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

NCT ID: NCT04791345

Last Updated: 2021-04-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-26
• Study Completion Date: 2022-02-26

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).

Detailed Description

The World Anti-Doping Agency (WADA) has established a general notification level of 30 ng/mL for GC to discriminate allowed and not allowed administrations. However, recent studies have proven that the use of a unique criteria is not adequate given the diversity of administration routes, doses and pharmacokinetics and pharmacodynamics properties of each drug.

The goal of this study is to conduct additional studies using dexamethasone (DEX), methylprednisolone (MP) and deflazacort (DEF) in order to generate additional data of urinary concentrations and wash-out periods after single and repeated oral doses of these drugs.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Methylprednisone single-dose

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.

Group Type: EXPERIMENTAL

Methylprednisone

Intervention Type: DRUG

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

Methylprednisone multiple-dose

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

Group Type: EXPERIMENTAL

Methylprednisone

Intervention Type: DRUG

12 mg of methylprednisone (3 pills of 4 mg each) administered orally every 24 hours during 3 days.

Deflazacort single-dose

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.

Group Type: EXPERIMENTAL

Deflazacort

Intervention Type: DRUG

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

Dexamethasone single-dose

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.

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

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

Dexamethasone multiple-dose

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.

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

2 mg of dexamethasone (1/2 pill) administered orally every 12 hours during 5 days.

Interventions

Methylprednisone

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

Intervention Type: DRUG

Methylprednisone

12 mg of methylprednisone (3 pills of 4 mg each) administered orally every 24 hours during 3 days.

Intervention Type: DRUG

Deflazacort

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

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

Dexamethasone

2 mg of dexamethasone (1/2 pill) administered orally every 12 hours during 5 days.

Intervention Type: DRUG

Other Intervention Names

Urbason®; Urbason®

Eligibility Criteria

Inclusion Criteria

• 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.

• 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.
• Having taken medication regularly in the month prior to the study sessions -in case of glucocorticoids 3 months prior- with the exception of vitamins, herbal remedies or dietary supplements that, in the opinion of the Principal Investigator or the collaborators designated by him/her, may not pose a risk to the subjects or may not interfere with the objectives of the study. Treatment with a single dose of symptomatic medication in the week prior to the study sessions will not be a reason for exclusion if it is assumed that the drug has been completely eliminated on the day of the experimental session.
• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Parc de Salut Mar

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rosa Ventura Alemany, PharmD, PhD

Role: PRINCIPAL_INVESTIGATOR

IMIM (Hospital del Mar Medical Research Institute)

Ana M Aldea Perona, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

IMIM (Hospital del Mar Medical Research Institute)

Locations

IMIM (Hospital del Mar Medical Research Institute)

Barcelona, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Rosa Ventura Alemany, PharmD, PhD

Role: CONTACT

rventura@imim.es

+34 933 160 471

Ana M Aldea Perona, MD, PhD

Role: CONTACT

aaldea@imim.es

+34 933 160 490

Facility Contacts

Ana M Aldea Perona, MD, PhD

Role: primary

aaldea@imim.es

+34933160490

Other Identifiers

IMIMFTCL/DACORSIN/4

Identifier Type: -

Identifier Source: org_study_id