Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03343327
Recruitment Status : Completed
First Posted : November 17, 2017
Last Update Posted : April 26, 2018
Sponsor:
Collaborators:
Simbec Research
Brush Clinical Research Ltd.
Voet Consulting
EMAS Pharma
Medical Matters International Ltd.
Information provided by (Responsible Party):
Diurnal Limited

Brief Summary:
This is 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.

Condition or disease Intervention/treatment Phase
Adrenal Insufficiency Drug: Chronocort® Drug: Cortef® Phase 1

Detailed Description:

This study is an open-label, randomised, single dose, two-period, crossover study in 24 healthy male subjects.

The study will comprise 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 will be carried out within 28 days before first administration of IMP. Eligible subjects will be asked to return for the treatment periods. Continued eligibility will be confirmed pre-dose during each treatment period.

Treatment Periods (Day -1 to Day 1): Eligible subjects will receive a single-dose of each IMP over 2 treatment periods (1/period as determined by the randomisation schedule), each separated by at least 7 days washout. Each study period will be 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 will arrive at the Clinical Unit on Day -1, IMP will be administered on the morning of Day 0 fasted (following an overnight fast of at least 10 h) and subjects will be discharged following the 24 h post-dose blood samples and completion of the scheduled measurements.

Pharmacokinetic (PK) samples will be 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 will be taken for the measurement of cortisol. Safety will also be evaluated throughout the study.

Post Study: After completion of both study periods, the subjects will return 7 ± 2 days later for the final followup visit.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Centre, Open-label, Randomised, Single Dose, Two Period, Crossover Relative Bioavailability Study of Chronocort® Versus Cortef® Immediate Release Hydrocortisone Tablets in Dexamethasone-suppressed Healthy Adult Male Subjects.
Actual Study Start Date : February 19, 2018
Actual Primary Completion Date : April 20, 2018
Actual Study Completion Date : April 20, 2018


Arm Intervention/treatment
Experimental: Chronocort®
Single dose of 20mg Chronocort®
Drug: Chronocort®
Single dose of 20mg Chronocort® administered in one treatment period

Active Comparator: Cortef®
Single dose of 20mg Cortef® Immediate Release Hydrocortisone Tablets
Drug: Cortef®
Single dose of 20mg Cortef® administered in one treatment period




Primary Outcome Measures :
  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. [ 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. ]
    Comparing the area under the concentration time curve of Chronocort® compared to Cortef® immediate release hydrocortisone tablets.


Secondary Outcome Measures :
  1. Pharmacokinetic parameters for serum cortisol + relative bioavailability [ 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. ]

    The following PK endpoint will be derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP.

    ◦ Cmax Maximum plasma cortisol concentration.


  2. Pharmacokinetic parameters for serum cortisol + relative bioavailability [ 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. ]

    The following PK endpoint will be 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.


  3. Pharmacokinetic parameters for serum cortisol + relative bioavailability [ 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. ]

    The following PK endpoint will be derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP.

    ◦ kel Elimination rate constant.


  4. Pharmacokinetic parameters for serum cortisol + relative bioavailability [ 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. ]

    The following PK endpoint will be derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP.

    ◦ t1/2 Terminal half-life.


  5. Pharmacokinetic parameters for serum cortisol + relative bioavailability [ 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. ]

    The following PK endpoint will be 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, regardless of whether or not the last concentration is measurable.


  6. Pharmacokinetic parameters for serum cortisol + relative bioavailability [ 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. ]

    The following PK endpoint will be derived from baseline adjusted and unadjusted serum cortisol concentration-time data following administration of each IMP.

    ◦ AUC0-inf The area under the curve (AUC) extrapolated to infinity from dosing time, based on the last observed concentration.


  7. Observed changes in Electrocardiogram (ECG) data during the course of the study [ Time Frame: Screening, Study Periods 1 & 2, Follow up ]
    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 will be listed with any out of normal range values flagged. Descriptive statistics (N, n, mean, SD, minimum, median and maximum) of absolute and change from baseline (Day 0 pre-dose) values at each time-point will be tabulated.

  8. Routine Biochemistry Laboratory Safety Data [ Time Frame: Through study completion - approximately 6 weeks ]
    Biochemistry parameters will be listed with any out of normal range values flagged. Laboratory test results which are out of normal range will also be presented separately along with normal reference ranges. Descriptive statistics of biochemistry parameters (N, n, mean, SD, minimum, median and maximum) of absolute and change from baseline (Day -1) values at each time-point will be tabulated.

  9. Routine Haematology Laboratory Safety Data [ Time Frame: Through study completion - approximately 6 weeks ]
    Haematology parameters will be listed with any out of normal range values flagged. Laboratory test results which are out of normal range will also be presented separately along with normal reference ranges. Descriptive statistics of haematology parameters (N, n, mean, SD, minimum, median and maximum) of absolute and change from baseline (Day -1) values at each time-point will be tabulated.

  10. Routine Urinalysis Laboratory Safety Data [ Time Frame: Through study completion - approximately 6 weeks ]
    Urinalysis parameters will be listed with any out of normal range values flagged. Laboratory test results which are out of normal range will also be presented separately along with normal reference ranges.

  11. Adverse Events [ Time Frame: Through study completion - approximately 6 weeks ]
    Adverse events (AEs) observed throughout the study

  12. Vital Signs Data [ Time Frame: Screening; Pre-dose and at 4 and 10h post dose during both treatment periods; Follow up ]

    Vital signs parameters will be listed with any out of normal range values flagged.

    Descriptive statistics (N, n, mean, SD, minimum, median and maximum) of absolute and change from baseline (Day 0 pre-dose) values at each time-point will be tabulated.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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 (please refer to Appendix 1 for normal ranges).
  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:

  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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03343327


Locations
Layout table for location information
United Kingdom
Simbec Research Ltd.
Merthyr Tydfil, United Kingdom, CF48 4DR
Sponsors and Collaborators
Diurnal Limited
Simbec Research
Brush Clinical Research Ltd.
Voet Consulting
EMAS Pharma
Medical Matters International Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Annelize Koch Simbec Research

Layout table for additonal information
Responsible Party: Diurnal Limited
ClinicalTrials.gov Identifier: NCT03343327    
Other Study ID Numbers: DIUR-008
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: April 26, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Adrenal Insufficiency
Adrenal Gland Diseases
Endocrine System Diseases
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone hemisuccinate
Anti-Inflammatory Agents