# Switching Patients With Congenital Adrenal Hyperplasia to Modified‐Release Hydrocortisone Capsules: Relative Bioavailability and Disease Control

## TL;DR

A study shows that modified-release hydrocortisone capsules work as well as standard treatment for adrenal hyperplasia and improve disease control.

## Contribution

The study introduces a new protocol for switching patients to modified-release hydrocortisone capsules with improved disease control.

## Key findings

- Modified-release hydrocortisone capsules showed comparable bioavailability to immediate-release hydrocortisone.
- Switching patients to modified-release hydrocortisone capsules reduced hormone levels more effectively than standard treatment.

## Abstract

Replacement therapy with modified‐release hydrocortisone capsules (MRHC) restores the physiological circadian cortisol rhythm in congenital adrenal hyperplasia (CAH).

To determine the relative bioavailability of MRHC and evaluate an optimal protocol to switch CAH patients from standard therapy to MRHC.

(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.

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.

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.