Clinical trial NCT04791345: Study of the Excretion of Orally Administered Corticosteroids for the Improval of the Detection of Said Substances in Anti-doping Controls
Official title: Study of the Excretion of Orally Administered Corticosteroids for the Improval of the Detection of Said Substances in Anti-doping Controls
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Anti-doping control
Glucocorticoids
Corticosteroids
Dexamethasone
Methylprednisolone
Deflazacort
Lead sponsor: Parc de Salut Mar
Sponsor class: OTHER
First posted: 2021-03-10
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: OTHER

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.

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.

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.

Primary outcomes:
measure: Urine concentration of methylprednisone
timeFrame: 0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration
measure: Urine concentration of methylprednisone metabolites
timeFrame: 0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration
measure: Urine concentrations of deflazacort
timeFrame: 0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration
measure: Urine concentrations of deflazacort metabolites
timeFrame: 0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h post-administration
measure: Urine concentration of dexamethasone
timeFrame: 0-4h (hours), 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h, 72-96h, 96-120h, 120-144h post-administration
measure: Urine concentration of dexamethasone metabolites
timeFrame: 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:
measure: Plasma concentrations of drug metabolites
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Plasma concentrations of cortisol
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Plasma concentrations of endogen steroids
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Plasma concentrations of testosterone
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Plasma concentrations of epitestosterone
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Plasma concentrations of androsterone
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Plasma concentrations of etiocholanolone
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Plasma concentrations of 5α-androstane-3α,17β-diol
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Plasma concentrations of 5β-androstane-3α,17β-diol
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Quotient testosterone/epitestosterone in plasma
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Quotient androsterone/testosterone in plasma
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Quotient androsterone/Etio in plasma
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Quotient 5aAdiol/5bAdiol in plasma
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Quotient 5aAdiol/ET in plasma
timeFrame: Before drug administration and at 0.5h (hours), 1h, 1.5h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 120h, 192h post-administration
measure: Hemoglobin concentration
timeFrame: At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
measure: Hematocrit
timeFrame: At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
measure: Mean corpuscular hemoglobin
timeFrame: At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
measure: Mean corpuscular volume of erythrocytes
timeFrame: At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
measure: Erythrocytes count
timeFrame: At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
measure: Standard deviation of the range of distribution of erythrocytes
timeFrame: At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
measure: Platelet count
timeFrame: At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
measure: Reticulocyte count
timeFrame: At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
measure: Fraction of immature reticulocytes
timeFrame: At -72h (hours), -48h, -24h (before first administration), and at 0h, 1h, 3h, 6h after each dose (in multiple-dose treatments)
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: IMIM (Hospital del Mar Medical Research Institute)
Study officials:
affiliation: IMIM (Hospital del Mar Medical Research Institute)
name: Rosa Ventura Alemany, PharmD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: IMIM (Hospital del Mar Medical Research Institute)
name: Ana M Aldea Perona, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: