The purpose of the study is to find out whether food has an effect on the way the body deals with modified release hydrocortisone, and to compare with the pharmacokinetics of immediate release hydrocortisone (fasted). This information will be used to help doctors with dosing in clinical practice.
This is a phase I study in healthy male volunteers, who will be given dexamethasone to suppress their natural cortisol production. 18 will be consented for the study. They will have had a history and a physical examination, blood tests for routine safety, hepatitis C and Human Immunodeficiency Virus (HIV), drug abuse and Electrocardiograms (ECGs). Following the results of these tests and the inclusion/exclusion criteria for the study, they will be admitted to the phase I unit on the first afternoon (Day -1). They will be given dexamethasone at 22.00hrs that evening, and remain in the unit until the end of the period. Further dexamethasone doses will be given at 06:00, 12:00, and 18:00 hours on Day 1 (plus at 22:00 hours in patients given the modified release study drug). Each volunteer will be admitted for 3 periods of approximately 1.5 days, with a washout of 7 days between periods, and they will be randomised to either fast and take a single 20mg dose of immediate release hydrocortisone, to fast and take a single 20mg dose of the study medication, (a modified release hydrocortisone), or to the "fed" group, where they take a single dose of 20mg study medication, and have a highly calorific standardised breakfast. The volunteers will have cannulae to enable one pre-dose blood sample to be taken followed by 24 hour Pharmacokinetic (PK) sampling (modified release) and 12 hour PK sampling for the immediate release period. After these samples have been taken the volunteers will be able to leave the unit. There will be another assessment 3 to 5 days after study period 3 with further blood tests, assessment of any adverse events etc.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
18
Dexamethasone used to suppress endogenous cortisol secretion
single dose of 20mg modified release hydrocortisone in the absence of food
single dose of 20mg immediate release hydrocortisone in the absence of food
Chronocort Cmax
Comparison of fed and fasted Chronocort Cmax for serum cortisol.
Time frame: 24 hours
Comparison of Fed and Fasted Chronocort AUC0-t
Area under the curve from 0 to 24 hours for serum cortisol. Please note that the AUC0-t will be presented as a single figure (geometric mean) to represent exposure over time. N.B., the sampling points for Hydrocortisone are as follows: 0h, 0.25h, 0.5h, 0.75h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 8h, 10h and 12h post-dose. However, the results for Hydrocortisone will not be incorporated into the analysis for this outcome measure.
Time frame: 24 hours (at 0h, then 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 9h, 10h, 11h, 12h, 13h, 14h, 15h, 16h, 18h, 20h, 22h and 24h post-dose.)
Comparison of Fed and Fasted Chronocort Tmax
Comparison of Fed and Fasted Chronocort based on the time to achive the maximum concentration of serum cortisol
Time frame: 24 hours
Bioavailability of Chronocort® vs Hydrocortisone Tablets - Cmax
Evaluation of the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state by Cmax
Time frame: 24 hours
Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using AUC0-t
To evaluate the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state using area under the curve
Time frame: 24 hours
Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using Tmax.
To evaluate the relative bioavailability of Chronocort® and immediate release hydrocortisone at a single dose of 20 mg in the fasted state using Tmax.
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single dose of 20mg modified release hydrocortisone in the presence of food
Time frame: 24 hours