An Open Label Study in Healthy Volunteers to Compare Chronocort® to Hydrocortisone

Study Overview
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Brief Summary
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This was an open label, randomized, single dose, three period crossover pharmacokinetic study of Chronocort® in 30 healthy male volunteers. The study was conducted in smaller sub groups (Group 1, n=18 and Group 2, n=12).

Official Title
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An Open Label, Randomised, Single Dose, 3-period Crossover Study in Healthy Volunteers to: a) Compare the Pharmacokinetics of Chronocort® Formulations Versus Immediate Release Hydrocortisone, and (b) Determine the Dose Proportionality of Chronocort® Formulations

Conditions
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Congenital Adrenal Hyperplasia, Adrenal Insufficiency

Intervention / Treatment
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* Drug: Hydrocortisone
* Drug: Chronocort


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). 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 urine examination values within 14 days of the start of the study. The parameters measured included those shown in Appendix 3 of the Study Protocol. Subjects with a negative urinary drugs of abuse screen (including alcohol), determined within 14 days of the start of the study. 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 of the start of the study. Subjects with no clinically-significant deviation outside the normal ranges for blood pressure and pulse measurements. Subjects and sexual partners must have used 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 spermacide + condom Subjects must have been available to complete the study. Subjects must have satisfied a medical examiner about their fitness to participate in the study. Subjects must have 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 of the first study day (including high dose vitamins, dietary supplements or herbal remedies). Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction. A clinically significant history of previous allergy / sensitivity to Hydrocortisone. 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 16 weeks or a marketed drug clinical study within the previous 12 weeks. Subjects who had consumed more than 2 units of alcohol per day within seven (7) days prior to the first dose or had consumed any alcohol within the 48 hour period prior to the first dose. Donation of 450ml or more blood within the previous 12 weeks. 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Volunteers in group 1 received the following interventions: Chronocort® 30 mg given at night (  23:00h) as a combination of one 10mg capsule and one 20mg capsule (n=18). Chronocort® 30mg given as one 20mg capsule at night (  23:00h) and as one 10mg capsule in the morning (  7:00h) following the initial night-time dose (n=18). Hydrocortisone 30mg given at night (  23:00h) given as three 10mg tablets (n=18). Each administration of IMP was separated by a washout period of at least 7 days. | Drug: Hydrocortisone<br>* Generic hydrocortisone<br>Drug: Chronocort<br>* Modified formulation of hydrocortisone<br>|
| Experimental: Group 2<br>Volunteers in group 2 received the following interventions: Chronocort® 5mg given at night (  23:00h) as one 5mg capsule (n=12). Chronocort® 10mg given at night (  23:00h) as one 10mg capsule (n=12). Chronocort® 20mg given at night (  23:00h) as one 20mg capsule (n=12). Each administration of IMP was separated by a washout period of at least 7 days. | Drug: Chronocort<br>* Modified formulation of hydrocortisone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Derived pharmacokinetic parameter: Tmax | Tmax measures the time at which Cmax - maximum serum concentration - is observed | 24 hours | 
| Derived pharmacokinetic parameter: Tlag | Tlag measures the delay between dosing and being able to observe the drug/metabolite within the sampling area (e.g., blood serum) | 24 hours | 
| Derived pharmacokinetic parameter: Cmax | Cmax measures the time taken for the drug/metabolite to reach maximum serum concentration | 24 hours | 
| Derived pharmacokinetic parameter: AUC(0 - t) (Area under the curve) | Area under the serum concentration versus time curve from time | 24 hours | 
| Derived pharmacokinetic parameter: AUC(0-∞)(Area under the curve) | Area under the serum concentration versus time curve from time = 0h extrapolated to infinity | 24 hours | 
| Derived pharmacokinetic parameter: CL | Time to drug clearance | 24 hours | 
| Derived pharmacokinetic parameter: T1/2 | Time required to reach 1/2 Cmax | 24 hours |