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An Investigational Study of Hydrocortisone

Primary Purpose

Adrenal Insufficiency

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Hydrocortisone granules

Hydrocortisone Tablet

i.v. Hydrocortisone Injection

Dexamethasone

About this trial

This is an interventional other trial for Adrenal Insufficiency

Eligibility Criteria

18 Years - 60 Years (Adult)MaleAccepts Healthy Volunteers

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 urinalysis values within 14 days prior to Day 1 of Study Period 1.
Subjects with a negative urinary drugs of abuse screen, determined within 14 days prior to Day 1 of Study Period 1. A positive alcohol test may be repeated at the discretion of the Investigator.
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 prior to Day 1 of Study Period 1.
Subjects with no clinically-significant deviation outside the normal ranges for blood pressure and pulse measurements.
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 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 spermicide + condom
Subjects must be available to complete the study.
Subjects must satisfy a medical examiner about their fitness to participate in the study.
Subjects must provide 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 prior to Day 1 of Study Period 1 (including high dose vitamins, dietary supplements or herbal remedies).
Receipt of any vaccination within 14 days prior to Day 1 of Study Period 1.
Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction.
Presence of clinically significant 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.
A clinically significant history or family history of psychiatric disorders/illnesses.
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 4 months or a marketed drug clinical study within the previous 3 months. (N.B. The 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 2 units of alcohol per day within seven (7) days prior to Day 1 of Study Period 1or have consumed any alcohol within the 48 hour period prior to Day 1 of Study Period 1.
Donation of 450ml or more of blood within the previous 3 months.
Subjects who smoke (or ex-smokers who have smoked within 6 months prior to Day 1 of Study Period 1).
Subjects who work shifts (i.e. regularly alternate between days, afternoons and nights).

Sites / Locations

Simbec Research Limited

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

No Intervention

Other

Experimental

Active Comparator

Arm Label

Endogenous Cortisol

Dexamethasone

Infacort®

Hydrocortisone Tablet

i.v Hydrocortisone Injection

Arm Description

No Study medication will be given during this study period, however various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points.

1mg Dexamethasone will be administered at 22:00 on Day 1 and at 06:00 and 12:00 on Day 2. Various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points. Dexamethasone is considered a challenge agent and therefore a non-IMP

20mg Infacort® will be administered on Day 2 at 07:00. Dexamethasone is a challenge agent and will be taken to suppress endogenous adrenocorticotropic Hormone (ACTH) and cortisol. 1mg Dexamethasone will be administered at 22:00 on Day 1 and 06:00 and 12:00 on Day 2. Various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points.

20mg Hydrocortisone Tablet will be administered on Day 2 at 07:00. Dexamethasone is a challenge agent and will be taken to suppress endogenous ACTH and Cortisol. 1mg Dexamethasone will be administered at 22:00 on Day 1 and 06:00 and 12:00 on Day 2. Various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points.

20mg i.v. Hydrocortisone Injection will be administered on Day 2 at 07:00. Dexamethasone is a challenge agent and will be taken to suppress endogenous ACTH and Cortisol. 1mg Dexamethasone will be administered at 22:00 on Day 1 and 06:00 and 12:00 on Day 2. Various blood, urine and saliva samples will be taken in order to measure normal levels of hormones and other chemicals at several time-points.

Outcomes

Primary Outcome Measures

Maximum Serum Concentration (Cmax)

Derived PK for Serum Cortisol: Maximum serum concentration (Cmax)

AUC0-t

Derived PK for Serum Cortisol: Area under the curve from 0-24 hours

Secondary Outcome Measures

Adverse Events (AEs)

Number of subjects with adverse events throughout the study.

Concentrations of Cortisol Binding Protein

Cortisol protein binding under physiological conditions and after the administration of dexamethasone and hydrocortisone.

Insulin Sensitivity Under Physiological Conditions and After Administration of Dexamethasone and Infacort®, Hydrocortisone Tablets and i.v Hydrocortisone.

A standardised mixed meal elevates blood glucose and provides a reproducible stimulation of insulin release. Lower levels of insulin secretion, whilst maintaining normoglycaemia would indicate enhanced insulin sensitivity and glucose disposal; higher insulin levels will reflect insulin resistance.

PK and Metabolism of Cortisol

Blood: Serum cortisol under physiological conditions and after administration of dexamethasone and Infacort® Granules, Hydrocortisone Tablets and i.v Hydrocortisone Injection.

Full Information

NCT ID

NCT01960530

First Posted

October 6, 2013

Last Updated

April 5, 2022

Sponsor

Diurnal Limited

Collaborators

Simbec Research

1. Study Identification

Unique Protocol Identification Number

NCT01960530

Brief Title

An Investigational Study of Hydrocortisone

Official Title

An Open Label, Partially Randomised, Single Dose, Crossover Study to Evaluate the PK, Oral Bioavailability and Relationship to Metabolic Parameters of Hydrocortisone and Infacort® in Healthy Adult Male Volunteers.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

October 2013 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Diurnal Limited

Collaborators

Simbec Research

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This study will investigate a new drug called Infacort®; a newly-developed immediate release formulation of a well-established drug called hydrocortisone. Hydrocortisone is used as a replacement treatment for people whose adrenal glands are not producing enough natural cortisol - a condition known as adrenal insufficiency. The study will assess how Infacort® acts once inside the body, by measuring cortisol and other hormone levels in the body, compared to already marketed hydrocortisone tablet and hydrocortisone intravenous (through the vein) injection. The population who are eligible to take part in the study are healthy male volunteers, aged between 18 and 60 years of age.

