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

NCT01735617 | Completed Phase 2 Results

• 1 other identifier: DIUR-003
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Endocrine Disease; Adrenal Insufficiency; Congenital Adrenal Hyperplasia

Keywords

congenital adrenal hyperplasia; glucocorticoids; cortisol; adrenal

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (7)

• 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)

• 17-OHP Levels at 0700h, 1700h and 2300h

  Specified time points (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

  Specified time points (0700h, 1700h and 2300h)

• AUC Values (Nmol*h/L) for Androstenedione

  Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)

Study Arms (1)

Hydrocortisone Modified Release Capsules

EXPERIMENTAL

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

Interventions

Hydrocortisone Modified Release Capsules DRUG

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

Also known as: Chronocort

Hydrocortisone Modified Release Capsules

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• Patients with history of bilateral adrenalectomy.

Sponsors & Collaborators

• Neurocrine UK Limited: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892-1932, United States

Location

Related Publications (1)

• Mallappa A, Sinaii N, Kumar P, Whitaker MJ, Daley LA, Digweed D, Eckland DJ, Van Ryzin C, Nieman LK, Arlt W, Ross RJ, Merke DP. A phase 2 study of Chronocort, a modified-release formulation of hydrocortisone, in the treatment of adults with classic congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2015 Mar;100(3):1137-45. doi: 10.1210/jc.2014-3809. Epub 2014 Dec 11.

  PMID: 25494662 DERIVED

MeSH Terms

Conditions

Endocrine System Diseases; Adrenal Insufficiency; Adrenal Hyperplasia, Congenital

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Adrenogenital Syndrome; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Steroid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Gonadal Disorders

Results Point of Contact

• Title: CEO
• Organization: Diurnal Ltd.

info@diurnal.co.uk

+44 (0) 871 716 8848

Study Officials

• Deborah P Merke, BS, MS, MD

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2012
• First Posted: November 28, 2012
• Study Start: December 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: May 17, 2017
• Results First Posted: May 17, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)