Comparison of Pharmacokinetics of Infacort® Versus Immediate-release Hydrocortisone

Study Overview
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Brief Summary
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This was a single centre, open-label, randomised, 5-way crossover study.

Detailed Description
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This was a single centre, open-label, randomised, 5-way crossover study design to compare the PK of Infacort® versus immediate-release hydrocortisone tablets and to evaluate the dose proportionality of 0.5 mg, 2 mg, 5 mg and 10 mg Infacort®. The study was conducted in 1 cohort of 16 healthy male subjects and comprised a Screening Visit, 5 treatment periods (Treatment Periods 1 to 5) and a Post-study Visit.

Official Title
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A Single Centre, Open Label, Randomised, Crossover Study in Dexamethasone-suppressed Healthy Adult Male Volunteers to Compare the Pharmacokinetics of Infacort® Versus Immediate-release Hydrocortisone Tablets at a Single Dose of 10 mg and to Evaluate the Dose Proportionality of Infacort® at Doses of 0.5 mg, 2 mg, 5 mg and 10 mg

Conditions
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Healthy Subjects

Intervention / Treatment
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* Drug: Infacort
* Drug: Hydrocortisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers between 18 and 60 years of age, inclusive (at Screening Visit). Subjects with a Body Mass Index (BMI) of 21-28. Subjects with no clinically significant abnormal serum biochemistry, haematology and urine examination values within 14 days prior to the first dose of investigational medicinal product (IMP). Subjects with a negative urinary drugs of abuse screen determined within 14 days prior to the first dose of IMP. A positive alcohol test may have been repeated at the discretion of the Investigator. Subjects with negative human immunodeficiency virus (HIV) and hepatitis B surface antigen (Hep B) and hepatitis C virus antibody (Hep C) results. Subjects with no clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined within 14 days prior to the first dose of IMP. 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 was in-line with the preferred and usual lifestyle of the subject) and sexual partners used effective contraception methods during the trial and for 3 months after the last dose of IMP, for example; oral contraceptive + condom, intra-uterine device (IUD) + condom or diaphragm with spermicide + condom. Subjects were available to complete the study. Subjects satisfied a medical examiner about their fitness to participate in the study. Subjects provided 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 the first dose of IMP (including high dose vitamins, dietary supplements or herbal remedies). Receipt of any vaccination within 14 days prior to the first dose of IMP. 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). Participated 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 was 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 had consumed more than 2 units of alcohol per day within 7 days prior to the first dose of IMP or had consumed any alcohol within the 48 hr period prior to the first dose of IMP. Donation of 450 mL or more of blood within the previous 3 months. Subjects who smoked (or ex-smokers who had smoked within 6 months prior to first dose of IMP). Subjects who worked shifts (i.e. regularly alternated between days, afternoons and nights).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infacort 0.5 mg<br>Multi-particulate granules from 1 (0.5 mg) capsule | Drug: Infacort<br>* Multi-particulate granules<br>|
| Experimental: Infacort 2 mg<br>Multi-particulate granules from 1 (2 mg) capsule | Drug: Infacort<br>* Multi-particulate granules<br>|
| Experimental: Infacort 5 mg<br>Multi-particulate granules from 1 (5 mg) capsule | Drug: Infacort<br>* Multi-particulate granules<br>|
| Experimental: Infacort 10 mg<br>Multi-particulate granules from 1 (10 mg) capsule | Drug: Infacort<br>* Multi-particulate granules<br>|
| Active Comparator: Hydrocortisone<br>1 (10 mg) tablet | Drug: Hydrocortisone<br>* Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of Infacort vs Hydrocortisone | To compare the Cmax of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg. | -1h, -0.5h, 0h, 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 | 
| Time to Reach the Maximum Plasma Concentration (Tmax) of Infacort vs Hydrocortisone | To compare the Tmax of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg. | -1h, -0.5h, 0h, 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 | 
| Area Under the Curve (AUC0-t) of Infacort vs Hydrocortisone | To compare the AUC0-t of Infacort® versus immediate-release hydrocortisone in a single dose of 10 mg. AUC0-t represents the total exposure to drug over time, hence the reporting of a single value below. | -1h, -0.5h, 0h, 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg | To determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg and 10 mg. | -1h, -0.5h, 0h, 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 | 
| Time to Maximum Plasma Concentration (Tmax) of Infacort at Doses of 0.5, 2, 5 and 10 mg | To determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg and 10 mg. | -1h, -0.5h, 0h, 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 | 
| Area Under the Curve (AUC0-t) of Infacort at Doses of 0.5, 2, 5 and 10 mg | To determine the dose proportionality for Infacort® at doses of 0.5 mg, 2 mg, 5 mg and 10 mg. | 1 day | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) as Assessed by Medical Dictionary for Regulatory Activities (MedDRA) Dictionary, Version 16.0. | To assess the safety and tolerability of Infacort® throughout the study. For a full list of TEAEs per arm, please refer to the Adverse Events section. | 1 day |