Open-Label, Balanced, Randomized, Single-Dose, Three-Treatment, Three-Sequence, Three-Period, Three-Way Crossover...

Area of Science:

• Pharmacokinetics and Drug Bioequivalence
• Endocrinology and Metabolic Disorders
• Pharmaceutical Sciences

Background:

• Desmopressin acetate is a critical treatment for central diabetes insipidus (CDI), also known as arginine vasopressin deficiency.
• Dosing desmopressin presents challenges due to its narrow therapeutic index, necessitating precise formulations.
• Evaluating new formulations is essential for improving patient outcomes and therapeutic options.

Purpose of the Study:

• To assess the bioequivalence of a novel desmopressin acetate oral solution (50 mcg/mL) compared to conventional desmopressin acetate tablets (200 mcg).
• To provide pharmacokinetic data supporting the regulatory approval of the desmopressin oral solution.

Main Methods:

• An open-label, randomized, three-way crossover study involving 75 healthy adults.
• Administration of a single 600-mcg dose of test (oral solution) and reference (tablet) products under fasted conditions.
• Measurement of plasma desmopressin concentrations using LC-ESI-MS/MS, with analysis of Cmax, AUC0-t, and AUC0-∞.

Main Results:

• The desmopressin oral solution demonstrated bioequivalence to the tablets, with geometric mean ratios within the 80%-125% acceptance range.
• Key pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞) confirmed comparable absorption profiles between the two formulations.
• Both formulations showed similar median time to maximum concentration (1.0 h) and mean elimination half-life (~3.6 h).

Conclusions:

• The desmopressin acetate oral solution is bioequivalent to the desmopressin acetate tablet formulation.
• This establishes the oral solution as a viable alternative for desmopressin therapy, potentially offering improved dosing flexibility.
• The findings support the regulatory approval and clinical use of the desmopressin acetate oral solution.