A Randomized, Open Label, Multiple-dose, Two-way Study to Evaluate Bioavailability of Clonidine HCl Extended-release Oral Suspension compared to Clonidine HCl Extended-release Tablets

Objective
The need for additional ADHD medication options as monotherapy or in combination with stimulants exists, as not all patients respond optimally to stimulants, which are often used as first-line therapies for ADHD. This randomized, open-label, multiple-dose, two-way study was conducted to evaluate the bioavailability of ONYDA XR (clonidine HCl extended-release oral suspension (EROS); Tris Pharma, Inc. Monmouth Junction, NJ) compared to clonidine ER tablets at steady state under fasting conditions.

Methods
Twenty healthy adult males and females were randomly assigned to receive 0.2mg clonidine HCl EROS (0.1mg/mL) once-daily in the evening for 5 days, or 0.2mg clonidine ER tablet administered in equal doses of 0.1mg tablet 12 hours apart for 5 days, with a 14-day washout between periods. Plasma concentrations of clonidine at selected time points were measured and pharmacokinetic parameters were determined.

Results
Nineteen healthy adult subjects completed the study with 20 included in the safety dataset. After administration of a 0.2mg dose of clonidine HCl EROS once daily over 5 days, the peak steady state plasma concentration (Cmax,ss) was 107.9% and steady state relative bioavailability (AUCt,ss) was 97.7% compared with clonidine ER tablet 0.1mg twice daily. Overall, the study medications were well tolerated without serious adverse events.

Conclusions
Clonidine HCl EROS 0.2mg once-daily exhibited equivalent peak and total exposure compared to clonidine ER tablet 0.1mg twice-daily for 5 days. Clonidine HCl EROS can potentially fill an important role providing a once-daily, oral suspension, non-stimulant option for the treatment of ADHD.