Conditions: Healthy
Keywords: subjects
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 18
Healthy volunteers: yes

Brief summary:
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.

Detailed description:
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.

Arms:
arm 1: Volunteers will be admitted, take dexamethasone at 22.00hrs, fast overnight, and receive a high fat, high calorie breakfast on the morning of Day 1. Thirty minutes after the start of the breakfast they will receive 20mg of modified release hydrocortisone with 200 millilitres of water, and no further food for 4 hours, water will be allowed from 1 hour after the food. Further dexamethasone doses will be given at 06:00, 12:00, 18:00 and 22:00 hours on Day 1. One baseline pharmacokinetics (PK) sample will be taken starting prior to the dose and then over 24 hours (29 samples). arm 2: Volunteers will be admitted, take dexamethasone at 22.00hrs, fast overnight, and take 20mg immediate release hydrocortisone with 200 millilitres of water on the morning of Day 1. Water will be allowed 1hr after the study drug, but no food for at least 4hrs post dose. Further dexamethasone doses will be given at 06:00, 12:00 and 18:00 hours on Day 1. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples) arm 3: Volunteers will be admitted, take dexamethasone at 22.00hrs, fast overnight, and take 20mg modified release hydrocortisone with 200millilitres of water on the morning of Day 1. Water will be allowed 1hr after the dose, but no food for at least 4hrs post dose. Further dexamethasone doses will be given at 06:00, 12:00, 18:00 and 22:00 hours on Day 1. One baseline pharmacokinetics (PK) sample will be taken prior to the dose, and then afterwards for over a 12 hour period (16 samples)

Interventions: intervention 1: Dexamethasone intervention 2: Chronocort: fasted intervention 3: Immediate release hydrocortisone: fasted intervention 4: Chronocort: fed
Intervention descriptions: intervention 1: Dexamethasone used to suppress endogenous cortisol secretion intervention 2: single dose of 20mg modified release hydrocortisone in the absence of food intervention 3: single dose of 20mg immediate release hydrocortisone in the absence of food intervention 4: single dose of 20mg modified release hydrocortisone in the presence of food

Protocol document: