A Randomised Open Label Exploratory, Safety and Tolerability Study With PP100-01 in Patients Treated With the 12-hour Regimen of N-Acetylcysteine for Paracetamol/Acetaminophen Overdose (The POP Trial)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Safety Events
研究概览
简要总结
Investigate the safety and tolerability of PP100-01 add-on treatment to the 12hr NAC treatment regime in patients treated for paracetamol/acetaminophen overdose (POD) when NAC treatment is initiated before 24hours post POD.
详细描述
The study will be an open label, randomised, exploratory, rising dose design, NAC controlled, phase 1 safety and tolerability study in patients treated with NAC for paracetamol/acetaminophen overdose.
Entry into the study will depend on the patient's blood results confirming the need for NAC. A total of 24 patients will be assigned into one of 3 dosing cohorts of 8 patients (N=6 for PP100-01 and NAC; N=2 for NAC alone).
The study will primarily evaluate safety and tolerability for treatment with PP100-01 in combination with NAC as compared to NAC alone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any patient with capacity admitted to hospital within 24 hrs either a single acute POD or more than one dose of paracetamol (staggered) and deemed to require treatment with NAC.
- •Provision of written informed consent
- •Males and females of at least 16 years of age
排除标准
- •Patients that do not have the capacity to consent to participate in the study
- •Patients detained under the Mental Health Act or deemed unfit by the Investigator to participate due to mental health.
- •Patients with known permanent cognitive impairment
- •Patients who are pregnant or nursing
- •Patients who have previously participated in the study
- •Unreliable history of POD
- •Patients presenting after 24hrs of POD
- •Patients who take anticoagulants (e.g. warfarin) therapeutically or have taken an overdose of anticoagulants
- •Patients who, in the opinion of the responsible clinician/nurse, are unlikely to complete the full course of NAC e.g. expressing wish to self-discharge
- •Non-English speaking patients. (Study information material will only be produced in English in view of the known and stable demographic of the Edinburgh self-harm population).
研究组 & 干预措施
PP100-01 (Calmangafodipir)+ NAC
In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive:
- Group A: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC
- Group B: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC
- Group C: PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC
PP100-01 treatment is administered intravenously over 5 minutes.
干预措施: PP100-01 (calmangafodipir) (Drug)
PP100-01 (Calmangafodipir)+ NAC
In addition to the standard care NAC regime, participants will be allocated into a dosing cohort to receive:
- Group A: PP100-01 (2 umol/kg calmangafodipir) after the "loading" dose of NAC
- Group B: PP100-01 (5 umol/kg calmangafodipir) after the "loading" dose of NAC
- Group C: PP100-01 (10 umol/kg calmangafodipir) after the "loading" dose of NAC
PP100-01 treatment is administered intravenously over 5 minutes.
干预措施: Acetylcysteine (Drug)
结局指标
主要结局
Safety Events
时间窗: 90 days
Adverse Events and Serious Adverse Events
次要结局
- ALT(U/L)(20 hours)
- INR(value at 20 hours divided by baseline value for each patient)
- Additional NAC Infusion(Additional NAC at 12 hour)
- K18 (U/L)(Ratio - value at 20 hours divided by baseline value for each patient)
- K18(U/L)(10 hours)
- ccK18 (U/L)(Ratio - value at 20 hours divided by baseline value for each patient)
- miR-122 (Delta Count)(20 hours)
- miR-122 (Copies/mcL)(Ratio - value at 20 hours divided by baseline value for each patient)
- miR-122(Copies/mcL)(10 hours)