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

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).

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%).

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.

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.