Phase 1, First-in-human, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and PK of Single and Multiple Ascending Oral Doses of XEN1101 and Preliminary Open-label Pharmacodynamic Assessment in Healthy Subjects Addendum: Phase 1, Randomised, Multi Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Relative Bioavailability and Food Effect of Single and Multiple Ascending Doses of XEN1101 and Preliminary Drug-Drug Interaction Assessment With Itraconazole
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 130
- 试验地点
- 1
- 主要终点
- Parts 1 & 2: Resting electrocardiogram (ECG)
研究概览
简要总结
The XEN1101 Phase 1 clinical trial is a randomized, double-blind, placebo-controlled study that will evaluate the safety, tolerability and PK of both single ascending doses (SAD) and multiple ascending doses (MAD) of XEN1101 in healthy subjects. In addition to safety and PK data, the clinical trial has been designed to include a pharmacodynamic read-out by incorporating a pilot transcranial magnetic stimulation (TMS) sub-study. The TMS model sub-study is designed to demonstrate delivery of XEN1101 into the central nervous system and to observe a change in cortical excitability as measured by EEG and/or electromyographic (EMG) activity.
Part 3, 4 and 5: Phase 1, randomised, multi part study to evaluate the safety, tolerability, PK, relative bioavailability and food effect of single and multiple ascending doses of XEN1101 and Preliminary Drug-Drug Interaction Assessment with Itraconazole.
详细描述
Part 1 will study safety, tolerability, PK of single ascending doses (SAD) of XPF-008 as well as the impact and variability of single ascending doses of XPF-008 on TMS.
Part 2 will study the safety, tolerability and PK of multiple ascending doses (MAD) of XPF-008
Part 3 will explore dose proportionality of XPF-010 and confirm dosing for subsequent cohorts, and the food effect and relative bioavailability of XPF-010 compared to XPF-008.
Part 4 will explore multiple dose PK.
Part 5 will explore the drug-drug interaction of XPF-010, when given with itraconazole.
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
- Triple (Participant, Care Provider, Investigator)
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 male or females aged between 18 and 55 years inclusive with a body mass index (BMI) between 18.50 and 30.00 kg/m2
- •Must agree to use effective methods of contraception, if applicable
- •Able to swallow capsules
- •Able to provide written, personally signed and dated informed consent form (ICF)
排除标准
- •Any history of epileptic seizures
- •Any current and relevant history of significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk, affect clinical or laboratory results, or the subject's ability to participate in the study
- •Answering "yes" to any of the questions within the Columbia Suicide Severity Rating Scale
- •Mental incapacity or lingual barriers precluding adequate understanding, cooperation, and compliance with the study
- •No prescription or over-the-counter (OTC) medications (except hormonal contraception), herbal or dietary supplements OTC medications 14 days prior to dosing to study end
- •No smoking 60 days prior to dosing to study end
- •No soft drugs 3 months prior to Screening and hard drugs 2 years prior to Screening
研究组 & 干预措施
Drug: XEN1101 XPF-008 Formulation Oral
XEN1101 XPF-008 Formulation Part 1 - Single ascending dose: Single oral dose for each cohort Part 2 - Multiple ascending dose: 7 days of single oral dose daily for each cohort
干预措施: XPF-008 (Drug)
Placebo - Microcrystalline cellulose oral
Part 1- Single Ascending Dose: Single oral dose for each cohort
Part 2 - Multiple Ascending Dose: 7 days of single oral dose daily for each cohort
干预措施: Microcrystalline Cellulose (Drug)
Drug: XEN1101 XPF-008 Formulation Oral Drug: XEN1101 XPF-010 Formulation Oral
XEN1101 XPF-008 and XPF-010 Formulation Cross Over
Part 3 will explore dose proportionality of XPF-010 and confirm dosing for subsequent cohorts, and the food effect and relative bioavailability of XPF-010 compared to XPF-008
干预措施: XPF-010 (Drug)
Drug: XEN1101 XPF-010 Formulation Oral
XEN1101 XPF-010 Formulation Oral
Part 4 will explore multiple dose PK
干预措施: XPF-010 (Drug)
Drug: XEN1101 XPF-010 Formulation Oral Drug: Itraconazole 400mg Oral
XEN1101 XPF-010 Formulation + Itraconazole
