Endocrine Abstracts (2018) 58 OC4.1 | DOI: 10.1530/endoabs.58.OC4.1

Hydrocortisone granules in capsules for opening: phase 3 trial in children with adrenal insufficiency and long-term safety data

Alexander Lewis2, Uta Neumann1, Susanna Wiegand1, Heiko Krude1, Dina Digweed2, Bernard Voet2, Richard Ross3, Madhu Davies2 & Oliver Blankenstein1

1Institute for Experimental Paediatric Endocrinology, Charite Universitatsmedizin Berlin Campus Virchow-Klinikum, Berlin, Germany; 2Diurnal Ltd., Cardiff, UK; 3Department of Endocrinology, The University of Sheffield, The Medical School, Sheffield, UK.

Introduction: Children with adrenal insufficiency requiring hydrocortisone rely on compounded adult medication. This study aimed to evaluate the absorption, palatability and safety of Alkindi® (hydrocortisone granules in capsules for opening).

Methods: The phase 3 study was an open-label, single-dose study in a total of 24 children (aged 0–6 years) with adrenal insufficiency. Fasted children were given a single dose of Alkindi® as dry granules administered directly from capsule or spoon followed by a drink. The primary endpoint was serum cortisol concentration 60 min after administration. Secondary endpoints were palatability and adverse events.

Results: All children showed an increase in cortisol above baseline after administration of Alkindi® (P<0.0001), with geometric mean ±S.D. cortisol concentration at 60 min of 575.8±299.5 nmol/l. There were no difficulties with administration and 95.5% of parents/carers reported they preferred Alkindi® over their child’s current medication. Six children completed an age-appropriate palatability questionnaire: 80% responses were very good, good, or neutral and 20% were bad or very bad. No serious or severe treatment-emergent adverse events were reported. Subjects were invited to continue to receive Alkindi in an ongoing extension study, in which Alkindi was administered at home, according to usual clinical practice (three times per day). The primary endpoint was safety. Interim analysis up to 12 months reported 80 Treatment Emergent Adverse Events, all typical illnesses in young children, and none suspected to be related to Alkindi. One SAE of moderate erysipelas was reported and successfully managed with stress dosing of Alkindi. No cases of choking or adrenal crises have been reported to date. Cortisol levels remained above baseline at most visits. All Tanner developmental stage assessments remained at grade 1. Z scores for height and weight showed no trends for accelerated or reduced growth.

Conclusions: Alkindi is well tolerated, easy to administer, and produces cortisol levels similar to those reported in healthy children. In an extension study, no adverse events were suspected to be related to Alkindi, and no adrenal crises have been reported.