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| Name | Class |
|---|---|
| Oslo University Hospital | OTHER |
| University of Oxford | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Mesna | Experimental | Administration of a single oral dose of 400 mg, 800 mg, 1200 mg or 1600 mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mesna | Drug | 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 |
|
| 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 |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in plasma and urine sulfur amino acids and related metabolites | Estimated AUCs | Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3 |
| Changes in plasma biomarker concentration - glucose |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kjetil Retterstøl, MD, PhD | University of Oslo | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Oslo | Oslo | Norway |
Data that support the findings of this study may be available upon reasonable request from qualified users.
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D015080 | Mesna |
| ID | Term |
|---|---|
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
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|
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 |
Estimated AUC
| During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3 |
| Changes in plasma biomarker concentration - insulin | Estimated AUC | During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3 |
| Changes in plasma biomarker concentration - lipids | Estimated AUC | During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3 |
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |