SAT-427 Bioequivalence Study between 5 mg of Hydrocortisone Solution (ET-400) versus Hydrocortisone Oral Granules (Alkindi Sprinkle)

Abstract Disclosure: B. Seo: Eton Pharmaceuticals. M.L. Freedman: Eton Pharmaceuticals. I. Hoos: Eton Pharmaceuticals. D. Radosavljevic: Eton Pharmaceuticals. A. Christensen: Eton Pharmaceuticals. Background: Treatment of adrenal insufficiency in children requires precise hydrocortisone (HC) dosing. Since the discontinuation of Cortef oral suspension, oral dosing options for this population are limited. Current Endocrine Society guidelines for primary adrenal insufficiency suggest dosing as low as 8 mg/m2/day split into 3 doses. The guidelines also recommend against using a compound pharmacy. Precise HC dosing is important because adverse outcomes including adrenal crisis can result from too little HC. Too high HC dosing can also cause detrimental effects, including Cushinoid sequela. An HC oral solution (HOS) was developed to assist with dosing accuracy in children to prevent complications that may arise from under- or overdoing of HC in pediatric, adrenal insufficient patients. Objective: This study investigated if a novel HOS is bioequivalent to a known, FDA-approved, oral HC formulation, also designed for pediatric patients, hydrocortisone oral granules (HOG). Methods: A single-center, open-label, randomized, two-period, crossover, single-dose, bioequivalency study between 5 mg HOS, 1 mg/mL, and 5 mg HOG in dexamethasone (DM)-suppressed healthy adults was conducted. Subjects were administered 4 mg DM 10 hr prior to HC administration. Subjects also fasted for 10 hr prior to HC administration. PK blood draws were conducted over 13 hr, beginning at 1 hr prior to HC administration. PK variables were determined for measured HC using a non-compartmental approach. Subjects were randomized to one of two conditions. Subjects were administered a single dose of 5 mg HOS or HOG. After a 7-day washout, subjects were administered the other treatment. The 2 HC formulations were considered bioequivalent if the 90% CI of the baseline adjusted HC AUCt, AUCinf, and Cmax were within 80 - 125%. Results: 36 subjects were recruited and enrolled in the study. 34 subjects completed the study. 2 subjects were discontinued because of an AE (fever and COVID-19 infection, respectively). The mean differences were: • * AUCt difference was 97.6% (390.7 vs 395.8 hr*ng/mL HOS to HOG, respectively) • * AUCinf difference was 99.4% (456.5 vs 455.8 hr*ng/mL HOS to HOG, respectively) • * Cmax difference was 104.7% (158.6 vs 152.8 ng/mL HOS to HOG, respectively) The study drugs were generally well-tolerated by the healthy DM-suppressed, fasted subjects. There were no serious AEs. None of the AEs compromised the subject’s safety or impacted the study results. Conclusion: This study confirms that HOS and HOG are bioequivalent in DM-suppressed, healthy, fasted adult subjects. Overall, the study medications were well tolerated in this population. Presentation: Saturday, July 12, 2025