Study of the Excretion of Orally Administered Corticosteroids for the Improval of the Detection of Said Substances in Anti-doping Controls

NCT04791345 | Unknown Phase 1

• 1 other identifier: IMIMFTCL/DACORSIN/4
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Glucocorticoids (GC) were included in the list of banned substances in sports in 1986, because of evidences of positive effects on physical performance and the important health risks associated with its consumption. Due to the fact that GC are commercialized in a variety of pharmaceutical forms and are administered in different ways, it is necessary to establish discrimination criteria to guarantee the therapeutic use of these drugs and to prevent doping. Hypothesis: Discrimination criteria between allowed and prohibited administrations of GC must be specific for each of the compounds. Further studies are needed to provide discrimination criteria related to oral administration of GC. Objectives: To conduct excretion studies with dexamethasone, methylprednisolone and deflazacort in order to define notification levels and wash-out periods after the administration of a single dose (DEX, MP and DEF) or repeated doses (DEX and MP) of these drugs. Methods: Non-randomized, open-label, pharmacokinetics clinical trial where a single dose of DEF, MP and DEX and also a multi-dose of DEX and MP will be administered orally to healthy volunteers (total n=50).

Conditions

Healthy Volunteers

Keywords

Anti-doping control; Glucocorticoids; Corticosteroids; Dexamethasone; Methylprednisolone; Deflazacort

Outcome Measures

Primary Outcomes (6)

• Urine concentration of methylprednisone

  Concentration of methylprednisone in each fraction of urine samples

  0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration

• Urine concentration of methylprednisone metabolites

  Concentration of methylprednisone metabolites in each fraction of urine samples

  0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration

• Urine concentrations of deflazacort

  Concentration of deflazacort in each fraction of urine samples

  0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration

• Urine concentrations of deflazacort metabolites

  Concentration of deflazacort metabolites in each fraction of urine samples

  0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration

• Urine concentration of dexamethasone

  Concentration of dexamethasone in each fraction of urine samples

  0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h, 120-144h post-administration

• Urine concentration of dexamethasone metabolites

  Concentration of dexamethasone metabolites in each fraction of urine samples

  0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h, 120-144h post-administration

Secondary Outcomes (23)

• Plasma concentrations of drug metabolites

  Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration

• Plasma concentrations of cortisol

  Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration

• Plasma concentrations of endogen steroids

  Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration

• Plasma concentrations of testosterone

  Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration

• Plasma concentrations of epitestosterone

  Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration

Study Arms (5)

Methylprednisone single-dose

EXPERIMENTAL

Subjects receive a single dose treatment. Urine samples will be collected until 5 days after administration in 10 fractions: 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration. Blood samples will be collected until 6 days after administration in 5 fractions: pre-administration and 24h, 48h, 72h and 120h post-administration.

Drug: Methylprednisone

Methylprednisone multiple-dose

EXPERIMENTAL

Subjects receive a multiple dose treatment. Urine samples will be collected until 7 days after administration in 20 fractions.

Drug: Methylprednisone

Deflazacort single-dose

EXPERIMENTAL

Subjects receive a single-dose treatment. Urine samples will be collected until 5 days after administration in 10 fractions: 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration. Blood samples will be collected until 6 days after administration in 5 fractions: pre-administration and 24h, 48h, 72h and 120h post-administration.

Drug: Deflazacort

Dexamethasone single-dose

EXPERIMENTAL

Subjects receive a single-dose treatment. Urine samples will be collected until 13 days after administration in 11 fractions: 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h, 120-144h post-administration. Blood samples will be collected until 9 days after administration in 6 fractions: pre-administration and 24h, 48h, 72h, 120h and 192h post-administration.

Drug: Dexamethasone

Dexamethasone multiple-dose

EXPERIMENTAL

Subjects receive a multiple dose treatment. Urine samples will be collected until 10 days after administration in 34 fractions. Blood samples will be collected until 13 days after the first administration.

