A Study of Chronocort® Versus Cortef ® in Healthy Adult Male Subjects

This study was an open-label, randomised, single dose, two-period, crossover study in 25 healthy male subjects.

The study comprised of a pre-study screen, followed by 2 treatment periods (1 and 2) and a post-study followup.

Screening (Day -28 to Day -1): Screening assessments were carried out within 28 days before first administration of IMP. Eligible subjects were asked to return for the treatment periods. Continued eligibility was confirmed pre-dose during each treatment period.

Treatment Periods (Day -1 to Day 1): Eligible subjects received a single-dose of each IMP over 2 treatment periods (1/period as determined by the randomisation schedule), each separated by 7 days washout. Each study period was approximately 2 days in duration, from the afternoon of Day -1 to the morning of Day 1 at 24 hours (h) post-dose. During each treatment period, Subjects arrived at the Clinical Unit on Day -1, IMP was administered on the morning of Day 0 fasted (following an overnight fast of at least 10 h) and subjects were discharged following the 24 h post-dose blood samples and completion of the scheduled measurements.

Pharmacokinetic (PK) samples were collected pre-dose at ~ -2min and up to 23 h post-dose (Day 1) (24 samples) for the measurement of cortisol. A further 3 baseline samples were taken for the measurement of cortisol. Safety was also evaluated throughout the study.

Post Study: After completion of both study periods, the subjects returned 4-22 days later for the final followup visit.

Inclusion criteria

• Healthy male subjects between 18 and 45 years of age inclusive (at screening).
• A BMI of 18-30 kg/m2 (inclusive).
• No clinically significant abnormal serum biochemistry, haematology or urine examination values as defined by the Investigator.
• A negative urinary drugs of abuse screen. A positive alcohol test or drugs of abuse test may be repeated at the discretion of the Investigator.
• Negative HIV and Hepatitis Band C results.
• No clinically significant abnormalities in 12-lead ECG as defined by the Investigator.
• No clinically significant deviation outside the normal ranges for blood pressure and heart rate measurements as defined by the Investigator.
• 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 2 effective contraception methods during the trial and for 3 months after the last dose, for example:

• Oral, injected or implanted hormonal contraceptive+ condom
• Intra-uterine device (IUD) + condom
• Diaphragm with spermicide + condom
• Subjects must be available to complete both periods of the study and the follow-up visit.
• Subjects must satisfy a medical examiner about their fitness to participate in the study.
• Subjects must be able to read and understand the informed consent form and 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 any medication with the exception of paracetamol within the 14 days prior to dosing (including topical steroids, 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 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.
• Meeting any of the contraindications for Cortef® and/or dexamethasone, as detailed in the United States Prescribing Information (USPI)/Summary of Product Characteristics (SmPC), respectively
• 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 or a marketed drug clinical study within the previous three months, or five half- lives of the study drug, whichever is the longer period. (NB. the three-month 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 two units of alcohol per day within seven days prior to the first dose or have consumed any alcohol within the 48-hour period prior to the first dose.
• Donation or receipt of 450 mL of blood within the previous three months.
• Subjects who smoke (or ex-smokers who have smoked within six months prior to first dose). This includes e-cigarette and shisha users.
• Subjects who work shifts (i.e. regularly alternate between days, afternoons and nights).