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

Healthy Volunteers Clinical Trial

— DACORSIN/4  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04791345
• Other study ID #: IMIMFTCL/DACORSIN/4
• Status: Recruiting
• Phase: Phase 1
• Start date: February 26, 2021
• Est. completion date: February 26, 2022

Study information

• Verified date: March 2021
• Source: Parc de Salut Mar
• Contact: Rosa Ventura Alemany, PharmD, PhD
• Phone: +34 933 160 471
• Email: rventura[@]imim.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: February 26, 2022
• Est. primary completion date: February 26, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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.

Exclusion Criteria:

• Failure to meet inclusion 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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Methylprednisone
12 mg of methylprednisone (3 pills of 4 mg each) administered orally in a single dose.
• Methylprednisone
12 mg of methylprednisone (3 pills of 4 mg each) administered orally every 24 hours during 3 days.
• Deflazacort
30 mg of deflazacort (1 pill) administered orally in a single dose.
• Dexamethasone
4 mg of dexamethasone (1 pill) administered orally in a single dose.
• Dexamethasone
2 mg of dexamethasone (1/2 pill) administered orally every 12 hours during 5 days.

Locations

Country	Name	City	State
Spain	IMIM (Hospital del Mar Medical Research Institute)	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Parc de Salut Mar

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Plasma concentrations of drug metabolites	Concentrations of drug metabolites (DEX, MP, DEF) in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Plasma concentrations of cortisol	Concentrations of cortisol in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Plasma concentrations of endogen steroids	Concentrations of endogen steroids in plasma [testosterone (T), epitestosterone (E), androsterone (A), etiocholanolone (Etio), 5a-androstane-3a,17ß-diol (5aAdiol), 5ß-androstane-3a,17ß-diol (5bAdiol), and the quotients T/E, A/T, A/Etio, 5aAdiol/5bAdiol and 5aAdiol/ET]	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Plasma concentrations of testosterone	Concentrations of testosterone in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Plasma concentrations of epitestosterone	Concentrations of epitestosterone in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Plasma concentrations of androsterone	Concentrations of androsterone in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Plasma concentrations of etiocholanolone	Concentrations of etiocholanolone (Etio) in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Plasma concentrations of 5a-androstane-3a,17ß-diol	Concentrations of 5a-androstane-3a,17ß-diol (5aAdiol) in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Plasma concentrations of 5ß-androstane-3a,17ß-diol	Concentrations of 5ß-androstane-3a,17ß-diol (5bAdiol) in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Quotient testosterone/epitestosterone in plasma	Concentrations of testosterone/epitestosterone (T/E) in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Quotient androsterone/testosterone in plasma	Concentrations of androsterone/testosterone (A/T) in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Quotient androsterone/Etio in plasma	Concentrations of androsterone/etiocholanolone (A/Etio) in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Quotient 5aAdiol/5bAdiol in plasma	Concentrations of 5a-androstane-3a,17ß-diol/5ß-androstane-3a,17ß-diol (5aAdiol/5bAdiol) in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Quotient 5aAdiol/ET in plasma	Concentrations of 5a-androstane-3a,17ß-diol/etiocholanolone (5aAdiol/ET) in plasma	Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
Secondary	Hemoglobin concentration	Variation of hemoglobin concentrations in blood	At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
Secondary	Hematocrit	Variation of hematocrit value in blood	At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
Secondary	Mean corpuscular hemoglobin	Variation of mean corpuscular hemoglobin (MCH) levels in blood	At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
Secondary	Mean corpuscular volume of erythrocytes	Variation of mean corpuscular volume of erythrocytes (MCV) levels in blood	At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
Secondary	Erythrocytes count	Variation of erythrocytes count in blood	At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
Secondary	Standard deviation of the range of distribution of erythrocytes	Variation of standard deviation of the range of distribution of erythrocytes	At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
Secondary	Platelet count	Variation of platelet count in blood	At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
Secondary	Reticulocyte count	Variation of reticulocyte count in blood	At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
Secondary	Fraction of immature reticulocytes	Variation of immature reticulocytes fraction in blood	At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)