A Phase I, Single-Dose, Open-Label, Sequential, Randomised, Crossover Study to Assess the Relative Bioavailability of Different Subcutaneous Formulations of AZD6234 in Participants Living With Overweight or Obesity
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 19
- 试验地点
- 3
- 主要终点
- Maximum observed plasma concentration (Cmax)
研究概览
简要总结
This study in healthy volunteers aims to compare blood levels and side effects after administration of different formulations of AZD6234.
This study will take place at one site in Nottingham, United Kingdom, and will enrol 21 healthy men and women aged 18-55 years.
详细描述
This study in healthy volunteers aims to compare blood levels and side effects after administration of different formulations of AZD6234.
This study will take place at one site in Nottingham, United Kingdom.
It plans to enrol 21 healthy men and women aged 18-55 years.
Each volunteer will take part in 4 treatment periods and receive different formulations of AZD6234, by injection under the skin into the abdomen (stomach). In each period they'll be given a single dose without food. They'll stay in the clinic for 6 nights on 4 occasions, attend up to 10 outpatient visits, and take up to 19 weeks to finish the study.
Blood and urine samples will be collected to: measure the amount of AZD6234 and its breakdown products, do safety tests and assess the effect of the test medicine on the immune system response.
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
- •Healthy males or non-pregnant, non-lactating females aged 18 to 55 years inclusive
- •BMI of 25.0 to 35.0 kg/m2 inclusive and weight ≥50 kg
排除标准
- •History of any clinically important disease or disorder
- •History or presence of clinically significant cardiovascular, renal, hepatic, dermatological, respiratory, neurological, psychiatric or gastrointestinal disorder including a history of pancreatitis or gall stones
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the planned first dosing day
- •Clinically significant abnormal clinical chemistry, haematology, coagulation or urinalysis
- •Any clinically significant abnormal findings in vital signs
- •Any clinically significant abnormalities on 12-lead ECG
- •HbA1c ≥6.5% (≥48 mmol/mol)
- •Evidence of renal impairment
- •Females who are pregnant or lactating.
- •Any participant who has received an amylin analogue containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer)
- •Participants who report to have previously received AZD
- •Use of any prescribed or non-prescribed medication
研究组 & 干预措施
Sequence BCAD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment B in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 2 (high concentration) (Drug)
Sequence ABCD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment A in Period 1, Treatment B in Period 2, Treatment C in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 3 (Drug)
Sequence BCAD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment B in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 1 (Drug)
Sequence CABD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment C in Period 1, Treatment A in Period 2, Treatment B in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 1 (Drug)
Sequence ABCD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment A in Period 1, Treatment B in Period 2, Treatment C in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 1 (Drug)
Sequence ABCD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment A in Period 1, Treatment B in Period 2, Treatment C in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 2 (low concentration) (Drug)
Sequence CABD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment C in Period 1, Treatment A in Period 2, Treatment B in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 2 (high concentration) (Drug)
Sequence CABD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment C in Period 1, Treatment A in Period 2, Treatment B in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 2 (low concentration) (Drug)
Sequence CABD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment C in Period 1, Treatment A in Period 2, Treatment B in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 3 (Drug)
Sequence ABCD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment A in Period 1, Treatment B in Period 2, Treatment C in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 2 (high concentration) (Drug)
Sequence BCAD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment B in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 2 (low concentration) (Drug)
Sequence BCAD
Participants will receive a single SC injection of AZD6234 in each of four study periods, Treatment B in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment D in Period 4 (Where A is AZD6234 Formulation 1, B is AZD6234 Formulation 2 (low concentration), C is AZD6234 Formulation 2 (high concentration) and D is AZD6234 Formulation 3)
干预措施: AZD6234 Formulation 3 (Drug)
结局指标
主要结局
Maximum observed plasma concentration (Cmax)
时间窗: Plasma sample collection from pre- dose to 30 days post final dose
Assess relative bioavailability (rBA) by comparing the pharmacokinetics (PK) of different AZD6234 SC formulations
Area under the concentration-time curve from time 0 to the time of the last measurable concentration (AUC0-t)
时间窗: Plasma sample collection from pre- dose to 30 days post final dose
Assess relative bioavailability (rBA) by comparing the pharmacokinetics (PK) of different AZD6234 SC formulations
Area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-inf)
时间窗: Plasma sample collection from pre- dose to 30 days post final dose
Assess relative bioavailability (rBA) by comparing the pharmacokinetics (PK) of different AZD6234 SC formulations
次要结局
- Number of subjects with adverse events (AEs)/serious AEs (SAEs), and change from baseline for vital signs, electrocardiograms (ECGs), and laboratory safety tests(Through study duration, approximately 19 weeks)
- Time of maximum observed plasma concentration (tmax)(Plasma sample collection from pre- dose to 30 days post final dose)
- Total body clearance calculated after a single extravascular administration where F (fraction of dose bioavailable) is unknown (CL/F)(Plasma sample collection from pre- dose to 30 days post final dose)
- Terminal elimination half-life (t1/2)(Plasma sample collection from pre- dose to 30 days post final dose)
- Volume of distribution based on the terminal phase calculated using AUC0-inf after a single extravascular administration where F (fraction of dose bioavailable) is unknown (Vz/F)(Plasma sample collection from pre- dose to 30 days post final dose)