Chronocort®, a slow release medicinal preparation of hydrocortisone, will be compared with currently used glucocorticoid replacement therapy in the treatment of congenital adrenal hyperplasia seeking to assess its safety, tolerability and effectiveness.

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2015-000711-40-GB
• Date of registration: 28/07/2015
• Prospective Registration: Yes
• Primary sponsor: Diurnal Ltd
• Public title: Chronocort®, a slow release medicinal preparation of hydrocortisone, will be compared with currently used glucocorticoid replacement therapy in the treatment of congenital adrenal hyperplasia seeking to assess its safety, tolerability and effectiveness.
• Scientific title: A Phase III study of efficacy, safety and tolerability of Chronocort® compared with standard glucocorticoid replacement therapy in the treatment of congenital adrenal hyperplasia.
• Date of first enrolment: 19/11/2015
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-000711-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Denmark, France, Germany, Netherlands, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Trials Information
• Affiliation: Diurnal Ltd

• Name: Clinical Trials Information
• Affiliation: Diurnal Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1. Known CAH due to 21-hydroxylase deficiency (classic CAH) diagnosed in childhood with documented (at any time) elevated 17-hydroxyprogesterone (17-OHP) and/or androstenedione (A4) and currently treated with hydrocortisone, prednisone, prednisolone or dexamethasone (or a combination of the aforementioned glucocorticoids) on a stable glucocorticoid therapy for a minimum of 6 months.
2. Male or female subjects aged 18 and above.
3. Provision of signed written informed consent.
4. Non-pregnant, non-lactating females who are post menopausal, naturally or surgically sterile, or of childbearing potential with a negative urinary pregnancy test and using a medically acceptable method of contraception. (Note: females presenting with oligomenorrhoea or amenorrhoea who are aged =55 years of age should be considered potentially fertile and therefore, as well as undergoing pregnancy testing like all other female subjects, will be expected to be using an acceptable method of contraception).
5. Plasma renin activity (PRA) less than 1.5 times the upper limit of normal (ULN) at screening or within 3 months prior to screening, except in subjects who have been diagnosed with hypertension where the renin is not being used to monitor fludrocortisone replacement.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 120
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Co-morbid condition requiring daily administration of a medication (or consumption of any material) that interferes with the metabolism of glucocorticoids.
2. Clinical or biochemical evidence of hepatic or renal disease. Creatinine over twice the ULN or elevated liver function tests (ALT or AST >2 times the ULN).
3. Subjects on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH.
4. Subjects with any other significant medical or psychiatric conditions that in the opinion of the investigator would preclude participation in the trial.
5. History of malignancy (other than basal cell carcinoma successfully treated >6 months prior to entry into the study).
6. Participation in another clinical trial of an investigational or licensed drug or device within the 3 months prior to inclusion in this study.
7. Subjects with a history of bilateral adrenalectomy.
8. Subjects having previously been exposed to Chronocort®.
9. Subjects who routinely work night shifts and so do not sleep during the usual nighttime hours.
10. Subjects unable to comply with the requirements of the protocol.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Congenital adrenal hyperplasia (CAH); is generally due to 21-hydroxylase deficiency, is a disease of the adrenal cortex characterised by cortisol deficiency with or without aldosterone deficiency, and androgen excess. Subjects with CAH are at risk of developing a number of clinical manifestations, such as obesity in children, insulin resistance, and polycystic ovaries, which may contribute to infertility in women with CAH. Oligomenorrhoea or amenorrhoea may be present in adolescence.
MedDRA version: 20.0 Level: LLT Classification code 10010323 Term: Congenital adrenal hyperplasia System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Intervention(s)

Product Name: Chronocort®
Product Code: DIURF-006
Pharmaceutical Form: Capsule
INN or Proposed INN: HYDROCORTISONE
CAS Number: 50-23-7
Other descriptive name: Cortisol
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 5-20

Trade Name: Hydrocortisone 20mg Tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Hydrocortisone
CAS Number: 50-23-7
Other descriptive name: HYDROCORTISONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: Dexamethasone 2mg Tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: DEXAMETHASONE
CAS Number: 50-02-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: Prednisolone 1mg Tablets
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisolone
CAS Number: 50-24-8
Other descriptive name: PREDNISOLONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Primary end point(s): The primary efficacy endpoint is the change from baseline to 24 weeks of the mean of the 24-hour standard deviation score (SDS) profile for 17-OHP. The SDS profile is calculated as the SDS of log transformed 17 OHP concentration unsigned.

Secondary Objective: In adult subjects with CAH:
• To assess the safety and tolerability of Chronocort® treatment in adult subjects with CAH over a 6-month period.
• To assess the efficacy of Chronocort® with regard to the effect on androstenedione [A4] levels over the 6 month treatment period.
• To assess the impact of Chronocort® on body composition (using dual energy X-ray absorbtimetry [DEXA]) – fat mass, lean mass and total bone density – at selected sites.

Timepoint(s) of evaluation of this end point: Baseline and 24 weeks

Main Objective: To demonstrate the superior efficacy of Chronocort® compared with standard glucocorticoid replacement therapy in the treatment of congenital adrenal hyperplasia (CAH). This will be assessed by establishing whether Chronocort® can provide improved control of serum androgen levels compared to current glucocorticoid treatment regimens.

Secondary Outcome(s)

Secondary end point(s): 1. The change from baseline to 24 weeks of the mean of the 24-hour SDS profile for A4 (calculated in the same way as the primary endpoint).
2. The presentation of 17-OHP and A4 by individual baseline treatment strata in the study will be presented in the same manner as the primary endpoint (using 24-hour SDS profile at 24 weeks).
3. 17-OHP and A4 levels at 09:00 as a responder analysis (i.e. the number of subjects achieving results in the optimal range).
4. Changes relative to standard glucocorticoid replacement therapy in body composition (DEXA) (fat mass, lean mass and total bone density) to be measured at all sites except Germany.

Timepoint(s) of evaluation of this end point: Baseline and 24 weeks

Secondary ID(s)

DIUR-005

Source(s) of Monetary Support

Diurnal Ltd

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 26/07/2019
• Date Completed: 28/07/2018
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000711-40/results