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

Purpose

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.

Condition	Intervention	Phase
Endocrine Disease Adrenal Insufficiency Congenital Adrenal Hyperplasia	Drug: Hydrocortisone Modified Release Capsules	Phase 2

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

Resource links provided by NLM:

Genetics Home Reference related topics: 21-hydroxylase deficiency 3-beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency Cushing disease persistent Müllerian duct syndrome

MedlinePlus related topics: Endocrine Diseases

Drug Information available for: Hydrocortisone acetate Hydrocortisone Epinephrine bitartrate Epinephrine Epinephrine hydrochloride Hydrocortisone sodium succinate Racepinephrine hydrochloride Racepinephrine Hydrocortisone cypionate Hydrocortisone butyrate Hydrocortisone valerate Hydrocortisone probutate

U.S. FDA Resources

Further study details as provided by Diurnal Limited:

Primary Outcome Measures:

Pharmacokinetic profile following short-term treatment with Chronocort® in adult patients with congenital adrenal hyperplasia [ Time Frame: Single-dose (24-hour) ] [ Designated as safety issue: No ]
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

Secondary Outcome Measures:

Assessment of efficacy profile of Chronocort in relation to 17-hydroxyprogesterone level [ Time Frame: 6-months ] [ Designated as safety issue: No ]
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
Assessment of efficacy profile of Chronocort in relation androstenedione level [ Time Frame: 6-months ] [ Designated as safety issue: No ]
Percentage change in androstenedione levels after 2, 4 and 6-months on Chronocort relative to pre-dose baseline
Assessment of efficacy profile of Chronocort in relation to adrenocorticotrophic hormone level [ Time Frame: 6-months ] [ Designated as safety issue: No ]
Percentage change in adrenocorticotrophic (ACTH) level after 2, 4 and 6-months on Chronocort relative to pre-dose baseline
Assessment of efficacy profile of Chronocort in relation to urinary steroidal level [ Time Frame: 6-months ] [ Designated as safety issue: No ]
Percentage change in urinary steroidal level after 2, 4 and 6-months on Chronocort relative to pre-dose baseline
Assessment of efficacy profile of Chronocort in relation to fasting insulin level [ Time Frame: 6-months ] [ Designated as safety issue: No ]
Percentage change in fasting insulin level 2, 4, 6-months on Chronocort relative to pre-dose baseline
Assessment of efficacy profile of Chronocort in relation to bone turnover marker serum [ Time Frame: 6-months ] [ Designated as safety issue: No ]
Percentage change in bone turnover marker serum, osteocalcin, after 2, 4, 6-months on Chronocort relative to pre-dose baseline
Assessment of efficacy profile of Chronocort in relation to blood glucose level [ Time Frame: 6-months ] [ Designated as safety issue: No ]
Percentage change in blood glucose level 2, 4, 6-months on Chronocort relative to pre-dose baseline
Assessment of efficacy profile of Chronocort in relation to body mass index [ Time Frame: 6-months ] [ Designated as safety issue: No ]
Percentage change in body mass index after 2, 4, 6-months on Chronocort relative to pre-dose baseline
Assessment of safety profile of Chronocort in relation to reported adverse events [ Time Frame: 6-months ] [ Designated as safety issue: Yes ]
Number of reported adverse events following 6-months treatment with Chronocort

Estimated Enrollment:	16
Study Start Date:	December 2012
Estimated Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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	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 Other Name: Chronocort

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735617

Contacts

Contact: Ashwini Mallappa, MD		Ashwini.mallappa@nih.gov
Contact: Carol Van Ryzin, RN CPNP		CVanRyzin@cc.nih.gov

Locations

United States, Maryland
National Institutes of Health Clinical Center	Recruiting
Bethesda, Maryland, United States, 20892-1932
Contact: Ashwini Mallappa, MD Ashwini.mallappa@nih.gov
Contact: Carol Van Ryzen, RN CPNP mailto:CVanRyzin@cc.nih.gov
Principal Investigator: Deborah P Merke, BS MS MD

Sponsors and Collaborators

Diurnal Limited

National Institutes of Health (NIH)

Investigators

Principal Investigator:

Deborah P Merke, BS, MS, MD

National Institutes of Health Clinical Center (CC)

More Information

No publications provided

Responsible Party:	Diurnal Limited
ClinicalTrials.gov Identifier:	NCT01735617 History of Changes
Other Study ID Numbers:	DIUR-003
Study First Received:	November 20, 2012
Last Updated:	December 5, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Diurnal Limited:

congenital adrenal hyperplasia
glucocorticoids
cortisol
adrenal

Additional relevant MeSH terms:

Adrenal Hyperplasia, Congenital
Adrenogenital Syndrome
Adrenal Insufficiency
Addison Disease
Adrenocortical Hyperfunction
Endocrine System Diseases
Hyperplasia
Adrenal Gland Diseases
Autoimmune Diseases
Immune System Diseases
Disorders of Sex Development
Urogenital Abnormalities
Congenital Abnormalities
Genetic Diseases, Inborn

Steroid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases
Gonadal Disorders
Pathologic Processes
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents

ClinicalTrials.gov processed this record on May 21, 2013