An Investigational Study of Hydrocortisone

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.

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.

Study Overview

• Status: Completed
• Conditions: Adrenal Insufficiency
• Intervention / Treatment: Other: Dexamethasone; Drug: Hydrocortisone granules; Drug: Hydrocortisone Tablet; Drug: i.v. Hydrocortisone Injection

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Merthyr Tydfil, United Kingdom, CF48 4DR
    • Simbec Research Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Endogenous Cortisol; 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.
OTHER: Dexamethasone; 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	Other: Dexamethasone; Challenge agent; Other Names: Non-IMP
EXPERIMENTAL: Infacort®; 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.	Drug: Hydrocortisone granules; Multi-particulate granules; Other Names: Infacort
ACTIVE_COMPARATOR: Hydrocortisone Tablet; 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.	Drug: Hydrocortisone Tablet; Standard hydrocortisone tablets; Other Names: Commerical supply
ACTIVE_COMPARATOR: i.v Hydrocortisone Injection; 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.	Drug: i.v. Hydrocortisone Injection; Standard hydrocortisone solution for intravenous injection; Other Names: Commerical supply

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Serum Concentration (Cmax)	Derived PK for Serum Cortisol: Maximum serum concentration (Cmax)	Hourly from 0 to 24 hours
AUC0-t	Derived PK for Serum Cortisol: Area under the curve from 0-24 hours	Hourly from 0 to 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Number of subjects with adverse events throughout the study.	Days 1-2 during each Study Period
Concentrations of Cortisol Binding Protein	Cortisol protein binding under physiological conditions and after the administration of dexamethasone and hydrocortisone.	Blood samples on Day 1 and/or Day 2 of each Study Period
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.	Blood samples on Day 1 and/or Day 2 of each Study Period
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.	Blood, urine & saliva samples on Day 1 and/or Day 2 of each Study Period

Collaborators and Investigators

• Sponsor: Diurnal Limited
• Collaborators: Simbec Research

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: October 6, 2013
• First Submitted That Met QC Criteria: October 9, 2013
• First Posted (ESTIMATE): October 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): April 26, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Adrenal Gland Diseases; Adrenal Insufficiency; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate
• Other Study ID Numbers: Infacort 002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO