Comparison of Chronocort® With Standard Glucocorticoid Therapy in Patients With Congenital Adrenal Hyperplasia
Condition: Congenital Adrenal Hyperplasia
MeSH terms: Adrenal Hyperplasia, Congenital; Adrenogenital Syndrome; Adrenocortical Hyperfunction; Hyperplasia
Intervention: Chronocort®; standard glucocorticoid therapy
Intervention description: Chronocort® is a patented oral modified release formulation of hydrocortisone which is intended to mimic, or closely match, the serum levels of endogenous cortisol.; Subjects in this arm will continue on their standard hydrocortisone therapy
Intervention MeSH terms: Dexamethasone; Prednisone; Prednisolone; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Glucocorticoids
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 122.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glucocorticoid therapy

Summary:

      This study is a parallel arm, randomised, open-label study, including dose titration and
      admissions for four overnight stays for 24-hour endocrine profiles. It will compare the
      efficacy, safety and tolerability of Chronocort® with standard glucocorticoid replacement
      therapy in the treatment of congenital adrenal hyperplasia (CAH) over a treatment period of 6
      months. Dose titration decisions in both treatment groups will be made by a central
      independent physician, blinded to the treatment arm, using information generated from the
      24-hour endocrine profiles. Each treatment arm will be subject to the same titration rules
      throughout the study, ensuring that opportunities for optimisation and control of androgens
      are the same in both groups.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Known CAH due to 21-hydroxylase deficiency (classic CAH) diagnosed in childhood with
             documented (at any time) elevated 17-OHP and/or 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. Provision of signed written informed consent.

          3. 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.

          4. 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.

          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.

        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 unable to comply with the requirements of the protocol.