An Investigational Study of Hydrocortisone

Condition(s) targeted: Adrenal Insufficiency

Intervention: Infacort (Drug); Hydrocortisone Tablet (Drug); i.v. Hydrocortisone Injection (Drug); Dexamethasone (Other)

Phase: Phase 1

Status: Completed

Sponsored by: Diurnal Limited

This study will investigate a new drug called Infacort®; a newly-developed immediate release formulation of a well-established drug called hydrocortisone. Hydrocortisone is used as a replacement treatment for people whose adrenal glands are not producing enough natural

cortisol - a condition known as adrenal insufficiency. The study will assess how Infacort®

acts once inside the body, by measuring cortisol and other hormone levels in the body, compared to already marketed hydrocortisone tablet and hydrocortisone intravenous (through the vein) injection. The population who are eligible to take part in the study are healthy male volunteers, aged between 18 and 60 years of age.

Official title: A Single Centre, Open Label, Partially Randomised, Single Dose, Crossover Study to Build a Model of Hydrocortisone Metabolism and Evaluate the Pharmacokinetics, Oral Bioavailability and Relationship to Metabolic Parameters of Hydrocortisone and Infacort® in Healthy Adult Male Volunteers.

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Primary outcome:

To determine the absolute bioavailability of cortisol from Infacort® Granules and Hydrocortisone Tablets using Intra-Venous (i.v) Hydrocortisone as the reference Injection.

To determine the comparative bioavailability of cortisol from Infacort® Granules with the reference Hydrocortisone Tablets.

Secondary outcome:

To assess the safety and tolerability of Infacort Granules and hydrocortisone throughout the study.

To evaluate the concentrations of cortisol binding protein and its relationship to calculated free cortisol and cortisol plasma/saliva ratios under physiological conditions and after the administration of dexamethasone and hydrocortisone.

To evaluate the normal physiology of cortisol and the relationship between cortisol and insulin sensitivity under physiological conditions and after administration of dexamethasone and Infacort®, Hydrocortisone Tablets and i.v Hydrocortisone.

To evaluate the pharmacokinetics (PK) and metabolism of cortisol under physiological conditions and after administration of dexamethasone and Infacort® Granules, Hydrocortisone Tablets and i.v Hydrocortisone Injection.

To explore the role of cortisol in regulation of metabolic pathways.

Detailed description: The study will evaluate the normal physiology, PK and metabolism of cortisol, investigate the PK and bioavailability of cortisol from the test Infacort® Granules (hydrocortisone) and the reference hydrocortisone tablets and i. v injection in healthy adult male volunteers and explore the role of cortisol in the regulation of metabolic pathways.

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Healthy male volunteers between 18 and 60 years of age, inclusive (at screening).

- Subjects with a Body Mass Index (BMI) of 21-28. Body Mass Index = Body weight (kg) /

(Height (m)2.

- Subjects with no clinically significant abnormal serum biochemistry, haematology and

urinalysis values within 14 days prior to Day 1 of Study Period 1.

- Subjects with a negative urinary drugs of abuse screen, determined within 14 days

prior to Day 1 of Study Period 1. A positive alcohol test may be repeated at the discretion of the Investigator.

- Subjects with negative HIV and Hepatitis B and C results.

- Subjects with no clinically significant abnormalities in 12-lead electrocardiogram

(ECG) determined within 14 days prior to Day 1 of Study Period 1.

- Subjects with 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 (IUD) + condom

- Diaphragm with spermicide + condom

- Subjects must be available to complete the study.

- Subjects must satisfy a medical examiner about their fitness to participate in 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 within 14 days prior to Day 1 of Study Period 1

(including high dose vitamins, dietary supplements or herbal remedies).

- Receipt of any vaccination within 14 days prior to Day 1 of Study Period 1.

- Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or

metabolic dysfunction.

- Presence of clinically significant infections (systemic fungal and viral infections,

acute bacterial infections).

- Current or previous history of tuberculosis.

- A clinically significant history of previous allergy / sensitivity to Hydrocortisone

and/or Dexamethasone.

- A clinically significant history or family history of psychiatric

disorders/illnesses.

- A clinically significant history of drug or alcohol abuse.

- Inability to communicate well with the Investigator (i. e., language problem, poor

mental development or impaired cerebral function).

- Participation in a New Chemical Entity clinical study within the previous 4 months or

a marketed drug clinical study within the previous 3 months. (N. B. The washout period between trials is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study)

- Subjects who have consumed more than 2 units of alcohol per day within seven (7) days

prior to Day 1 of Study Period 1or have consumed any alcohol within the 48 hour period prior to Day 1 of Study Period 1.

- Donation of 450ml or more of blood within the previous 3 months.

- Subjects who smoke (or ex-smokers who have smoked within 6 months prior to Day 1 of

Study Period 1).

- Subjects who work shifts (i. e. regularly alternate between days, afternoons and

nights).

Simbec Research Limited, Merthyr Tydfil CF48 4DR, United Kingdom

Volunteer Website

Starting date: October 2013
Last updated: January 6, 2014