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

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 AUC_0−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.