SUN-001 - Two-Arm Bioequivalence Study between 600 Mcg of Desmopressin Oral Solution (ET-600) and Desmopressin (DDAVP®) Tablets in Healthy Adults

Objective
Desmopressin oral solution (DOS) was developed to improve dosing accuracy and reduce complications associated with over- or underdosing of desmopressin (DM) in pediatric patients with arginine vasopressin deficiency (AVP-D). This study evaluated the bioequivalence of DOS compared with an FDA-approved oral DM formulation, desmopressin oral tablets (DOT).

Methods
This was a single-center, open-label, randomized, three-period, crossover, single-dose bioequivalence study conducted in healthy adult subjects. Treatments included 600 mcg DOS (fasted), 600 mcg DOS (fed), and 600 mcg DOT (fasted); results presented here focus on the fasted DOS versus fasted DOT comparison. Subjects fasted for ≥10 hours prior to dosing. Pharmacokinetic (PK) blood samples were collected over 18 hours post-dose. Subjects were randomized to receive a single 600 mcg dose of DOS or DOT, followed by the alternate treatment after a 14-day washout period. Water intake was restricted from 2 hours pre-dose to 8 hours post-dose, except for 240 ± 2 mL at dosing and at lunch. Bioequivalence was defined as 90% confidence intervals (CI) for baseline-adjusted AUCt, AUCinf, and Cmax within 80–125%.

Results
Seventy-five subjects were enrolled, and 67 completed the study; three subjects discontinued due to adverse events (AEs). Mean PK parameter ratios (DOS to DOT) were 103.7% for AUCt (282.15 vs 271.97 hr·pg/mL), 103.7% for AUCinf (291.83 vs 281.52 hr·pg/mL), and 101.9% for Cmax (77.30 vs 75.87 pg/mL). The PK profiles demonstrated comparable metabolic elimination over 18 hours, with no meaningful differences between formulations. Both treatments were generally well tolerated. Two cases of hyponatremia occurred following DOT administration, and one case of vomiting occurred following DOS administration. No serious AEs were reported, and no AEs compromised subject safety or study outcomes.

Conclusion
Desmopressin oral solution and desmopressin oral tablets are bioequivalent in healthy, fasted adult subjects. Both formulations were generally well tolerated, supporting the clinical comparability of DOS to the approved tablet formulation.

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