A Phase 1 Relative Bioavailability Study in Healthy CYP2D6 Intermediate (IM) and Extensive Metaboliser (EM) Subjects, Designed to Evaluate the Pharmacokinetic (PK) Profile of HTL0009936 Following Single Dose Administration of Modified Release (MR) Prototype Formulations
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- AUC (0-inf)
研究概览
简要总结
The purpose of this study is to find a modified release oral tablet formulation for this drug, which will be safe and well tolerated.
详细描述
The aim of the study is to develop a modified release oral tablet formulation that maintains plasma concentrations within the target therapeutic range, and is safe and tolerable.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males & females
- •Aged 18 to 65 years
- •Body mass index of 18.0 to 35.0 kg/m2
- •CYP2D6 (intermediate or extensive metabolizer)
排除标准
- •Subjects with a resting heart rate (HR) >90 bpm, and/or systolic blood pressure (BP) >150 mmHg, and/or diastolic BP >90 mmHg
- •Subjects with QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms (males) or >470 ms (females)
- •Personal or family history of long QT syndrome or sudden death
- •Subjects who are CYP2D6 (poor or ultra-rapid metabolizer)
研究组 & 干预措施
HTL0009936 modified release (MR) Formulation
Intervention: 5 different modified release formulations of HTL0009936, as a single dose
干预措施: HTL0009936 modified release (Drug)
HTL00009936 immediate release (IR) fasted
Intervention: 1 immediate release formulation of HTL0009936, as a single dose in the fasted state
干预措施: HTL0009936 immediate release (Drug)
结局指标
主要结局
AUC (0-inf)
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the area under the concentration versus time curve from time zero to extrapolated to infinity (AUC(0-inf)).
T1/2
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the apparent elimination half-life (T1/2).
Dose normalized AUC
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. In addition, if different dose levels of the same prototype are administered, dose normalized AUC (AUC/D) will be calculated.
Tlag
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the elapsed time from dosing at which HTL0009936 was first quantifiable in a concentration vs time profile (Tlag).
Tmax
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the elapsed time from dosing at which the maximum observed HTL0009936 concentration (Cmax) was apparent (Tmax)
Lambda-z
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the slope of the apparent elimination phase (Lambda-z).
Frel
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of relative bioavailability (Frel) of HTL0009936 MR prototype formulations compared to the IR reference formulation and, if applicable, MR prototype formulations in the fed state compared to fasted state.
Cmax
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of Cmax.
Concentration of HTL0009936 at 6 hours post dose (C6)
时间窗: 6 hours post dose
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of HTL0009936 concentration at 6 hours post-dose (C6)
AUC%extrap
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of percentage of AUC(0-inf) extrapolated beyond last measured time point (AUC%extrap).
AUC (0-last)
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of the area under the concentration versus time curve from time zero to the last measurable concentration (AUC(0-last))
Dose normalized Cmax
时间窗: 14 weeks
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. In addition, if different dose levels of the same prototype are administered, dose normalized Cmax (Cmax/D) will be calculated.
Concentration of HTL0009936 at 12 hours post dose (C12)
时间窗: 12 hours post dose
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of HTL0009936 concentration at 12 hours post-dose (C12)
Concentration of HTL0009936 at 24 hours post dose (C24)
时间窗: 24 hours post dose
The PK profiles of HTL0009936 Modified release oral prototype formulations in healthy CYP2D6 IM and EM subjects. Calculation of HTL0009936 concentration at 24 hours post-dose (C24)
次要结局
未报告次要终点