Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH

Phase 2

Completed

Conditions: Endocrine Disease
Adrenal Insufficiency
Congenital Adrenal Hyperplasia

Brief Summary: The purpose of this study is to gather safety and effectiveness information about a new formulation of Hydrocortisone (Chronocort®) used to treat patients with a disease called congenital adrenal hyperplasia (CAH). Hydrocortisone is the man-made version of the hormone cortisol, which is released in the body following a regular daily pattern. The objective of the study is to measure the levels of hydrocortisone that are absorbed into the bloodstream once Chronocort® is taken and what affects it has on other hormones in the body. Since Chronocort® is anticipated to mimic the same release pattern of cortisol in the body, it is hoped that patients with CAH will be treated more effectively to manage their disease.

Detailed Description: This study is a Phase 2 pilot study to characterize and examine the pharmacokinetics and efficacy profile of Chronocort® in adults with congenital adrenal hyperplasia (CAH). It is designed as a two-part, single cohort, open label, multiple dose Phase 2 pilot study to: (Part A) characterize and examine the pharmacokinetics (PK) and disease bio-marker behavior following short-term dosing with Chronocort®; and to (Part B) examine the disease control after six months dose titration with Chronocort® in adults with CAH.

Recruitment & Eligibility

Inclusion Criteria

Known CAH due to 21-hydroxylase deficiency (classic CAH) based on hormonal and genetic testing currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone on a stable dosage for a minimum of 3 months.
Male or female patients aged 18 and above.
Provision of signed written informed consent.
Good general health.
Females of childbearing potential must have a negative pregnancy test initially and at all visits. Females who are engaging in sexual intercourse must be using a medically acceptable method of contraception (as defined in the protocol, section 10.5).
Plasma renin activity must be within the clinically acceptable range at screening (less than 1.5 times upper normal range).

Exclusion Criteria

Co-morbid condition requiring daily administration of a medication that induces hepatic enzymes or interferes with the metabolism of glucocorticoids.
Clinical or biochemical evidence of hepatic or renal disease. Creatinine above the normal range or elevated liver function tests (ALT or AST) > 2 times the upper limits of normal.
Females who are pregnant or lactating.
Women taking an estrogen-containing oral contraceptive pill and who have taken it within 6 weeks of recruitment.
Patients taking spironolactone.
Patients on inhaled or oral steroids apart from treatment for CAH.
Patients with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the trial.
Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study.
Patients with history of bilateral adrenalectomy.

Arm && Interventions

Group	Intervention	Description
Hydrocortisone Modified Release Capsules	Hydrocortisone Modified Release Capsules	Chronocort Modified Release Capsules, 5mg, 10mg and 20mg Dosing frequency twice-daily (mane and nocte) Dose setting by titration to achieve optimal biochemical and therapeutic response

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia	24 hours	The maximum plasma concentration (Cmax) of chronocort
Pharmacokinetic Profile (AUC0-24) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia	24 hours (at 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs)	Area under the curve (AUC) from 0 to 24 hours (sampling occurs at the following timepoints: 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs)
Pharmacokinetic Profile (Tmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia	24 hours	Time to maximum plasma concentration (tmax)

Secondary Outcome Measures

Name	Time	Method
ACTH Levels at 0700h, 1700h and 2300h	Specified time points (0700h, 1700h and 2300h)	ACTH levels at 0700h, 1700h and 2300h
Androstenedione Levels at 0700h, 1700h and 2300h	Specified time points (0700h, 1700h and 2300h)	Androstenedione levels at 0700h, 1700h and 2300h
17-OHP Levels at 0700h, 1700h and 2300h	Specified time points (0700h, 1700h and 2300h)	17-OHP levels at 0700h, 1700h and 2300h
AUC Values (Nmol*h/L) for 17-OHP	Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)	AUC values (nmol\*h/L) for 17-OHP for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h
The Percentage of Patients With 17-OHP and Androstenedione Levels at 0700h Within Proposed Optimal Ranges Whilst on Chronocort and Whilst on Standard Therapy (at Baseline)	Specific time point (0700hrs)	Proposed optimal ranges of 17-OHP: 300-1200ng/dl Proposed optimal ranges of androstenedione: 40-150ng.dl for males and 30-200ng/dl for females
AUC Values (Nmol*h/L) for Androstenedione	Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)	AUC values (nmol\*h/L) for Androstenedione for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h
AUC Values (Pmol*h/L) for ACTH	Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)	AUC values (pmol\*h/L) for ACTH for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h