Switching patients with congenital adrenal hyperplasia to modified-release hydrocortisone capsules: relative bioavailability and disease control
Author(s)
Ross, Richard John M
Arlt, Wiebke
de la Perriere, Aude Brac
Hirschberg, Angelica Linden
Juul, Anders
Type
Journal Article
Abstract
Background
Replacement therapy with modified-release hydrocortisone capsules (MRHC) restores the physiological circadian cortisol rhythm in congenital adrenal hyperplasia (CAH).
Aims
To determine the relative bioavailability of MRHC and evaluate an optimal protocol to switch CAH patients from standard therapy to MRHC.
Methods
(1): Crossover study in healthy participants comparing relative bioavailability of MRHC with immediate-release hydrocortisone (IRHC). (2): Post hoc analysis of first 4 weeks of phase 3 MRHC study when CAH patients were switched to MRHC.
Results
Twenty-four healthy male participants completed the relative bioavailability study: 20 mg MRHC showed comparable bioavailability to 20 mg IRHC tablets; mean AUC0−inf was 2650 versus 2450 h*nmol/L, ratio of 108% (90% confidence interval (CI) 103%−113%). In the phase 3 study, 122 CAH patients were recruited of which 63 patients were managed with IRHC alone at baseline; 31 of 63 were randomised to continue IRHC and 32 of 63 were randomised to switch to MRHC on the same daily dose but given twice daily. At 4 weeks, a greater reduction in both the 09:00 h 17-hydroxyprogesterone and androstenedione was observed in the MRHC group compared to the IRHC group; p < 0.001 and p = 0.01, respectively.
Conclusions
MRHC showed comparable bioavailability to IRHC based on cortisol AUC after 20 mg administration. Switching patients treated with IRHC to a twice daily MRHC regimen on the same daily dose (giving approximately two thirds of the dose at night) is an effective protocol for starting MRHC treatment.
Replacement therapy with modified-release hydrocortisone capsules (MRHC) restores the physiological circadian cortisol rhythm in congenital adrenal hyperplasia (CAH).
Aims
To determine the relative bioavailability of MRHC and evaluate an optimal protocol to switch CAH patients from standard therapy to MRHC.
Methods
(1): Crossover study in healthy participants comparing relative bioavailability of MRHC with immediate-release hydrocortisone (IRHC). (2): Post hoc analysis of first 4 weeks of phase 3 MRHC study when CAH patients were switched to MRHC.
Results
Twenty-four healthy male participants completed the relative bioavailability study: 20 mg MRHC showed comparable bioavailability to 20 mg IRHC tablets; mean AUC0−inf was 2650 versus 2450 h*nmol/L, ratio of 108% (90% confidence interval (CI) 103%−113%). In the phase 3 study, 122 CAH patients were recruited of which 63 patients were managed with IRHC alone at baseline; 31 of 63 were randomised to continue IRHC and 32 of 63 were randomised to switch to MRHC on the same daily dose but given twice daily. At 4 weeks, a greater reduction in both the 09:00 h 17-hydroxyprogesterone and androstenedione was observed in the MRHC group compared to the IRHC group; p < 0.001 and p = 0.01, respectively.
Conclusions
MRHC showed comparable bioavailability to IRHC based on cortisol AUC after 20 mg administration. Switching patients treated with IRHC to a twice daily MRHC regimen on the same daily dose (giving approximately two thirds of the dose at night) is an effective protocol for starting MRHC treatment.
Date Issued
2025-09-01
Date Acceptance
2025-05-08
Citation
Clinical Endocrinology, 2025, 103 (3), pp.290-293
ISSN
0300-0664
Publisher
Wiley
Start Page
290
End Page
293
Journal / Book Title
Clinical Endocrinology
Volume
103
Issue
3
Copyright Statement
© 2025 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40377230
Subjects
21-hydroxylase deficiency
adrenal insufficiency
congenital adrenal hyperplasia
CORTISOL
Endocrinology & Metabolism
glucocorticoid
hydrocortisone
Life Sciences & Biomedicine
MRHC
Science & Technology
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2025-05-16