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CompletedNCT03343327Updated Sep 14, 2026

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

A Phase 1 interventional study of Chronocort® and Cortef® in Adrenal Insufficiency, sponsored by Neurocrine UK Limited. Completed at 1 site in United Kingdom. Open to male participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-14.

Sponsored by Neurocrine UK Limited · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
25
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
Male
01

Study 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.

Read the detailed description

This study was an open-label, randomised, single dose, two-period, crossover study in 25 healthy male subjects.

The study comprised of a pre-study screen, followed by 2 treatment periods (1 and 2) and a post-study followup.

Screening (Day -28 to Day -1): Screening assessments were carried out within 28 days before first administration of IMP. Eligible subjects were asked to return for the treatment periods. Continued eligibility was confirmed pre-dose during each treatment period.

Treatment Periods (Day -1 to Day 1): Eligible subjects received a single-dose of each IMP over 2 treatment periods (1/period as determined by the randomisation schedule), each separated by 7 days washout. Each study period was approximately 2 days in duration, from the afternoon of Day -1 to the morning of Day 1 at 24 hours (h) post-dose. During each treatment period, Subjects arrived at the Clinical Unit on Day -1, IMP was administered on the morning of Day 0 fasted (following an overnight fast of at least 10 h) and subjects were discharged following the 24 h post-dose blood samples and completion of the scheduled measurements.

Pharmacokinetic (PK) samples were collected pre-dose at \~ -2min and up to 23 h post-dose (Day 1) (24 samples) for the measurement of cortisol. A further 3 baseline samples were taken for the measurement of cortisol. Safety was also evaluated throughout the study.

Post Study: After completion of both study periods, the subjects returned 4-22 days later for the final followup visit.

02

Conditions studied

  • Adrenal Insufficiency

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03

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Healthy male subjects between 18 and 45 years of age inclusive (at screening).
  2. A BMI of 18-30 kg/m2 (inclusive).
  3. No clinically significant abnormal serum biochemistry, haematology or urine examination values as defined by the Investigator.
  4. 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.
  5. Negative HIV and Hepatitis Band C results.
  6. No clinically significant abnormalities in 12-lead ECG as defined by the Investigator.
  7. No clinically significant deviation outside the normal ranges for blood pressure and heart rate measurements as defined by the Investigator.
  8. 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
  9. Subjects must be available to complete both periods of the study and the follow-up visit.
  10. Subjects must satisfy a medical examiner about their fitness to participate in the study.
  11. Subjects must be able to read and understand the informed consent form and must provide written informed consent to participate in the study.

Exclusion criteria

Exclusion Criteria:

  1. A clinically significant history of gastrointestinal disorder likely to influence drug absorption.
  2. 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).
  3. Evidence of renal. hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
  4. Receipt of any vaccination within the previous one month.
  5. Presence of infections (systemic fungal and viral infections, acute bacterial infections).
  6. Current or previous history of tuberculosis.
  7. A clinically significant history of previous allergy/sensitivity to hydrocortisone and/or dexamethasone.
  8. 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
  9. A clinically significant history of drug or alcohol abuse.
  10. Inability to communicate well with the Investigator (i.e., language problem, poor mental development or impaired cerebral function).
  11. 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).
  12. 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.
  13. Donation or receipt of 450 mL of blood within the previous three months.
  14. Subjects who smoke (or ex-smokers who have smoked within six months prior to first dose). This includes e-cigarette and shisha users.
  15. Subjects who work shifts (i.e. regularly alternate between days, afternoons and nights).
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    Chronocort®, then Cortef®

    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®

  • Active comparator
    Cortef®, then Chronocort®

    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

  • DrugChronocort®

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

  • DrugCortef®

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

05

What researchers measure

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.

    Time frame: 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

  1. Pharmacokinetic parameters for serum cortisol + relative bioavailability - Cmax

    The following PK endpoint was derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP. ◦ Cmax Maximum plasma cortisol concentration.

    Time frame: 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.

  2. Pharmacokinetic parameters for serum cortisol + relative bioavailability - Tmax

    The following PK endpoint was derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP. ◦ Tmax The time to maximum observed cortisol concentration sampled during a dosing interval.

    Time frame: 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.

  3. Pharmacokinetic parameters for serum cortisol + relative bioavailability - Kel

    The following PK endpoint was derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP. ◦ kel Elimination rate constant.

    Time frame: 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.

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

    The following PK endpoint was derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP. ◦ t1/2 Terminal half-life.

    Time frame: 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.

  5. Pharmacokinetic parameters for serum cortisol + relative bioavailability - AUC0-t

    The following PK endpoint was derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP. ◦ AUC0-t Area under the plasma cortisol concentration-time curve (AUC) from the time of dosing to the time of the last observed concentration.

    Time frame: 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.

  6. Pharmacokinetic parameters for serum cortisol - Serum cortisol clearance (CL/F)

    Calculated as Dose / AUC0-inf. This PK endpoint was derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP.

    Time frame: 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.

  7. Pharmacokinetic parameters for serum cortisol - Distribution during terminal elimination (Vz/F)

    Volume of distribution based on the terminal elimination phase following extravascular administration derived from baseline adjusted and unadjusted serum cortisol

    Time frame: 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.

  8. Observed changes in Safety Laboratory Data

    Observed changes in Safety Laboratory data (biochemistry, haematology \& urinalysis) during the course of the study, with any out of normal range values flagged.

    Time frame: Screening, Pre-dose and 10h and 24h post-dose during both treatment periods; Follow up

  9. Observed changes in Vital Signs

    Observed changes in vital signs data (blood pressure, pulse rate and oral temperature) during the course of the study, with any out of normal range values flagged.

    Time frame: Screening; Pre-dose and at 4 and 10h post-dose during both treatment periods; Follow up

  10. Observed changes in Electrocardiogram (ECG) data during the course of the study

    12-Lead ECG parameters (Heart Rate, PR interval, QRS width, QT interval, and QT interval corrected using Bazett's formula (QTcB)) and investigator clinical interpretation was listed with any out of normal range values flagged.

    Time frame: Screening, Pre-dose and 10h post-dose during both treatment periods; Follow up

  11. Adverse Events

    Adverse events (AEs) observed throughout the study

    Time frame: Through study completion - approximately 6 weeks

06

Study locations

1 site
  • Simbec Research Ltd.
    Merthyr Tydfil, CF48 4DR, United Kingdom
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03343327
Lead sponsor
Neurocrine UK Limited
Collaborators
Simbec Research, Brush Clinical Research Ltd., Voet Consulting, Bionical Emas Ltd., Medical Matters International Ltd
Responsible party
Sponsor
First posted
Nov 17, 2017
Start date
Feb 19, 2018
Primary completion
Apr 20, 2018
Completion
Apr 20, 2018
Last update
Sep 14, 2026

Study contacts

A Koch
principal investigator · Simbec Research

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
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