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

Phase 1

Completed

• Conditions: Congenital Adrenal Hyperplasia; Adrenal Insufficiency
• Interventions: Drug: Hydrocortisone; Drug: Chronocort

• Registration Number: NCT03019614
• Lead Sponsor: Diurnal Limited

Brief Summary

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2010-03
• Primary Completion: 2010-04
• Study Completion: 2010-04
• Status Verified: 2017-01
• Study First Submitted: 2017-01-11
• Study First Submitted QC: 2017-01-11
• Last Update Submitted: 2017-01-11
• Study First Posted: 2017-01-12
• Last Update Posted: 2017-01-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Group 1	Chronocort	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.
Group 2	Chronocort	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.
Group 1	Hydrocortisone	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.

Primary Outcome Measures

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