Cysteine-lowering Treatment With Mesna Against Obesity: Phase I Dose-finding Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Change in plasma total cysteine concentrations following single ascending doses of oral Mesna.
研究概览
简要总结
The primary objective of this study is to determine the efficacy of the drug Mesna® (Uromitexan) in healthy participants with overweight or obesity with respect to change in plasma concentrations of total cysteine, following single ascending doses of oral Mesna.
详细描述
In both animal experiments and human studies, cysteine in the blood is strongly associated with obesity. In rodents, changes in cysteine induced by dietary means are accompanied by changes in fat mass.
In this phase I, single ascending dose study the investigators will determine the effects of Mesna in healthy volunteers with overweight and obesity with focus on its effects on plasma total cysteine concentrations. The aim of this dose-finding clinical trial is to determine the lowest single oral Mesna dose that will lower plasma total cysteine concentrations by 30% using pharmacokinetic (PK)/ pharmacodynamic (PD) modelling. The investigators will further evaluate the effect of Mesna on plasma cysteine fractions and related metabolites, urinary cysteine excretion, safety and adverse drug reactions, and plasma biomarkers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •BMI between BMI 27-40 kg/m2
- •Age between 18-55 years
- •Healthy as determined by medical evaluation, medical history, physical examination, 12-lead ECG, and laboratory tests
排除标准
- •Presence of chronic disease
- •Chronic drug use
- •Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing
- •Strenuous physical activity ≥3 times every week
研究组 & 干预措施
Mesna
Administration of a single oral dose of 400 mg, 800 mg, 1200 mg or 1600 mg
干预措施: Mesna (Drug)
结局指标
主要结局
Change in plasma total cysteine concentrations following single ascending doses of oral Mesna.
时间窗: Several intervals during the first 12 hours after Mensa administration, and a fasting sample on days 2 and 3
Nadir plasma total cysteine concentrations
次要结局
- Pharmacokinetic parameter - maximum plasma concentration (Cmax)(Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3)
- Pharmacokinetic parameter - area under the plasma concentration-time curve (AUC)(Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3)
- Pharmacokinetic parameter - time to maximum plasma concentration (Tmax)(Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3)
- Pharmacokinetic parameter - elimination rate constant (Kel)(Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3)
- Pharmacokinetic parameter - dose linearity(Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3)
- Change in plasma cystine, free reduced cysteine, and protein bound cysteine(Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3)
- Urine excretion of cysteine(During the first 24 hours after Mesna administration)
- Safety of Mesna(During the first 5 days after Mesna administration)
研究者
Kathrine Vinknes
Researcher and Project manager
University of Oslo