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

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

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).

Study Overview

• Status: Completed
• Conditions: Congenital Adrenal Hyperplasia; Adrenal Insufficiency
• Intervention / Treatment: Drug: Chronocort; Drug: Hydrocortisone

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group 1; 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: Chronocort; Modified formulation of hydrocortisone; Drug: Hydrocortisone; Generic hydrocortisone
EXPERIMENTAL: Group 2; 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; Modified formulation of hydrocortisone

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Diurnal Limited
• Collaborators: Simbec Research
• Investigators: Principal Investigator: Salvatore Febbraro, Simbec Research

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (ACTUAL): April 1, 2010
• Study Completion (ACTUAL): April 1, 2010

Study Registration Dates

• First Submitted: January 11, 2017
• First Submitted That Met QC Criteria: January 11, 2017
• First Posted (ESTIMATE): January 12, 2017

Study Record Updates

• Last Update Posted (ESTIMATE): January 12, 2017
• Last Update Submitted That Met QC Criteria: January 11, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Adrenal Gland Diseases; Steroid Metabolism, Inborn Errors; Hyperplasia; Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenal Insufficiency; Anti-Inflammatory Agents; Hydrocortisone
• Other Study ID Numbers: DIUR-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO