Context: Alkindi® (Hydrocortisone Granules, Diurnal Ltd, UK), was recently licensed for oral administration to children with adrenal insufficiency (AI) from birth to 18 years. Previously, children received compounded hydrocortisone to achieve age appropriate dosing, however almost 25% of batches were out of specification for mass and content uniformity and clinically evident under- and over-dosing was reported.
Objectives: Primary: long-term safety of Alkindi®; Secondary: disease control in children on Alkindi®.
Patients & study design: Of the 24 children who completed the Alkindi® Phase 3 trial 18 children were enrolled in this extension study: 6 withdrew early; 1 subject spat out the first dose and was withdrawn from the study without further dosing, and the remaining 5 subjects withdrew due to local issues as their last dose was to be taken during the night. Median ages at entry were ~3.5 years in Cohort 1; ~2 years Cohort 2; and 46 days in Cohort 3. Follow-up included monthly visits for the first 2 months followed by 3 monthly thereafter. The results reflect the first planned data cut at one year of follow up.
Results: Children were compliant with treatment. Safety: No cases of adrenal crisis were reported. Between 4 and 9 subjects at each visit had implemented sick day rules in the preceding study period with the primary reason being fever. 80 treatment-emergent adverse events (TEAEs) were reported by 12 out of 18 subjects including viral upper respiratory tract infections, vomiting, and otitis media; typical illnesses seen in young children. There were no deaths, severe TEAEs, TEAEs leading to withdrawal from the study, and no TEAEs with a suspected causal relationship to Alkindi®. One SAE of moderate erysipelas (jellyfish sting) was reported. Efficacy: Cortisol levels remained above the baseline levels at most visits. All Tanner Development Stage assessments (breast, genitalia, and pubic hair) were Grade 1 (pre-pubertal) at baseline, with no progression seen. Z-scores for height and weight showed no trends for accelerated or reduced growth, during this first year of data collection.
Conclusions: Alkindi® was well tolerated with neither adrenal crisis nor AEs reported related to Alkindi® treatment. The most frequently reported AEs were infections, which were managed appropriately using sick day rules. There was no indication of either under-treatment or over-treatment, which is important for achievement of disease control in the growing child.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology