Comparison of Chronocort Versus Standard Hydrocortisone Replacement Therapy in Participants Aged 16 Years and Over With Congenital Adrenal Hyperplasia

Inclusion Criteria:

• Male or female participants must be aged 16 years or older at the time of signingthe informed consent/assent.

• In participants aged <18 years, height velocity must be less than 2 cm/year in thelast year and puberty must be completed (Tanner stage V).

• Participants with known classic CAH due to 21 hydroxylase deficiency diagnosed inchildhood with documented (at any time) elevated 17-OHP and with or without elevatedA4 and currently treated with hydrocortisone, prednisone, prednisolone ordexamethasone (or a combination of the aforementioned glucocorticoids) and on stableglucocorticoid therapy for a minimum of 3 months.

• Participants who are receiving fludrocortisone must be on a documented stable dosefor a minimum of 3 months prior to enrollment and must have stable renin levels atscreening.

• Female participants of childbearing potential and all male participants must agreeto the use of an accepted method of contraception during the study.

• A female participant is eligible to participate if she is not pregnant, notbreastfeeding, and she is either not a woman of childbearing potential (WOCBP) orhas a negative pregnancy test at entry into the study. Note: females presenting witholigomenorrhea or amenorrhea who are aged ≤55 years should be considered potentiallyfertile and therefore should undergo pregnancy testing like all other femaleparticipants.

• Capable of giving signed informed consent/assent which includes compliance withrequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol.

Exclusion Criteria:

• Clinical or biochemical evidence of hepatic or renal disease e.g. creatinine >2times the upper limit of normal (ULN) or elevated liver function tests (alanineaminotransferase [ALT] or aspartate aminotransferase [AST] >2 times the ULN).

• History of bilateral adrenalectomy.

• History of malignancy (other than basal cell carcinoma successfully treated >26weeks prior to entry into the study).

• Participants who have type 1 diabetes or receive regular insulin, have uncontrolleddiabetes, or have a screening HbA1c greater than 8%.

• Persistent signs of adrenal insufficiency or the participant does not toleratetreatment at the end of the 4-week run-in period.

• Participants with any other significant medical or psychiatric conditions that inthe opinion of the Investigator would preclude participation in the study.

• Participants on regular daily inhaled, topical, nasal or oral steroids for anyindication other than CAH.

• Co-morbid condition requiring daily administration of a medication or consumption ofany material that interferes with the metabolism of glucocorticoids.

• Participants who are receiving <10 mg hydrocortisone dose at screening or thehydrocortisone dose equivalent.

• Participants anticipating regular prophylactic use of additional steroids e.g. forstrenuous exercise.

• Participation in another clinical study of an investigational or licensed drug ordevice within the 12 weeks prior to screening.

• Inclusion in any natural history or translational research study that would requireevaluation of androgen levels during the study period outside of this protocol'sassessments.

• Participants who have previously been exposed to Chronocort in any Diurnal study.

• Participants who routinely work night shifts and so do not sleep during the usualnight-time hours.

• Participants, who in the opinion of the Investigator, will be unable to comply withthe requirements of the protocol.

• Participants with a known hypersensitivity to any of the components of theChronocort capsules, the Cortef tablets, or the placebo capsules.

• Participants with congenital galactosemia, malabsorption of glucose and galactose,or who are lactase deficient.

• Participants with a body weight of 45 kg or less.