Pharmacokinetics of Hydrocortisone After Subcutaneous Administration in Chronic Adrenal Insufficiency

Study Overview
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Brief Summary
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Patients with chronic adrenal insufficiency need to adapt their hydrocortisone replacement dose in conditions of physical or psychological stress to prevent life threatening adrenal crisis. In cases of more severe impairment or unsecure gastrointestinal absorption (e.g. gastroenteritis, severe infectious disease), parenteral administration of the hydrocortisone dose is crucial. The study is conducted to offer patients the possibility to perform hydrocortisone self administration in emergency situations in a way of administration which is easy to perform and accepted by the patient. Therefore, pharmacokinetics and safety of subcutaneous hydrocortisone administration will be studied and compared to intramuscular administration.

Official Title
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Pharmacokinetics of Hydrocortisone After Subcutaneous Administration Compared With Intramuscular Injection in Chronic Adrenal Insufficiency

Conditions
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Primary Adrenal Insufficiency

Intervention / Treatment
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* Drug: Hydrocortisone intramuscular first
* Drug: Hydrocortisone subcutaneously first


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary adrenal insufficiency under standard glucocorticoid replacement therapy due to autoimmune adrenalitis or bilateral adrenalectomy (disease duration at least 12 months), age ≥ 18 years, Patient´s written informed consent, Ability to comply with the protocol procedures Exclusion criteria Diabetes mellitus, Infectious disease with fever at time of investigation, Known intolerance to the study drug or constituents oft he study drug, Oral contraception, Known pregnancy or breast feeding, Renal failure (creatinine > 2.5 ULN)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hydrocortisone subcutaneously first<br>Hydrocortisone subcutaneously first | Drug: Hydrocortisone subcutaneously first<br>* Hydrocortisone subcutaneously first<br>* Other names: 100 mg hydrocortisone (Pfizer®) in 2 ml solvent;|
| Active Comparator: Hydrocortisone intramuscular first<br>Hydrocortisone intramuscular first | Drug: Hydrocortisone intramuscular first<br>* Hydrocortisone intramuscular first<br>* Other names: 100 mg hydrocortisone (Pfizer®) in 2 ml solvent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bioequivalence Study | pharmakokinetic data (Cmax, time to Cmax, area under the curve of serum/salivary cortisol levels) | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety | number of adverse events after subcutaneous administration of hydrocortisone | 3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adrenal insufficiency, Addison's disease