Infacort®, Oral Hydrocortisone Granules with Taste Masking for the Treatment of Neonates and Infants with Adrenal Insufficiency

Background: Current treatment for adrenal insufficiency in neonates and infants is unsatisfactory as unlicensed adult formulations are used and the minimum unit dose available is a scored 5mg hydrocortisone tablet.  These are difficult to administer to neonates and give rise to inconsistencies in dose as content uniformity of crushed tablets cannot be verified. We have developed a new formulation, Infacort®, specifically designed for infants and neonates, and present results of an adult phase 1 study.

Methods: Infacort®is an immediate release formulation of hydrocortisone that is provided in capsules containing multi-particulate granules at appropriate doses of 0.5, 1, 2 & 5 mg. The granules are designed with a taste masking layer to permit compliant oral dosing. This study evaluated the pharmacokinetic performance of Infacort® and its safety.  Infacort® was compared to 10 mg adult immediate-release hydrocortisone tablets in an open-label, randomised crossover study in 16 dexamethasone suppressed healthy adults.

Results: The pharmacokinetic results for 10mg Infacort® vs 10mg hydrocortisone immediate release were: Cmax  LSmean 566 vs 598 nmol/l, ratio Infacort® to hydrocortisone (90% CI),  95 (84-107); AUC_0-inf  LSmean 1602 vs 1576 hr*nmol/l, ratio Infacort® to hydrocortisone (90% CI), 101 (96-107); Tmax LSmean 0.75 vs 1.00 hr, mean difference Infacort® to hydrocortisone (95% CI), 0.0 (-0.5-0.3). Infacort® & hydrocortisone at a dose of 10 mg were bioequivalent, as reflected by geometric LSmean 90 % CI for ratios of Cmax, AUC0-t and AUC0-inf within 0.8 – 1.25. Infacort® was tested for dose-proportionality between 0.5 mg – 10 mg; Cmax, AUC0-t and AUC0-inf were shown to increase in a linear fashion and were dose-proportional when adjusted for protein binding. The majority of subjects described Infacort® as, “not good or bad”, for smell (81.3% to 87.5 % of subjects), feel in the mouth (68.8 % of subjects) and taste (68.8 % to 81.3 % of subjects).

Conclusions: Infacort® was safe, well tolerated and of neutral taste when administered as a single oral dose of 10 mg. Infacort® granules and hydrocortisone tablets were bioequivalent with respect to C_max, AUC and  t_max and demonstrated dose-proportionality.  Infacort® provides a new formulation specifically designed for the treatment of infants and neonates with adrenal insufficiency.