Detailed Description

The study will evaluate the normal physiology, PK and metabolism of cortisol, investigate the PK and bioavailability of cortisol from the test Infacort® Granules (hydrocortisone) and the reference hydrocortisone tablets and i.v injection in healthy adult male volunteers and explore the role of cortisol in the regulation of metabolic pathways.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Adrenal Insufficiency

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Endogenous Cortisol

Arm Type

No Intervention

Arm Description

Arm Title

Dexamethasone

Arm Type

Other

Arm Description

Arm Title

Infacort®

Arm Type

Experimental

Arm Description

Arm Title

Hydrocortisone Tablet

Arm Type

Active Comparator

Arm Description

Arm Title

i.v Hydrocortisone Injection

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Hydrocortisone granules

Other Intervention Name(s)

Infacort

Intervention Description

Multi-particulate granules

Intervention Type

Drug

Intervention Name(s)

Hydrocortisone Tablet

Other Intervention Name(s)

Commerical supply

Intervention Description

Standard hydrocortisone tablets

Intervention Type

Drug

Intervention Name(s)

i.v. Hydrocortisone Injection

Other Intervention Name(s)

Commerical supply

Intervention Description

Standard hydrocortisone solution for intravenous injection

Intervention Type

Other

Intervention Name(s)

Dexamethasone

Other Intervention Name(s)

Non-IMP

Intervention Description

Challenge agent

Primary Outcome Measure Information:

Title

Maximum Serum Concentration (Cmax)

Description

Derived PK for Serum Cortisol: Maximum serum concentration (Cmax)

Time Frame

Hourly from 0 to 24 hours

Title

AUC0-t

Description

Derived PK for Serum Cortisol: Area under the curve from 0-24 hours

Time Frame

Hourly from 0 to 24 hours

Secondary Outcome Measure Information:

Title

Adverse Events (AEs)

Description

Number of subjects with adverse events throughout the study.

Time Frame

Days 1-2 during each Study Period

Title

Concentrations of Cortisol Binding Protein

Description

Cortisol protein binding under physiological conditions and after the administration of dexamethasone and hydrocortisone.

Time Frame

Blood samples on Day 1 and/or Day 2 of each Study Period

Title

Insulin Sensitivity Under Physiological Conditions and After Administration of Dexamethasone and Infacort®, Hydrocortisone Tablets and i.v Hydrocortisone.

Description

Time Frame

Blood samples on Day 1 and/or Day 2 of each Study Period

Title

PK and Metabolism of Cortisol

Description

Blood: Serum cortisol under physiological conditions and after administration of dexamethasone and Infacort® Granules, Hydrocortisone Tablets and i.v Hydrocortisone Injection.

Time Frame

Blood, urine & saliva samples on Day 1 and/or Day 2 of each Study Period

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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 urinalysis values within 14 days prior to Day 1 of Study Period 1. Subjects with a negative urinary drugs of abuse screen, determined within 14 days prior to Day 1 of Study Period 1. A positive alcohol test may be repeated at the discretion of the Investigator. 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 prior to Day 1 of Study Period 1. Subjects with no clinically-significant deviation outside the normal ranges for blood pressure and pulse measurements. 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 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 spermicide + condom Subjects must be available to complete the study. Subjects must satisfy a medical examiner about their fitness to participate in the study. Subjects must provide 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 prior to Day 1 of Study Period 1 (including high dose vitamins, dietary supplements or herbal remedies). Receipt of any vaccination within 14 days prior to Day 1 of Study Period 1. Evidence of renal, hepatic, central nervous system, respiratory, cardiovascular or metabolic dysfunction. Presence of clinically significant 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. A clinically significant history or family history of psychiatric disorders/illnesses. 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 4 months or a marketed drug clinical study within the previous 3 months. (N.B. The 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 2 units of alcohol per day within seven (7) days prior to Day 1 of Study Period 1or have consumed any alcohol within the 48 hour period prior to Day 1 of Study Period 1. Donation of 450ml or more of blood within the previous 3 months. Subjects who smoke (or ex-smokers who have smoked within 6 months prior to Day 1 of Study Period 1). Subjects who work shifts (i.e. regularly alternate between days, afternoons and nights).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Girish Sharma

Organizational Affiliation

Simbec Research

Official's Role

Principal Investigator

Facility Information:

Facility Name

Simbec Research Limited

City

Merthyr Tydfil

ZIP/Postal Code

CF48 4DR

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

An Investigational Study of Hydrocortisone

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