Relative Bioavailability of Once-Daily Clonidine XR Oral Suspension Versus Twice-Daily XR Tablets in Healthy Volunteers

Purpose: To assess the bioequivalence of once-daily clonidine extended-release (XR) oral suspension (OS) to twice-daily clonidine XR tablets (TABs), which are approved for attention-deficit/hyperactivity disorder (ADHD). Methods: Study 1 ( n = 20) evaluated an equivalent daily dose of clonidine XR OS versus TABs and clonidine XR OS under fed versus fasted conditions. Outcomes included the maximum plasma concentration (C max ), the area under the analyte versus time curve (AUC) from 0 to the last analyte concentration (AUC t ) and to infinity (AUC inf ), and the half-life (T half ). Study 2 ( n = 19) evaluated AUC, C max , and the minimum concentration (C min ) at steady state (SS). The ratios of geometric means and corresponding 90% CIs of pharmacokinetic parameters for each treatment were compared to the US Food and Drug Administration definition of bioequivalence (80%–125%). Results: In Study 1 (mean [ SD ] age, 42 [11] years; 30% female; 10% Asian, 25% Black or African American, 5% Multiracial, 60% White; 40% Hispanic or Latino), the ratios (90% CIs) of clonidine XR OS to TABs were within the bioequivalence range accepted by the FDA for C max (95.6 [89.8, 101.8]), AUC t (97.2 [91.6, 103.1]) and AUC inf (96.1 [89.4, 103.4]); similar results were observed for clonidine XR OS under fed versus fasting conditions. The median (range) T half was 12.8 (8–24) hours. In study 2 (mean [ SD ] age, 43 [11] years; 42% female; 47% Asian, 26% Black or African American, 0% Multiracial, 26% White; 0% Hispanic or Latino), AUC t,ss and C max,ss were both within the acceptable range (97.7 [93.4, 102.1] and 107.9 [103.8, 112.2], respectively). The C min,ss for clonidine XR OS was ~26% lower than clonidine XR TABs (74.0 [69.3, 79.0]) but this difference was not considered clinically meaningful by the FDA. Conclusion: These results demonstrate that clonidine XR OS is bioequivalent to clonidine XR TABs and could fulfill a treatment gap as a liquid, once-daily, non-stimulant ADHD treatment option.