Bioequivalence Study of Prednisolone and Dexamethasone (CORE)

University Medical Center Groningen (UMCG)

Status and phase: Unknown; Phase 1

Conditions: Healthy Volunteers

Treatments: Drug: Dexamethasone; Drug: Prednisolone

Study type: Interventional

Funder types: Other

Identifiers

NCT04733144

201900874

2019-004983-23 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to compare two different glucocorticoids, prednisolone and dexamethasone at two different doses for their organ specific effects, utilizing modern day standards.

Full description

Study design: A randomised, double blind, cross-over clinical trial.

Study population: healthy human adult volunteers including 12 males and 12 females aged 18-75 years old.

Intervention: In random order, subjects will receive 7,5 mg prednisolone for one week, directly followed by 30 mg of prednisolone for one week. After a washout period of 4 weeks (or by exception 8 weeks), subjects will receive 1,125 mg dexamethasone for one week, directly followed by 4,5 mg dexamethasone for one week.

Main study parameters/endpoints: The main study endpoint is the difference in total urinary cortisol excretion as measured in 24h-urine between the lower doses of prednisolone and dexamethasone as well as between the higher doses of prednisolone and dexamethasone.

Enrollment: 24 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Participants must be healthy with no relevant medical history and no use of medication.
• Female participants aged <50 years must be using oral contraceptives and female participants age ≥50 years must be in the postmenopausal state
• Command of the Dutch language
• Providing written IC
• BMI between 18.5 and 30 kg/m2
• Participants must be between 18 and 75 years of age

Exclusion criteria

• Potential participants who are unlikely to adhere to the study protocol (for instance subjects which have a history of substance abuse or non-compliance)

• Potential participants with a medical history of:

  1. Diseases affecting the HPA-axis: e.g. primary and secondary adrenal insufficiency, pituitary tumors, and nightshift workers
  2. Diseases affecting the HPG-axis: e.g. Cushing disease.
  3. Chronic inflammatory diseases: e.g. rheumatoid arthritis, polymyalgia rheumatic, and asthma
  4. Psychiatric diseases
  5. Diabetes

• Shift workers

• Potential participants with a kidney function <60 ml/min/1.73m2, abnormalities in liver enzymes, and/or abnormalities in thyroid function

• Potential participants who are dependent on corticosteroids, e.g. asthmatic patients, and transplant recipients

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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24 participants in 2 patient groups

Prednisolone-Dexamethasone

Active Comparator group

Description:

Participants will receive 1 week of low dose (7,5 mg) prednisolone directly followed by 1 week of high dose prednisolone (30 mg). After a wash-out period, participants in this arm will receive 1 week of low dose dexamethasone (1,125 mg) directly followed by 1 week of high dose dexamethasone (4,5 mg).

Treatment:

Drug: Dexamethasone

Drug: Prednisolone

Dexamethasone-Prednisolone

Active Comparator group

Description:

Participants will receive 1 week of low dose (1,125 mg) dexamethasone directly followed by 1 week of high dose dexamethasone (30 mg). After a wash-out period, participants in this arm will receive 1 week of low dose prednisolone (7,5 mg) directly followed by 1 week of high dose prednisolone (30 mg).

Treatment:

Drug: Dexamethasone

Drug: Prednisolone