Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency
Conditions
Sponsors
Diurnal Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be aged 16 years or older at the time of signing the informed consent/assent. 2. In participants aged =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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). 2. History of bilateral adrenalectomy. 3. History of malignancy (other than basal cell carcinoma successfully treated >26 weeks prior to entry into the study). 4. Participants who have type 1 diabetes or receive regular insulin. 5. Persistent signs of adrenal insufficiency or the participant does not tolerate treatment at the end of the 4-week run-in period. 6. Participants with any other significant medical or psychiatric conditions that in the opinion of the Investigator would preclude participation in the study. 7. Participants on regular daily inhaled, topical, nasal or oral steroids for any indication other than CAH. 8. Co-morbid condition requiring daily administration of a medication or consumption of any material that interferes with the metabolism of glucocorticoids (examples provided at http://medicine.iupui.edu/clinpharm/ddis/clinical-table/). 9. Participants who are receiving <10 mg hydrocortisone dose at baseline or the hydrocortisone dose equivalent. 10. Participants anticipating regular prophylactic use of additional steroids e.g. for strenuous exercise. 11. Participation in another clinical study of an investigational or licensed drug or device within the 12 weeks prior to screening. 12. 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. 13. Participants who have previously been exposed to Chronocort in any Diurnal study. 14. Participants who routinely work night shifts and so do not sleep during the usual night-time hours. 15. Participants, who in the opinion of the Investigator, will be unable to comply with the requirements of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare Chronocort to immediate-release hydrocortisone replacement therapy (IRHC) in terms of biochemical responder rate after 52 weeks of randomized treatment.;Secondary Objective: 1. To compare Chronocort to IRHC in terms of dose responder rate after 52 weeks of randomized treatment. 2. To compare Chronocort to IRHC in terms of total daily dose after 52 weeks of randomized treatment.;Primary end point(s): The primary efficacy outcome variable is whether or not the participant is a biochemical responder after 52 weeks of randomized treatment. A biochemical responder is a participant who: i) is in biochemical control at the 08:00 hours assessment after 52 weeks of randomized treatment (where in biochemical control is defined as both a 17-OHP concentration equal to or below the upper limit for optimal control and an A4 concentration equal to or below the upper limit of the reference range), and ii) is receiving after 52 weeks of randomized treatment a total daily dose of hydrocortisone of not more than 25 mg (if the participant was in biochemical control at baseline) or not more than 30 mg (if the participant was not in biochemical control at baseline). The primary null hypothesis is that the response rate in the Chronocort arm is worse than or equal to the response rate in the IRHC arm minus 10 percentage points. The primary alternate hypothesis is that the response rate in the Chronocort arm is better than the response rate in the IRHC arm minus 10 percentage points. Biochemical non-inferiority of Chronocort to IRHC will be declared if the 95% CI for the difference in response rates between the 2 treatment arms (Chronocort minus IRHC) is wholly above minus 10 percentage points.;Timepoint(s) of evaluation of this end point: 52 weeks (end of trial) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1st key secondary - Whether or not the participant is a dose responder after 52 weeks of randomized treatment. A dose responder is a participant who: i) is receiving after 52 weeks of randomized treatment a total daily dose of hydrocortisone of not more than 25 mg, and ii) is in biochemical control at the 08:00 hours assessment after 52 weeks of randomized treatment (where in biochemical control is defined as both a 17-OHP concentration equal to or below the upper limit for optimal control and an A4 concentration equal to or below the upper limit of the reference range). The difference (Chronocort minus IRHC) between the proportion of participants in each treatment arm who are dose responders 52 weeks after randomization will be estimated in the FAS. Participants who die or withdraw from treatment before 52 weeks will be classified as not a dose responder. Participants receiving rescue medication under the 'stress dosing rules' within 5 days before the scheduled visit at 52 weeks after randomization will have their visit delayed appropriately1. Dose superiority of Chronocort to IRHC will be declared if the 95% CI for the difference in proportions lies wholly above zero, provided that biochemical non-inferiority of Chronocort to IRHC has been declared under the primary efficacy objective. The first key secondary null hypothesis is that the response rate in the Chronocort arm is worse than or equal to the response rate in the IRHC arm. The 2nd key secondary - The total daily dose (mg) after 52 weeks of randomized treatment. The difference (Chronocort minus IRHC) between the mean total daily dose after 52 weeks of randomized treatment in each treatment arm will be estimated in the FAS. Superiority of Chronocort to IRHC with respect to total daily dose after 52 weeks of randomized treatment will be declared if the 95% CI for the difference in means lies wholly below zero, provided that dose superiority of Chronocort to IRHC has been de | — |
Countries
France, Japan, Turkey, United States
Contacts
Public ContactClinical trial information
Diurnal Limited
Outcome results
None listed