A Study of Infacort® Versus Cortef® in Healthy Adult Male and Female Subjects
A Study of Infacort® Versus Cortef® in Healthy Adult Male and Female Subjects
This was a two-part, single centre, open-label, randomised, single dose, two-period,
 crossover study to evaluate the bioavailability of Infacort® versus Cortef® immediate release
 hydrocortisone tablets in dexamethasone-suppressed healthy adult male and female subjects in
 the fasted and fed states.
The study was conducted in two parts (Part 1 and 2) which were not performed sequentially. In
 Part 1, 26 subjects were dosed in a fasted condition and in Part 2, 25 subjects were dosed in
 a fed condition. Each part comprised of a pre-study screen, followed by 2 treatment periods
 (1 and 2) and a post-study follow-up.

 Screening assessments (for Parts 1 and 2) were conducted within the 28 days before the first
 administration of a study intervention. Eligible participants were asked to return for the 2
 treatment periods. Continued eligibility was confirmed pre-dose for each treatment period.

 Part 1 (fasted state): Treatment Periods: Eligible participants received a single dose of
 each study intervention over 2 treatment periods (1 per treatment period). Each treatment
 period was approximately 1.5 days in duration. Participants arrived at the Clinical Unit on
 Day -1 and dexamethasone 1 mg was administrated at approximately 22:00 hours and then again
 at approximately 06:00 and 12:00 of Day 0 of each treatment period to suppress endogenous
 cortisol production. The study intervention was administered at approximately 08:00 on Day 0
 in the fasted state (after an overnight fast of at least 10 hours). Participants were
 discharged following the 12-hour post-dose blood sampling and consumption of a snack (Day 0).

 Part 2 (fed state): The same procedures were followed as for Part 1 except that study
 interventions were administered in a fed condition (30 minutes after the start of a
 standardised high-fat breakfast). PK samples in both study parts were collected pre-dose and
 up to 12 hours post-dose (19 samples for each treatment period) for measurement of cortisol
 levels. Safety was evaluated throughout the study. There was at least a 7-day washout period
 (up to a maximum of 14 days) between dose administrations. After completion of both study
 periods, participants were to return 7±2 days later for a final follow-up visit.
Inclusion Criteria:

 1. Healthy males and females between 18 and 55 years of age, inclusive (at screening).

 2. A body mass index (BMI) of 18 to 30 kg/m2 (inclusive)

 3. No clinically significant abnormal serum biochemistry, haematology or urine
 examination values, as defined by the Investigator.

 4. A negative urinary drugs of abuse screen. A positive alcohol test or drugs of abuse
 test could be repeated at the discretion of the Investigator.

 5. Negative human immunodeficiency virus (HIV) and hepatitis B and C test results.

 6. No clinically significant abnormalities in the 12-lead ECG, as defined by the
 Investigator.

 7. No clinically significant deviation outside of the normal ranges for blood pressure
 and heart rate measurements, as defined by the Investigator.

 8. Male participants (unless anatomically sterile or abstinence from sexual intercourse
 was in line with preferred and usual lifestyle) and sexual partners were to use an
 effective contraception method during the study and for 3 months after the last
 intervention, for example:

 -  Established use of oral, injected or implanted hormonal contraceptive.

 -  Intrauterine device or intrauterine system.

 -  Condom and diaphragm with spermicide.

 9. Female participants of childbearing potential (unless abstinence from sexual
 intercourse was in line with preferred and usual lifestyle) with a negative pregnancy
 test at screening and on admission, and willing to use an effective method of
 contraception from the first dose until 3 months after the last intervention, for
 example:

 -  Established use of oral / injected / implanted hormonal methods of contraception.

 -  Intrauterine device or intrauterine system.

 -  Barrier methods: condom + occlusive cap (diaphragm or cervical/vault caps) with
 spermicidal foam/gel/film/cream/suppository.

 10. Female participants of non-childbearing potential with negative pregnancy test at
 screening. For the purposes of the study, non-childbearing was defined as being
 amenorrhoeic for at least 12 consecutive months or at least 4 months post-surgical
 sterilisation (including bilateral fallopian tube ligation or bilateral oophorectomy
 with or without hysterectomy). Menopausal status was confirmed at screening by
 demonstrating that levels of follicle stimulating hormone (FSH) fell within the
 respective reference range. In the event a participant's menopausal status had been
 clearly established (for example, the participant indicated she had been amenorrhoeic
 for 10 years) but FSH levels were not consistent with a post-menopausal condition,
 determination of eligibility was at the Investigator's discretion following
 consultation with the Sponsor.

 11. Participants were available to complete both study periods and the follow-up visit.

 12. Participants satisfied a medical examiner that they were fit to participate in the
 study.

 13. Participants were able to read and understand the ICF and provide written informed
 consent to take part in the study.

 Exclusion Criteria:

 1. A clinically significant history of gastrointestinal disorder likely to influence drug
 absorption.

 2. Receipt of any medication other than acetaminophen within the 14 days prior to dosing
 (including topical steroids, vitamins, dietary supplements or herbal remedies).

 3. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or
 metabolic dysfunction.

 4. Receipt of any vaccination within the previous one month.

 5. Presence of infections (systemic fungal and viral infections, acute bacterial
 infections).

 6. Current or previous history of tuberculosis.

 7. A clinically significant history of previous allergy/sensitivity to hydrocortisone
 and/or dexamethasone.

 8. Meeting any of the contraindications for Cortef® and/or dexamethasone, as detailed in
 the USPI and Summary of Product Characteristics (SmPC).

 9. A clinically significant history of drug or alcohol abuse.

 10. Inability to communicate well with the Investigator (i.e. language problem, poor
 mental development or impaired cerebral function).

 11. Participation in a New Chemical Entity or marketed drug clinical study within the
 previous 3 months or, five half-lives of 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).

 12. Participants who had consumed more than 2 units of alcohol per day within the 7 days
 prior to the first dose or had consumed any alcohol within the 48-hour period prior to
 the first dose.

 13. Donation or receipt of equal to or greater than 450 mL of blood within the previous
 three months.

 14. Participants who smoked (or ex-smokers who had smoked within the 6 months prior to the
 first dose). This included e-cigarette and shisha users.

 15. Participants who worked shifts (i.e. regularly alternated between days, afternoons and
 nights).

 16. Vegetarians, vegans or those with other dietary restrictions which meant they were
 unable to consume the standardised high-fat breakfast (applicable to Part 2 only).