Clinical trial NCT01735617: Pilot Study to Characterize and Examine the Pharmacokinetics and Efficacy of Chronocort® in Adults With CAH
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endocrine Disease
Adrenal Insufficiency
Congenital Adrenal Hyperplasia
Keywords: congenital adrenal hyperplasia
glucocorticoids
cortisol
adrenal
Lead sponsor: Neurocrine UK Limited
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
First posted: 2012-11-28
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia
timeFrame: 24 hours
measure: Pharmacokinetic Profile (AUC0-24) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia
timeFrame: 24 hours (at 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs)
measure: Pharmacokinetic Profile (Tmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia
timeFrame: 24 hours
Secondary outcomes:
measure: 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)
timeFrame: Specific time point (0700hrs)
measure: 17-OHP Levels at 0700h, 1700h and 2300h
timeFrame: Specified time points (0700h, 1700h and 2300h)
measure: Androstenedione Levels at 0700h, 1700h and 2300h
timeFrame: Specified time points (0700h, 1700h and 2300h)
measure: ACTH Levels at 0700h, 1700h and 2300h
timeFrame: Specified time points (0700h, 1700h and 2300h)
measure: AUC Values (Nmol*h/L) for Androstenedione
timeFrame: Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)
measure: AUC Values (Nmol*h/L) for 17-OHP
timeFrame: Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)
measure: AUC Values (Pmol*h/L) for ACTH
timeFrame: Specific time points (2300-2300h, 2300-0700h, 0700-1500h and 1500-2300h)
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
Study officials:
affiliation: National Institutes of Health Clinical Center (CC)
name: Deborah P Merke, BS, MS, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.