Drug Effect, Obesity
Conditions
Keywords
Cysteine, Phase 1, Mesna
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.
Interventions
DRUGMesna
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
Sponsors
University of Oslo
Oslo University Hospital
University of Oxford
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 - 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 - 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 |
| 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 - 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in plasma biomarker concentration - insulin | During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3 | Estimated AUC |
| Changes in plasma biomarker concentration - lipids | During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3 | Estimated AUC |
| Changes in plasma and urine sulfur amino acids and related metabolites | Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3 | Estimated AUCs |
| Changes in plasma biomarker concentration - glucose | During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3 | Estimated AUC |
Countries
Norway
Outcome results
None listed