Cysteine-lowering Treatment With Mesna

Cysteine-lowering Treatment With Mesna Against Obesity: Phase I Dose-finding Study

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.

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.

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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