Drug: Dexamethasone

Interventions

Methylprednisone DRUG

12 mg of methylprednisone (3 pills of 4 mg each) administered orally in a single dose.

Also known as: Urbason®

Methylprednisone single-dose

Deflazacort DRUG

30 mg of deflazacort (1 pill) administered orally in a single dose.

Deflazacort single-dose

Dexamethasone DRUG

4 mg of dexamethasone (1 pill) administered orally in a single dose.

Dexamethasone single-dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male volunteers aged between 18 and 55 years.
• Able to understand and accept the trial procedures and able to sign an informed consent prior to any study-mandated procedure.
• History and physical examination that demonstrate not presenting organic or psychiatric disorders.
• ECG, blood and urine tests performed before the experimental session within normal limits. Minor or occasional variations of these limits will be allowed if, in the opinion of the Principal Investigator and taking into account the state of science, they have no clinical significance, do not pose a risk to the subject and do not interfere in the product evaluation. These variations and their non-relevance will be specifically justified in writing.
• Body mass index (weight/height\^2) between 19 and 27 kg/m2 and weight between 50 and 100 kg. BMI of 27-28 kg/m2 may be included according to Principal Investigator's criteria.

You may not qualify if:

• History of allergy, idiosyncrasy, hypersensitivity or adverse reactions to glucocorticoids or any of the excipients. Serious adverse reactions to any drug.
• Contraindications to treatment with study drugs (according to the respective summary of product characteristics, SmPC).
• Clinical background or evidence of gastrointestinal, hepatic, renal disorder or others that may involve an alteration of the absorption, distribution, metabolism or excretion of the drug.
• Clinical background or evidence of psychiatric disorders, alcoholism, drug abuse or habitual consumption of psychoactive drugs.
• Having participated in another clinical trial with medication in the three months prior to the start of the study.
• Having donated blood in the three months prior to the start of the study, in the event that blood extractions are made.
• Having suffered some organic disease or major surgery in the six months prior to the start of the study.
• Clinical background or evidence of cardiovascular, respiratory, renal, hepatic, endocrine, gastrointestinal, hematological, neurological, or other acute or chronic diseases that, in the opinion of the Principal Investigator or the collaborators designated by him/her, may pose a risk to the subjects or may interfere with the objectives of the study. Especially osteoporosis, hypertension, Cushing syndrome, diabetes mellitus, and viral infections such as herpes or varicella.
• Smokers of more than 20 cigarettes a day in the 3 months before the study.
• Consumption of more than 40 g of alcohol daily.
• Consumers of more than 5 coffees, teas, cola drinks, or other stimulant drinks or with xanthines daily in the 3 months prior to the study start.
• Being unable to understand the nature, consequences of the trial and the procedures that are asked to follow.
• Positive serology for hepatitis B, C or HIV.

Sponsors & Collaborators

• Parc de Salut Mar: lead

Study Sites (1)

IMIM (Hospital del Mar Medical Research Institute)

Barcelona, 08003, Spain

RECRUITING

MeSH Terms

Interventions

Methylprednisolone; deflazacort; Dexamethasone

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Rosa Ventura Alemany, PharmD, PhD

  IMIM (Hospital del Mar Medical Research Institute)

  PRINCIPAL INVESTIGATOR

• Ana M Aldea Perona, MD, PhD

  IMIM (Hospital del Mar Medical Research Institute)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rosa Ventura Alemany, PharmD, PhD

CONTACT

+34 933 160 471; rventura@imim.es

Ana M Aldea Perona, MD, PhD

CONTACT

+34 933 160 490; aaldea@imim.es

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-center, non-randomized, open-label clinical trial in healthy male volunteers. A single dose of DEX, MP and DEF, and multiple dose of DEX and MP will be administered to different subjects.

Study Record Dates

• First Submitted: March 5, 2021
• First Posted: March 10, 2021
• Study Start: February 26, 2021
• Primary Completion: February 26, 2022
• Study Completion: February 26, 2022
• Last Updated: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)