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

Adrenal Insufficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01735617
• Other study ID #: DIUR-003
• Status: Completed
• Phase: Phase 2
• First received: November 20, 2012
• Last updated: January 6, 2014
• Start date: December 2012
• Est. completion date: December 2013

Study information

• Verified date: January 2014
• Source: Diurnal Limited
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Male or female patients aged 18 and above.

3. Provision of signed written informed consent.

4. Good general health.

5. 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).

6. Plasma renin activity must be within the clinically acceptable range at screening (less than 1.5 times upper normal range).

Exclusion Criteria:

1. Co-morbid condition requiring daily administration of a medication that induces hepatic enzymes or interferes with the metabolism of glucocorticoids.

2. 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.

3. Females who are pregnant or lactating.

4. Women taking an estrogen-containing oral contraceptive pill and who have taken it within 6 weeks of recruitment.

5. Patients taking spironolactone.

6. Patients on inhaled or oral steroids apart from treatment for CAH.

7. Patients with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the trial.

8. Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study.

9. Patients with history of bilateral adrenalectomy.

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adrenal Hyperplasia, Congenital
• Adrenal Insufficiency
• Adrenocortical Hyperfunction
• Adrenogenital Syndrome
• Congenital Adrenal Hyperplasia
• Endocrine Disease
• Endocrine System Diseases
• Hyperplasia

Intervention

Drug:
• Hydrocortisone Modified Release Capsules
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

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Diurnal Limited	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic profile following short-term treatment with Chronocort® in adult patients with congenital adrenal hyperplasia	Area under the plasma concentration versus time curve (AUC) of Chronocort sampled at the following time-points post dosing: 0,2,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,20,24-hours	Single-dose (24-hour)	No
Secondary	Assessment of efficacy profile of Chronocort in relation to 17-hydroxyprogesterone level	Percentage of patients with 17-hydroxyprogesterone (17-OHP) level within proposed optimal range after 2, 4 and 6-months on Chronocort relative to pre-dose baseline	6-months	No
Secondary	Assessment of efficacy profile of Chronocort in relation androstenedione level	Percentage change in androstenedione levels after 2, 4 and 6-months on Chronocort relative to pre-dose baseline	6-months	No
Secondary	Assessment of efficacy profile of Chronocort in relation to adrenocorticotrophic hormone level	Percentage change in adrenocorticotrophic (ACTH) level after 2, 4 and 6-months on Chronocort relative to pre-dose baseline	6-months	No
Secondary	Assessment of efficacy profile of Chronocort in relation to urinary steroidal level	Percentage change in urinary steroidal level after 2, 4 and 6-months on Chronocort relative to pre-dose baseline	6-months	No
Secondary	Assessment of efficacy profile of Chronocort in relation to fasting insulin level	Percentage change in fasting insulin level 2, 4, 6-months on Chronocort relative to pre-dose baseline	6-months	No
Secondary	Assessment of efficacy profile of Chronocort in relation to bone turnover marker serum	Percentage change in bone turnover marker serum, osteocalcin, after 2, 4, 6-months on Chronocort relative to pre-dose baseline	6-months	No
Secondary	Assessment of efficacy profile of Chronocort in relation to blood glucose level	Percentage change in blood glucose level 2, 4, 6-months on Chronocort relative to pre-dose baseline	6-months	No
Secondary	Assessment of efficacy profile of Chronocort in relation to body mass index	Percentage change in body mass index after 2, 4, 6-months on Chronocort relative to pre-dose baseline	6-months	No
Secondary	Assessment of safety profile of Chronocort in relation to reported adverse events	Number of reported adverse events following 6-months treatment with Chronocort	6-months	Yes