Cysteine-lowering Treatment With Mesna
- Registration Number
- NCT04449536
- Lead Sponsor
- University of Oslo
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 25
- BMI between BMI 27-40 kg/m2
- Age between 18-55 years
- Male
- Healthy as determined by medical evaluation, medical history, physical examination, 12-lead ECG, and laboratory tests
- 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
- Veganism
- Strenuous physical activity ≥3 times every week
- Smoking
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Mesna Mesna Administration of a single oral dose of 400 mg, 800 mg, 1200 mg or 1600 mg
- Primary Outcome Measures
Name Time Method Change in plasma total cysteine concentrations following single ascending doses of oral Mesna. Several intervals during the first 12 hours after Mensa administration, and a fasting sample on days 2 and 3 Nadir plasma total cysteine concentrations
- Secondary Outcome Measures
Name Time Method 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 Maximum plasma Mesna concentration (Cmax) after a single oral Mesna dose
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 Area under the plasma Mesna concentration-time curve (AUC)0-inf after a single oral Mesna dose
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 Time to maximum plasma Mesna concentration (Tmax) after a single oral Mesna dose
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 Elimination rate constant (Kel) for Mesna after a single oral Mesna dose
Pharmacokinetic parameter - dose linearity Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3 Dose linearity of Mesna after a single oral Mesna dose
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 Estimated AUCs
Urine excretion of cysteine During the first 24 hours after Mesna administration Cumulative and fractional excretion of total cysteine and Mesna
Safety of Mesna During the first 5 days after Mesna administration Occurrence/prevalence of side effects, adverse events, and serious adverse events
Trial Locations
- Locations (1)
University of Oslo
🇳🇴Oslo, Norway