ESPE Abstracts

Introduction: Children with congenital adrenal hyperplasia (CAH) and adrenal insufficiency (AI) rely on lifelong hormone replacement with hydrocortisone (HC). Alkindi® is the first HC licensed for children from birth to 18 years with AI, available in small doses of 0.5, 1, 2 and 5mg required for the needs of neonates, infants and children.

Objectives: Primary: long-term safety of Alkindi®; Secondary: long-term disease control in children aged 0-6 years.

Methods: Of the 24 patients who completed the initial Phase 3 trial, 18 patients, aged 0-5 years, were enrolled in this long-term study (CAH, n=17; hypopituitarism, n=1). Median ages at entry were 3.6 years in cohort 1 (2- < 6 years in the initial trial, n=9), 2 years in cohort 2 (1 month- < 2 years in the initial trial, n=6) and 46 days in cohort 3 (<28 days in the initial trial, n=3). Ten subjects were male, all were white (Caucasian). Children were observed by two visits every month, followed up by 3 monthly visits thereafter. Therapy was controlled by routinely taken 17-OHP saliva sampling every three months starting from 3-6 months of age.

Results: Children were observed over >2 years (median 795 days (1-872 days)). Six, mainly older children, withdrew their consent due to personal reasons. All other children were compliant with treatment. Hydrocortisone granules (Alkindi®) were prescribed every 8 hours with a mean daily dose per BSA between 10.98 – 12.85 mg/m² in cohort 1, 9.17 – 10.64 mg/m² in cohort 2 and 10.46 – 17.52 mg/m² in cohort 3. All but one patient with panhypopituitarism received additional fludrocortisone therapy.

Safety: No cases of adrenal crisis and no AEs of choking. A total of 193 treatment-emergent adverse events (TEAEs) were reported by 14 subjects (77.8%) with the primary diagnosis being fever and viral upper respiratory tract infection. No deaths, severe TEAEs, TEAEs leading to withdrawal from the study and no TEAEs with a suspected causal relationship to Alkindi®. Nine serious adverse events (SAEs) were reported in three patients (gastroenteritis, vomiting, urinary tract infection, erysipelas), all of them considered not related to Alkindi®.

Efficacy: Standard deviation scores for height and weight showed no trends for accelerated or reduced growth.

Conclusions: During >2-year follow up of children aged 0-7 years, no AEs related to Alkindi® treatment and no adrenal crisis occurred. All children grew along their expected percentiles. Mean daily HC-dose controlled by routine saliva sampling was at the lower recommended dose-range.