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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2 Pilot Study to Characterize and Examine the Pharmacokinetics and Disease Bio-marker Response of Chronocort® in Adults With Congenital Adrenal Hyperplasia

Conditions
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Endocrine Disease, Adrenal Insufficiency, Congenital Adrenal Hyperplasia

Intervention / Treatment
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* Drug: Hydrocortisone Modified Release Capsules


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydrocortisone Modified Release Capsules<br>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 | Drug: Hydrocortisone Modified Release Capsules<br>* Patients with congenital adrenal hyperplasia standardised on conventional therapy is enrolled onto the study and treatment is switched to Chronocort, initially for pharmacokinetic assessment followed by longer-term biochemical and efficacy assessment<br>* Other names: Chronocort;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia | The maximum plasma concentration (Cmax) of chronocort | 24 hours | 
| Pharmacokinetic Profile (AUC0-24) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia | 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) | 24 hours (at 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 | Time to maximum plasma concentration (tmax) | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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 | Specific time point (0700hrs) | 
| 17-OHP Levels at 0700h, 1700h and 2300h | 17-OHP levels at 0700h, 1700h and 2300h | Specified time points (0700h, 1700h and 2300h) | 
| Androstenedione Levels at 0700h, 1700h and 2300h | Androstenedione levels at 0700h, 1700h and 2300h | Specified time points (0700h, 1700h and 2300h) | 
| ACTH Levels at 0700h, 1700h and 2300h | ACTH levels at 0700h, 1700h and 2300h | Specified time points (0700h, 1700h and 2300h) | 
| AUC Values (Nmol*h/L) for Androstenedione | AUC values (nmol*h/L) for Androstenedione for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h | Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h) | 
| AUC Values (Nmol*h/L) for 17-OHP | AUC values (nmol*h/L) for 17-OHP for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h | Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h) | 
| AUC Values (Pmol*h/L) for ACTH | AUC values (pmol*h/L) for ACTH for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h | Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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congenital adrenal hyperplasia, glucocorticoids, cortisol, adrenal