Cysteine-lowering Treatment With Mesna

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Obesity, Drug Effect

Intervention / Treatment
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* Drug: Mesna


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesna<br>Administration of a single oral dose of 400 mg, 800 mg, 1200 mg or 1600 mg | Drug: Mesna<br>* Administration of a single oral dose, using film-coated tablets of either 400 mg or 600 mg or a combination of maximum 3 tablets up to a maximum of 1600 mg<br>* Other names: Uromitexan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma total cysteine concentrations following single ascending doses of oral Mesna. | Nadir plasma total cysteine concentrations | Several intervals during the first 12 hours after Mensa administration, and a fasting sample on days 2 and 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameter - maximum plasma concentration (Cmax) | Maximum plasma Mesna concentration (Cmax) after a single oral Mesna dose | 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) | Time to maximum plasma Mesna concentration (Tmax) after a single oral Mesna dose | 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) | Area under the plasma Mesna concentration-time curve (AUC)0-inf after a single oral Mesna dose | 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) | Elimination rate constant (Kel) for Mesna after a single oral Mesna dose | Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3 | 
| Pharmacokinetic parameter - dose linearity | Dose linearity of Mesna after a single oral Mesna dose | 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 | Estimated AUCs | Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3 | 
| Urine excretion of cysteine | Cumulative and fractional excretion of total cysteine and Mesna | During the first 24 hours after Mesna administration | 
| Safety of Mesna | Occurrence/prevalence of side effects, adverse events, and serious adverse events | During the first 5 days after Mesna administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cysteine, Phase 1, Mesna