Clinical Trials

Inclusion Criteria:

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

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

- Participants with known classic CAH due to 21 hydroxylase deficiency diagnosed in
childhood with documented (at any time) elevated 17-OHP and with or without elevated
A4 and currently treated with hydrocortisone, prednisone, prednisolone or
dexamethasone (or a combination of the aforementioned glucocorticoids) and on stable
glucocorticoid therapy for a minimum of 3 months.

- Participants who are receiving fludrocortisone must be on a documented stable dose for
a minimum of 3 months prior to enrollment and must have stable renin levels at
screening.

- Female participants of childbearing potential and all male participants must agree to
the use of an accepted method of contraception during the study.

- A female participant is eligible to participate if she is not pregnant, not
breastfeeding, and she is either not a woman of childbearing potential (WOCBP) or has
a negative pregnancy test at entry into the study. Note: females presenting with
oligomenorrhea or amenorrhea who are aged ≤55 years should be considered potentially
fertile and therefore should undergo pregnancy testing like all other female
participants.

- Capable of giving signed informed consent/assent which includes compliance with
requirements and restrictions listed in the informed consent form (ICF) and in this
protocol.

Exclusion Criteria:

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

- History of bilateral adrenalectomy.

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

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

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

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

- Participants on regular daily inhaled, topical, nasal or oral steroids for any
indication other than CAH.

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

- Participants who are receiving <10 mg hydrocortisone dose at screening or the
hydrocortisone dose equivalent.

- Participants anticipating regular prophylactic use of additional steroids e.g. for
strenuous exercise.

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

- Inclusion in any natural history or translational research study that would require
evaluation of androgen levels during the study period outside of this protocol's
assessments.

- 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 usual
night-time hours.

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

- Participants with a known hypersensitivity to any of the components of the Chronocort
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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 1/18/23. Questions regarding updates should be directed to the study team contact.