Part 5 will explore the drug-drug interaction of XPF-010, when given with itraconazole (400mg, single dose, oral solution, fasted)
干预措施: Itraconazole 400mg (Drug)
结局指标
主要结局
Parts 1 & 2: Resting electrocardiogram (ECG)
时间窗: At screening (28 days prior to Day 1) through to 7 days post-final dose
To assess ECG as a criteria of safety and tolerability
Part 3b: Maximum Observed Plasma Concentration (Cmax) of XEN1101
时间窗: At screening (27 days prior to Day -1) through to 31 days post dose
To assess the Food Effect on PK (Cmax) and the relative bioavailability/comparability (Cmax) of XEN1101 following single oral doses of XPF-010 (fed), XPF-008 (fed) and XPF-010 (fasted)
Part 3b: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations
时间窗: At screening (27 days prior to Day -1) through to 31 days post dose
To evaluate the safety and tolerability of XEN1101
Part 3a: Frequency and severity of treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (SAEs), and TEAEs leading to treatment discontinuations
时间窗: At screening (27 days prior to Day -1) through to 31 days post dose
To evaluate the safety and tolerability of XEN1101 (XPF-010)
Part 3b: Area under the plasma concentration-time curve (AUC) of XEN1101
时间窗: At screening (27 days prior to Day -1) through to 31 days post dose
To assess the Food Effect on PK (AUC0-240h) and the relative bioavailability/comparability (AUC0-240h) of XEN1101 following single oral doses of XPF-010 (fed), XPF-008 (fed) and XPF-010 (fasted)
Part 4: Area under the plasma concentration-time curve (AUC) of XEN1101
时间窗: At screening (27 days prior to Day -1) through to 51 days post dose
To characterize the PK profile of XEN1101 and M11 (metabolite of XEN1101) in plasma of multiple daily oral doses of XPF-010
Parts 1 & 2: Number of Participants with Adverse Events (AEs)
时间窗: From screening (28 days prior to Day 1) through to 30 days post-final dose
To assess AEs as a criteria of safety and tolerability
Parts 1 & 2: Vital signs
时间窗: At screening (28 days prior to Day 1) through to 7 days post-final dose
To assess vital signs as a criteria of safety and tolerability
Part 3a: Maximum Observed Plasma Concentration (Cmax) of XEN1101
时间窗: At screening (27 days prior to Day -1) through to 31 days post dose
To characterize the PK profile of XEN1101 and M11 (a metabolite of XEN1101) in plasma of single ascending, oral doses of XPF-010
Part 5: Area under the plasma concentration-time curve (AUC) of XEN1101
时间窗: Day 10 and Day 11
To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole
Part 3a: Area under the plasma concentration-time curve (AUC) of XEN1101
时间窗: At screening (27 days prior to Day -1) through to 31 days post dose
To characterize the PK profile of XEN1101 and M11 (a metabolite of XEN1101) in plasma of single ascending, oral doses of XPF-010
Part 4: Maximum Observed Plasma Concentration (Cmax) of XEN1101
时间窗: At screening (27 days prior to Day -1) through to 51 days post dose
To characterize the PK profile of XEN1101 and M11 (metabolite of XEN1101) in plasma of multiple daily oral doses of XPF-010
Part 5: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations
时间窗: At screening (27 days prior to Day -1) through to 51 days post dose
To evaluate the safety and tolerability of XEN1101 (XPF-010)
Part 4: Frequency and severity of TEAEs, treatment-emergent SAEs, and TEAEs leading to treatment discontinuations
时间窗: At screening (27 days prior to Day -1) through to 51 days post dose
To evaluate the safety and tolerability of XEN1101 (XPF-010)
Part 5: Maximum Observed Plasma Concentration (Cmax) of XEN1101
时间窗: Day 10 and Day 11
To assess the PK of XEN1101 (XPF-010) in the presence and absence of itraconazole
次要结局
- Parts 1 & 2: Time to the Maximum Observed Plasma Concentration (Tmax)(Day 1 predose through to 7 days post-final dose)
- Parts 1 & 2: Terminal elimination half-life (t1/2)(Day 1 predose through to 7 days post-final dose)
- Parts 1 & 2: Maximum Observed Plasma Concentration (Cmax)(Day 1 predose through to 7 days post-final dose)
- Parts 1 & 2: Area Under the Plasma Concentration-Time Curve from Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC0-last)(Day 1 predose through to 7 days post-final dose)
- Parts 3 to 5: Cardiac Safety(At screening (27 days prior to Day -1) through to 11 days post dose for Parts 3a and 3b and at screening (27days prior to Day -1) through to Day 21)