Trial Outcomes & Findings for An Investigational Study of Hydrocortisone (NCT NCT01960530)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

Hourly from 0 to 24 hours

Results posted on

2022-04-26

Participant Flow

Participant milestones

Participant milestones
Measure	5-period Crossover Study Period 1 (Endogenous Cortisol): No IMP was administered. Subjects were observed over a 24 hour period, during which sleep disruption was minimised, to record their endogenous cortisol production as a baseline figure and to confirm eligibility for the subsequent study periods. Study Period 2 (Dexamethasone): Subjects were admitted to the unit following a final confirmation of eligibility, prior to administration with Dexamethasone. Study Periods 3 and 4 (Infacort Granules or Hydrocortisone Tablets): Subjects were admitted to the unit and ongoing eligibility was confirmed. Subjects received both treatments (1 in Period 3, and 1 in Period 4), and were randomised using the PROC PLAN procedure of SAS. Subjects received Dexamethasone 1 hour prior to IMP administration. Study Period 5 (I.V. Hydrocortisone Injection): Subjects were admitted to the unit and ongoing eligibility was confirmed. Subjects received Dexamethasone 1 hour prior to IMP administration.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

An Investigational Study of Hydrocortisone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=14 Participants All participants received no IMP, dexamethasone (non-IMP), oral infacort, oral hydrocortisone, i.v. hydrocortisone
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=99 Participants
Age, Categorical >=65 years	0 Participants n=99 Participants
Age, Continuous	32.9 years STANDARD_DEVIATION 11.66 • n=99 Participants
Sex: Female, Male Female	0 Participants n=99 Participants
Sex: Female, Male Male	14 Participants n=99 Participants
Region of Enrollment United Kingdom	14 participants n=99 Participants

PRIMARY outcome

Timeframe: Hourly from 0 to 24 hours

Population: All randomised subjects who received no IMP (no treatment), dexamethasone, oral Infacort®, hydrocortisone tablet and i.v. hydrocortisone, had sufficient serum cortisol concentration by time profiles and who did not violate the protocol

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

Outcome measures

Outcome measures
Measure	Infacort® n=14 Participants 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. Infacort	Hydrocortisone Tablet n=14 Participants 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. Hydrocortisone Tablet	i.v Hydrocortisone Injection n=14 Participants 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. i.v. Hydrocortisone Injection	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. Hydrocortisone Tablet	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. i.v. Hydrocortisone Injection
Maximum Serum Concentration (Cmax)	940.012 nmol/L Standard Deviation 283.773	896.489 nmol/L Standard Deviation 258.083	1563.479 nmol/L Standard Deviation 491.267	—	—

PRIMARY outcome

Timeframe: Hourly from 0 to 24 hours

Population: All randomised subjects who received no IMP (no treatment), dexamethasone, oral Infacort®, hydrocortisone tablet and i.v. hydrocortisone, had sufficient serum cortisol concentration by time profiles and who did not violate the protocol

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

Outcome measures

Outcome measures
Measure	Infacort® n=14 Participants 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. Infacort	Hydrocortisone Tablet n=13 Participants 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. Hydrocortisone Tablet	i.v Hydrocortisone Injection n=14 Participants 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. i.v. Hydrocortisone Injection	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. Hydrocortisone Tablet	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. i.v. Hydrocortisone Injection
AUC0-t	2543.24 nmol*h/L Standard Deviation 713.76	2896.73 nmol*h/L Standard Deviation 850.31	2923.46 nmol*h/L Standard Deviation 971.41	—	—

SECONDARY outcome

Timeframe: Days 1-2 during each Study Period

Number of subjects with adverse events throughout the study.

Outcome measures

Outcome measures
Measure	Infacort® n=14 Participants 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. Infacort	Hydrocortisone Tablet n=14 Participants 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. Hydrocortisone Tablet	i.v Hydrocortisone Injection n=14 Participants 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. i.v. Hydrocortisone Injection	Hydrocortisone Tablet n=14 Participants 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. Hydrocortisone Tablet	i.v Hydrocortisone Injection n=14 Participants 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. i.v. Hydrocortisone Injection
Adverse Events (AEs)	3 participants	3 participants	0 participants	1 participants	2 participants

SECONDARY outcome

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

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

Outcome measures

Outcome measures
Measure	Infacort® n=14 Participants 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. Infacort	Hydrocortisone Tablet n=14 Participants 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. Hydrocortisone Tablet	i.v Hydrocortisone Injection n=14 Participants 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. i.v. Hydrocortisone Injection	Hydrocortisone Tablet n=14 Participants 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. Hydrocortisone Tablet	i.v Hydrocortisone Injection n=14 Participants 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. i.v. Hydrocortisone Injection
Concentrations of Cortisol Binding Protein	22.950 ug/mL Standard Deviation 2.7355	23.441 ug/mL Standard Deviation 3.0381	22.386 ug/mL Standard Deviation 2.8753	21.757 ug/mL Standard Deviation 3.6545	21.482 ug/mL Standard Deviation 3.2047

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Infacort® n=14 Participants 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. Infacort	Hydrocortisone Tablet n=14 Participants 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. Hydrocortisone Tablet	i.v Hydrocortisone Injection n=14 Participants 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. i.v. Hydrocortisone Injection	Hydrocortisone Tablet n=14 Participants 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. Hydrocortisone Tablet	i.v Hydrocortisone Injection n=14 Participants 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. i.v. Hydrocortisone Injection
Insulin Sensitivity Under Physiological Conditions and After Administration of Dexamethasone and Infacort®, Hydrocortisone Tablets and i.v Hydrocortisone.	70.529 uIU/mL Standard Deviation 17.975	80.668 uIU/mL Standard Deviation 40.801	77.575 uIU/mL Standard Deviation 32.195	70.650 uIU/mL Standard Deviation 34.983	70.121 uIU/mL Standard Deviation 27.140

SECONDARY outcome

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

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