A Study of Chronocort® Versus Cortef ® in Healthy Adult Male Subjects

NCT03343327 | Completed Phase 1 FDA Drug

• 1 other identifier: DIUR-008
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This was a single centre, open label, randomised, two period, crossover study to evaluate the bioavailability of Chronocort® versus Cortef® immediate release hydrocortisone tablets in dexamethasone-suppressed healthy adult male subjects.

Conditions

Adrenal Insufficiency

Outcome Measures

Primary Outcomes (1)

• Area under the concentration time curve from time 0 to infinity (AUC0-inf) of Chronocort® to Cortef® based on baseline adjusted and unadjusted serum cortisol concentration calculated for each sampling time point.

  Comparing the area under the concentration time curve of Chronocort® compared to Cortef® immediate release hydrocortisone tablets.

  Samples taken at 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 11,12, 13, 14, 16, 18, 20, 22, and 24 hours (morning of Day 1) in both periods.

Secondary Outcomes (11)

• Pharmacokinetic parameters for serum cortisol + relative bioavailability - Cmax

  Samples taken at 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 11,12, 13, 14, 16, 18, 20, 22, and 24 hours (morning of Day 1) in both periods.

• Pharmacokinetic parameters for serum cortisol + relative bioavailability - Tmax

  Samples taken at 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 11,12, 13, 14, 16, 18, 20, 22, and 24 hours (morning of Day 1) in both periods.

• Pharmacokinetic parameters for serum cortisol + relative bioavailability - Kel

  Samples taken at 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 11,12, 13, 14, 16, 18, 20, 22, and 24 hours (morning of Day 1) in both periods.

• Pharmacokinetic parameters for serum cortisol + relative bioavailability - t1/2

  Samples taken at 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 11,12, 13, 14, 16, 18, 20, 22, and 24 hours (morning of Day 1) in both periods.

• Pharmacokinetic parameters for serum cortisol + relative bioavailability - AUC0-t

  Samples taken at 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 11,12, 13, 14, 16, 18, 20, 22, and 24 hours (morning of Day 1) in both periods.

Study Arms (2)

Chronocort®, then Cortef®

EXPERIMENTAL

Single dose of 20mg Chronocort® (oral administration), followed by a single dose of 20mg Cortef® Immediate Release Hydrocortisone Tablets (oral administration).

Drug: Chronocort®; Drug: Cortef®

Cortef®, then Chronocort®

ACTIVE COMPARATOR

Single dose of 20mg Cortef® Immediate Release Hydrocortisone Tablets (oral administration), followed by a single dose of 20mg Chronocort® (oral administration).

Drug: Chronocort®; Drug: Cortef®

Interventions

Chronocort® DRUG

Single dose of 20mg Chronocort® administered in one treatment period

Chronocort®, then Cortef®; Cortef®, then Chronocort®

Cortef® DRUG

Single dose of 20mg Cortef® administered in one treatment period

Chronocort®, then Cortef®; Cortef®, then Chronocort®

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects between 18 and 45 years of age inclusive (at screening).
• A BMI of 18-30 kg/m2 (inclusive).
• No clinically significant abnormal serum biochemistry, haematology or urine examination values as defined by the Investigator.
• A negative urinary drugs of abuse screen. A positive alcohol test or drugs of abuse test may be repeated at the discretion of the Investigator.
• Negative HIV and Hepatitis Band C results.
• No clinically significant abnormalities in 12-lead ECG as defined by the Investigator.
• No clinically significant deviation outside the normal ranges for blood pressure and heart rate measurements as defined by the Investigator.
• Subjects (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) and sexual partners must use 2 effective contraception methods during the trial and for 3 months after the last dose, for example:
• Oral, injected or implanted hormonal contraceptive+ condom
• Intra-uterine device (IUD) + condom
• Diaphragm with spermicide + condom
• Subjects must be available to complete both periods of the study and the follow-up visit.
• Subjects must satisfy a medical examiner about their fitness to participate in the study.
• Subjects must be able to read and understand the informed consent form and must provide written informed consent to participate in the study.

You may not qualify if:

• A clinically significant history of gastrointestinal disorder likely to influence drug absorption.
• Receipt of any medication with the exception of paracetamol within the 14 days prior to dosing (including topical steroids, vitamins, dietary supplements or herbal remedies).
• Evidence of renal. hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
• Receipt of any vaccination within the previous one month.
• Presence of 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.
• Meeting any of the contraindications for Cortef® and/or dexamethasone, as detailed in the United States Prescribing Information (USPI)/Summary of Product Characteristics (SmPC), respectively
• 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 or a marketed drug clinical study within the previous three months, or five half- lives of the 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).
• Subjects who have consumed more than two units of alcohol per day within seven days prior to the first dose or have consumed any alcohol within the 48-hour period prior to the first dose.
• Donation or receipt of 450 mL of blood within the previous three months.
• Subjects who smoke (or ex-smokers who have smoked within six months prior to first dose). This includes e-cigarette and shisha users.
• Subjects who work shifts (i.e. regularly alternate between days, afternoons and nights).

Sponsors & Collaborators

• Neurocrine UK Limited: lead
• Simbec Research: collaborator
• Brush Clinical Research Ltd.: collaborator
• Voet Consulting: collaborator
• Bionical Emas Ltd.: collaborator
• Medical Matters International Ltd: collaborator

Study Sites (1)

Simbec Research Ltd.

Merthyr Tydfil, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Adrenal Insufficiency

Interventions

Hydrocortisone

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• A Koch

  Simbec Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2017
• First Posted: November 17, 2017
• Study Start: February 19, 2018
• Primary Completion: April 20, 2018
• Study Completion: April 20, 2018
• Last Updated: June 19, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)