A Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of AZD2693.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 35
- 试验地点
- 3
- 主要终点
- PK parameters AUCinf
研究概览
简要总结
Subcutaneous administration of AZD2693 single dose in participants with hepatic impairment
详细描述
This is a Phase I, multicentre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD2693 administered as an subcutaneous injection in male and female participants with mild, moderate, or severe hepatic impairment compared with male and female participants with normal hepatic function (as control). Eight participants with mild impairment (CP Class A); 8 participants with moderate impairment (CP Class B); 8 participants with severe impairment (CP Class C); and 8 to12 participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired participants are planned for study intervention with the goal of having at least 6 evaluable participants within each group. Study participants who self-withdraw after study intervention may be replaced to ensure that at least 6 participants per group are evaluable and complete the study per protocol. An evaluable participant is defined as having adequate plasma PK profile to meet the primary study objective. Child-Pugh scoring, detailed in Table 2, will be used to determine the level of hepatic impairment. Participants will be enrolled into the following groups based on their CP classification score as determined at screening: Group 1: Participants with mild hepatic impairment (CP Class A, score of 5 or 6).
Group 2: Participants with moderate hepatic impairment (CP Class B, score of 7 to 9).
Group 3: Participants with severe hepatic impairment (CP Class C, score of 10 to 15).
Group 4: Participants with normal hepatic function.
Study Arms and Duration:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Hepatic:
- •Participant with a diagnosis of chronic and stable hepatic impairment
- •For Healthy:
- •Participant with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or 12-lead ECGs,
- •All participants:
- •- Body weight ≥ 50 kg; BMI within the range of 18.0 to 40.0 kg/m2 (inclusive) as measured at screening
排除标准
- •Participant with impaired hepatic function has eGFR < 60 mL/minute/1.73 m2 and participant with normal hepatic function has eGFR < 90 mL/minute/1.73 m2
- •Positive test for HIV at screening
- •History or presence of clinically significant thyroid disease
- •History or presence of clinically significant or unstable medical or psychiatric condition
- •History of any major surgical procedure within 30 days prior to study intervention
研究组 & 干预措施
Group 3
Participants with severe hepatic impairment (CP Class C, score of 10 to 15)
干预措施: AZD2693 (Drug)
Group 1
Participants with mild hepatic impairment (CP Class A, score of 5 or 6)
干预措施: AZD2693 (Drug)
Group 2
Participants with moderate hepatic impairment (CP Class B, score of 7 to 9)
干预措施: AZD2693 (Drug)
Group 4
Participants with normal hepatic function matched on a group level regarding age, body weight, and sex to the impaired groups
干预措施: AZD2693 (Drug)
结局指标
主要结局
PK parameters AUCinf
时间窗: 85 days
area under the concentration-time curve (AUC) from zero to infinity (AUCinf)
PK parameters AUClast
时间窗: 85 days
area under the concentration-time curve from time zero to last time of quantifiable concentration
PK parameters Cmax
时间窗: 85 days
maximum observed plasma concentration
次要结局
- PK parameters fe(85 days)
- PK parameters tlast(85 days)
- PK parameters t1/2λz(85 days)
- PK Parameters Vz/F(85 days)
- PK parameters Ae(85 days)
- PK parameters tmax(85 days)
- PK parameters CL/F(85 days)
- PK parameters CLR(85 days)