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Cysteine-lowering Treatment With Mesna (CYLOB)

Primary Purpose

Obesity, Drug Effect

Status
Completed
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
Mesna
Sponsored by
University of Oslo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obesity focused on measuring Cysteine, Phase 1, Mesna

Eligibility Criteria

18 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

  • University of Oslo

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Mesna

Arm Description

Administration of a single oral dose of 400 mg, 800 mg, 1200 mg or 1600 mg

Outcomes

Primary Outcome Measures

Change in plasma total cysteine concentrations following single ascending doses of oral Mesna.
Nadir plasma total cysteine concentrations

Secondary Outcome Measures

Pharmacokinetic parameter - maximum plasma concentration (Cmax)
Maximum plasma Mesna concentration (Cmax) after a single oral Mesna dose
Pharmacokinetic parameter - time to maximum plasma concentration (Tmax)
Time to maximum plasma Mesna concentration (Tmax) after a single oral Mesna dose
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
Pharmacokinetic parameter - elimination rate constant (Kel)
Elimination rate constant (Kel) for Mesna after a single oral Mesna dose
Pharmacokinetic parameter - dose linearity
Dose linearity of Mesna after a single oral Mesna dose
Change in plasma cystine, free reduced cysteine, and protein bound cysteine
Estimated AUCs
Urine excretion of cysteine
Cumulative and fractional excretion of total cysteine and Mesna
Safety of Mesna
Occurrence/prevalence of side effects, adverse events, and serious adverse events

Full Information

First Posted
June 15, 2020
Last Updated
May 18, 2022
Sponsor
University of Oslo
Collaborators
Oslo University Hospital, University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT04449536
Brief Title
Cysteine-lowering Treatment With Mesna
Acronym
CYLOB
Official Title
Cysteine-lowering Treatment With Mesna Against Obesity: Phase I Dose-finding Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
November 2, 2020 (Actual)
Primary Completion Date
October 21, 2021 (Actual)
Study Completion Date
October 21, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Oslo
Collaborators
Oslo University Hospital, University of Oxford

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Drug Effect
Keywords
Cysteine, Phase 1, Mesna

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Mesna
Arm Type
Experimental
Arm Description
Administration of a single oral dose of 400 mg, 800 mg, 1200 mg or 1600 mg
Intervention Type
Drug
Intervention Name(s)
Mesna
Other Intervention Name(s)
Uromitexan
Intervention Description
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
Primary Outcome Measure Information:
Title
Change in plasma total cysteine concentrations following single ascending doses of oral Mesna.
Description
Nadir plasma total cysteine concentrations
Time Frame
Several intervals during the first 12 hours after Mensa administration, and a fasting sample on days 2 and 3
Secondary Outcome Measure Information:
Title
Pharmacokinetic parameter - maximum plasma concentration (Cmax)
Description
Maximum plasma Mesna concentration (Cmax) after a single oral Mesna dose
Time Frame
Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Title
Pharmacokinetic parameter - time to maximum plasma concentration (Tmax)
Description
Time to maximum plasma Mesna concentration (Tmax) after a single oral Mesna dose
Time Frame
Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Title
Pharmacokinetic parameter - area under the plasma concentration-time curve (AUC)
Description
Area under the plasma Mesna concentration-time curve (AUC)0-inf after a single oral Mesna dose
Time Frame
Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Title
Pharmacokinetic parameter - elimination rate constant (Kel)
Description
Elimination rate constant (Kel) for Mesna after a single oral Mesna dose
Time Frame
Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Title
Pharmacokinetic parameter - dose linearity
Description
Dose linearity of Mesna after a single oral Mesna dose
Time Frame
Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Title
Change in plasma cystine, free reduced cysteine, and protein bound cysteine
Description
Estimated AUCs
Time Frame
Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Title
Urine excretion of cysteine
Description
Cumulative and fractional excretion of total cysteine and Mesna
Time Frame
During the first 24 hours after Mesna administration
Title
Safety of Mesna
Description
Occurrence/prevalence of side effects, adverse events, and serious adverse events
Time Frame
During the first 5 days after Mesna administration
Other Pre-specified Outcome Measures:
Title
Changes in plasma and urine sulfur amino acids and related metabolites
Description
Estimated AUCs
Time Frame
Several intervals during the first 12 hours after Mesna administration, and a fasting sample on days 2 and 3
Title
Changes in plasma biomarker concentration - glucose
Description
Estimated AUC
Time Frame
During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
Title
Changes in plasma biomarker concentration - insulin
Description
Estimated AUC
Time Frame
During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3
Title
Changes in plasma biomarker concentration - lipids
Description
Estimated AUC
Time Frame
During the first 24 hours after Mesna administration, and a fasting sample on days 2 and 3

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kjetil Retterstøl, MD, PhD
Organizational Affiliation
University of Oslo
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Oslo
City
Oslo
Country
Norway

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data that support the findings of this study may be available upon reasonable request from qualified users.

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Cysteine-lowering Treatment With Mesna

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