Clinical trial NCT02408068: Effect of Slow Release Hydrocortisone on Fed & Fasting Volunteers; Immediate Release on Fasting Only
Official title: Open Label Randomised 3 Period Crossover Study to Evaluate Bioavailability of Modified Release Hydrocortisone (HC) Under Fasting & Fed Conditions & Immediate Release HC Tablets Under Fasting Conditions in Dexamethasone-suppressed Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: subjects
Lead sponsor: Neurocrine UK Limited
Sponsor class: INDUSTRY
Collaborators: name: Simbec Research
First posted: 2015-04-03
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: Inclusion Criteria:

* Healthy male volunteers between 18 and 60 years of age, inclusive (at screening)
* A body mass index of 21-28 (inclusive).
* No clinically significant abnormal serum biochemistry, haematology and urine examination values
* A negative urinary drugs of abuse screen. A positive alcohol test may be repeated at the discretion of the investigator.
* Negative Human Immunodeficiency Virus (HIV) and Hepatitis b \& C results
* No clinically significant abnormalities in 12-lead Electrocardiogram (ECG)
* No clinically significant deviation outside the normal ranges for blood pressure and pulse measurements
* Subjects (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) and sexual partners must use effective contraception methods during the trial and for 3 months after the last dose, for example:

  * Oral contraceptive + condom
  * Intra-uterine device + condom
  * Diaphragm with spermicide + condom
* Subjects must be available to complete the study
* Subjects must provide written informed consent to participate in the study

Exclusion Criteria:

* A clinically significant history of gastrointestinal disorder likely to influence drug absorption
* Receipt of regular medication (including high dose vitamins, dietary supplements or herbal remedies)
* Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction Receipt of any vaccination within the previous one month
* Presence of clinically significant infections (systemic fungal and viral infections, acute bacterial infections)
* Current of previous history of tuberculosis
* A clinically significant history of previous allergy/sensitivity to hydrocortisone and/or dexamethasone
* A clinically significant history of family history of psychiatric disorders/illnesses
* A clinically significant history of drug or alcohol abuse
* Inability to communicate well with the investigator (ie language problem, poor mental development or impaired cerebral function)
* Participation in a New Chemical entity clinical study within the previous four months or a marketed drug clinical study within the previous three months
* Subjects who have consumed more than two units of alcohol pre day within seven days prior to the first dose or have consumed any alcohol within the 48hr period prior to the first dose
* Donation of greater than or equal to 450ml blood within the previous three months
* Subjects who smoke or ex-smokers who have smoked within six months prior to first dose
* Subjects who work shifts (ie regularly alternate between days, afternoons and nights)

Primary outcomes:
measure: Chronocort Cmax
timeFrame: 24 hours
measure: Comparison of Fed and Fasted Chronocort AUC0-t
timeFrame: 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.)
measure: Comparison of Fed and Fasted Chronocort Tmax
timeFrame: 24 hours
measure: Bioavailability of Chronocort® vs Hydrocortisone Tablets - Cmax
timeFrame: 24 hours
measure: Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using AUC0-t
timeFrame: 24 hours
measure: Bioavailability of Chronocort® vs Hydrocortisone Tablets - Fasted Using Tmax.
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
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