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

Primary Purpose

Endocrine Disease, Adrenal Insufficiency, Congenital Adrenal Hyperplasia

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Hydrocortisone Modified Release Capsules

About this trial

This is an interventional treatment trial for Endocrine Disease focused on measuring congenital adrenal hyperplasia, glucocorticoids, cortisol, adrenal

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

National Institutes of Health Clinical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hydrocortisone Modified Release Capsules

Arm Description

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

Outcomes

Primary Outcome Measures

Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia

The maximum plasma concentration (Cmax) of chronocort

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)

Pharmacokinetic Profile (Tmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia

Time to maximum plasma concentration (tmax)

Secondary Outcome Measures

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

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

17-OHP levels at 0700h, 1700h and 2300h

Androstenedione Levels at 0700h, 1700h and 2300h

Androstenedione levels at 0700h, 1700h and 2300h

ACTH Levels at 0700h, 1700h and 2300h

ACTH levels at 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

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

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

Full Information

NCT ID

NCT01735617

First Posted

November 20, 2012

Last Updated

April 11, 2017

Sponsor

Diurnal Limited

Collaborators

National Institutes of Health (NIH)

1. Study Identification

Unique Protocol Identification Number

NCT01735617

Brief Title

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

2. Study Status

Record Verification Date

April 2017

Overall Recruitment Status

Completed

Study Start Date

December 2012 (undefined)

Primary Completion Date

December 2013 (Actual)

Study Completion Date

December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Diurnal Limited

Collaborators

National Institutes of Health (NIH)

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Endocrine Disease, Adrenal Insufficiency, Congenital Adrenal Hyperplasia

Keywords

congenital adrenal hyperplasia, glucocorticoids, cortisol, adrenal

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hydrocortisone Modified Release Capsules

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Hydrocortisone Modified Release Capsules

Other Intervention Name(s)

Chronocort

Intervention Description

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

Primary Outcome Measure Information:

Title

Pharmacokinetic Profile (Cmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia

Description

The maximum plasma concentration (Cmax) of chronocort

Time Frame

24 hours

Title

Pharmacokinetic Profile (AUC0-24) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia

Description

Time Frame

24 hours (at 2300, 0100, 0300, 0500, 0600, 0700, 0800, 0900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1900, 2100, 2300hrs)

Title

Pharmacokinetic Profile (Tmax) Following Short-term Treatment With Chronocort® in Adult Patients With Congenital Adrenal Hyperplasia

Description

Time to maximum plasma concentration (tmax)

Time Frame

24 hours

Secondary Outcome Measure Information:

Title

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)

Description

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

Time Frame

Specific time point (0700hrs)

Title

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

Description

17-OHP levels at 0700h, 1700h and 2300h

Time Frame

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

Title

Androstenedione Levels at 0700h, 1700h and 2300h

Description

Androstenedione levels at 0700h, 1700h and 2300h

Time Frame

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

Title

ACTH Levels at 0700h, 1700h and 2300h

Description

ACTH levels at 0700h, 1700h and 2300h

Time Frame

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

Title

AUC Values (Nmol*h/L) for Androstenedione

Description

AUC values (nmol*h/L) for Androstenedione for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h

Time Frame

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

Title

AUC Values (Nmol*h/L) for 17-OHP

Description

AUC values (nmol*h/L) for 17-OHP for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h

Time Frame

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

Title

AUC Values (Pmol*h/L) for ACTH

Description

AUC values (pmol*h/L) for ACTH for the following reporting periods: 24 hours (2300-2300h), 2300-0700h, 0700-1500h and 1500-2300h

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Deborah P Merke, BS, MS, MD

Organizational Affiliation

National Institutes of Health Clinical Center (CC)

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Institutes of Health Clinical Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892-1932

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

25494662

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.

Results Reference

derived

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

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