment Sequence AED
Participants will receive three treatments in sequence: Regimen A (formulation 1, fasted state), Regimen E (formulation 6, fed state), followed by Regimen D (formulation 6, fasted state).
干预措施: AZD5004 (Drug)
Cohort A: Treatment Sequence ABC
Participants will receive three treatments in sequence: Regimen A (formulation 1, fasted state), Regimen B (formulation 5, fasted state), followed by Regimen C (formulation 5, fed state) of AZD5004.
干预措施: AZD5004 (Drug)
Cohort B: Treatment Sequence ADE
Participants will receive three treatments in sequence: Regimen A (formulation 1, fasted state), Regimen D (formulation 6, fasted state), followed by Regimen E (formulation 6, fed state).
干预措施: AZD5004 (Drug)
Cohort A: Treatment Sequence ACB
Participants will receive three treatments in sequence: Regimen A (formulation 1, fasted state), Regimen C (formulation 5, fed state), followed by Regimen B (formulation 5, fasted state) of AZD5004.
干预措施: AZD5004 (Drug)
结局指标
主要结局
Area under concentration-time curve from time 0 extrapolated to infinity (AUCinf)
时间窗: From Day 1 to Day 22
To evaluate the PK (AUCinf) and assess the effect of food on the PK of different formulations of AZD5004 following single oral administration in healthy participants
Area under concentration-curve from time 0 to the time of last quantifiable concentration (AUClast)
时间窗: From Day 1 to Day 22
To evaluate the PK (AUClast) and assess the effect of food on the PK of different formulations of AZD5004 following single oral administration in healthy participants
Maximum observed concentration (Cmax)
时间窗: From Day 1 to Day 22
To evaluate the PK (Cmax) and assess the effect of food on the PK of different formulations of AZD5004 following single oral administration in healthy participants
次要结局
- Time of maximum observed concentration (tmax)(From Day 1 to Day 22)
- Terminal rate constant (λz)(From Day 1 to Day 22)
- Terminal elimination half-life (t½λz)(From Day 1 to Day 22)
- Total body clearance calculated after a single extravascular administration where F (fraction of dose bioavailable) is unknown (CL/F)(From Day 1 to Day 22)
- Apparent volume of distribution based on the terminal phase calculated using AUC(0-inf) after a single extravascular administration where F (fraction of dose bioavailable) is unknown (Vz/F)(From Day 1 to Day 22)
- Time of last measurable observed concentration (tlast)(From Day 1 to Day 22)
- R AUC (Ratio of test treatment to reference based on AUC)(From Day 1 to Day 22)
- R Cmax (Ratio of test treatment to reference based on Cmax)(From Day 1 to Day 22)
- F AUClast (Relative bioavailability based on AUClast)(From Day 1 to Day 22)
- Number of participants with adverse events (AEs), serious AEs and AESIs (adverse events of special interest)(Up to Follow up (3 to 7 days after discharge))