A Study of Infacort® Versus Cortef® in Healthy Adult Male and Female Subjects

• Status: Completed
• Trial end date: 2018-07-13
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Diurnal Limited
• Collaborators: Bionical-Emas Pharma Ltd; Brush Clinical Research Ltd.; Emas Pharma Ltd.; Medical Matters International Ltd.; Nichol Pharma Services Ltd.; Simbec Research; Voet Consulting
• Treatments: Cortisol succinate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate

Criteria

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).