A Phase I, Single-centre, Double-blind, Randomised, Placebo-controlled, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of Two Different Extended Release Formulations of Tablets of AZD3241 (300 mg) After Administration of Multiple Doses in Healthy Male and Female Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- AUC(0-12),ss: Area under the plasma concentration-time curve from time zero to the end of the 12-hour dosing interval at steady state.
研究概览
简要总结
To evaluate the pharmacokinetics of AZD3241 following multiple administration of 2 new, different extended release formulations of tablets of AZD3241 (300 mg), in relation to the 100 mg extended release tablet used in a previous study and potential food interaction. The safety and tolerability of AZD 3241 will also be investigated as a secondary objective. In addition to these a number of exploratory objectives will be investigated with blood sampling.
详细描述
A Phase I, Single-centre, Double-blind, Randomised, Placebo-controlled, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of Two Different Extended Release Formulations of Tablets of AZD3241 (300 mg) after Administration of Multiple Doses in Healthy Male and Female Volunteers
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older 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 male or female volunteers aged 30 to 65 years, inclusive, with suitable veins for cannulation or repeated venepuncture
- •Female volunteers must have a negative pregnancy test at Screening and on admission to the CPU, must not be lactating and must be of non childbearing potential, confirmed at Screening
- •Male volunteers must be willing to use barrier contraception ie, condoms, from the first day of dose administration until 3 months after the last dose of the IP
- •Volunteers must have a body mass index (BMI) between 18 and 30 kg/m2 and weigh at least 50 kg and no more than 100 kg
排除标准
- •History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD3241
- •Orthostatic hypotension defined as 25 mmHg decrease in systolic and/or 15 mmHg decrease in diastolic BP as measured at enrolment and/or randomisation
- •History of intolerance or hypersensitivity to mannitol
- •Prolonged QT interval corrected for heart rate using Fridericia's formula (QTcF)>450 ms or shortened QTcF<340 ms or a family history of long QT syndrome
- •Abnormal vital signs, after 10 minutes of rest in supine position, defined as any of the following:Systolic BP>140 mmHg., Diastolic BP>90 mmHg., Heart rate<40 or >85 beats per minute.
研究组 & 干预措施
1
AZD3241 300mg extended release formulation 1
干预措施: AZD3241 ER formulation 1 (Drug)
1
AZD3241 300mg extended release formulation 1
干预措施: AZD3241 Alternative titration scheme with formulation 1 or 2 (Drug)
2
AZD3241 300mg extended release formulation 2
干预措施: AZD3241 Alternative titration scheme with formulation 1 or 2 (Drug)
3
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
AUC(0-12),ss: Area under the plasma concentration-time curve from time zero to the end of the 12-hour dosing interval at steady state.
时间窗: Day 1 until 24 hours post last dose (administered on the morning of Day 8)
AUC(0-12),ss/DN: Area under the plasma concentration-time curve from time zero to the end of the 12-hour dosing interval at steady state observed with the 300 mg ER formulations normalised to a 100 mg dose of AZD3241
时间窗: Day 1 until 24 hours post last dose (administered on the morning of Day 8)
Css,max: Observed maximum plasma concentration at steady state.Css,max/DN Observed maximum plasma concentration at steady state observed with the 300 mg ER formulations normalised to a 100 mg dose of AZD3241.
时间窗: Day 1 until 24 hours post last dose (administered on the morning of Day 8)
Css,min: Observed minimum plasma concentration at steady state.Css,min/DN Observed minimum plasma concentration at steady state observed with the 300 mg ER formulations normalised to a 100 mg dose of AZD3241.
时间窗: Day 1 until 24 hours post last dose (administered on the morning of Day 8)
Css,av: Average plasma concentration during the 12-hour dosing interval at steady state calculated as follows: AUC(0-12),ss/12 h.
时间窗: Day 1 until 24 hours post last dose (administered on the morning of Day 8)
Description of fluctuation at steady-state [(Css,max-Css,min)/Css,av]
时间窗: Day 1 until 24 hours post last dose (administered on the morning of Day 8)
AUC(0-t),ss: Area under the plasma concentration-time curve from time zero to the last quantifiable time point.
时间窗: Day 1 until 24 hours post last dose (administered on the morning of Day 8)
λz,ss: Terminal elimination rate constant at steady state.
时间窗: Day 1 until 24 hours post last dose (administered on the morning of Day 8)
t½λz,ss: Half-life of terminal elimination phase at steady state.
时间窗: Day 1 until 24 hours post last dose (administered on the morning of Day 8)
次要结局
- Description of the safety and tolerability profile in terms of Adverse Events of 8 days of administration of AZD3241, up to steady state (300 mg twice daily), of 2 new, different extended release tablets of AZD3241 (300 mg), including initial titration.(Day 1 to Day 8)