Abstract Body: Introduction/Background: Clonidine is a centrally acting alpha-agonist indicated to treat hypertension; it is typically administered as a tablet formulation. About one-third of adult primary care patients have difficulty swallowing tablets or capsules. A ready-to-use clonidine oral solution (COS) may provide an alternative for patients who have difficulty swallowing solid oral dosage forms.
Research Questions/Hypothesis: To determine whether COS (supplied as 0.02 mg/mL) is bioequivalent (BE) to a conventional clonidine tablet (CT) and whether food affects exposure.
Goals/Aims: Characterization of the PK profile of COS (at a dose of 0.3 mg in 15 mL) vs CT (0.3 mg) after a single oral dose and evaluation of the effects of food.
Methods/Approach: Healthy, adult, volunteers 18-45 years old with a BMI of 18.5-30.0 kg/m² were enrolled in an open-label, balanced, randomized, single-dose, three-treatment (CT or COS after a 10-hour fast, COS after a high-fat 800-1,000 calorie breakfast), three-period cross-over study with 7-day washouts between periods. Blood samples were collected before and up to 96 hours after each dose. Quantification of clonidine concentrations in plasma was done using LC-ESI-MS/MS; PK parameters were determined using a non-compartment model. The acceptance range for BE was 80%-125% for 90% CIs of the geometric LSM ratio for the ln-transformed PK parameters C_max, AUC_0-t, and AUC_0-∞. Ratios between fasted and fed conditions for COS within 80% to 125% were interpreted as no food effect.
Results/Data: A total of 36 subjects (23 males/13 females) were enrolled; 35 completed the study and contributed to the PK analysis (Table 1). The 90% CIs for the geometric LSM ratios (COS/CT) fell within the acceptance BE range for all primary PK endpoints, and fed/fasted comparisons similarly met criteria, indicating no food effect. Overall, COS and CT were well tolerated and had no safety concerns throughout the study period.
Conclusions: A ready-to-use COS was BE to conventional CT under fasting conditions. No clinically meaningful food effect on COS exposure was observed. These findings support the COS as a pharmacokinetically equivalent option for patients who require or may prefer a liquid formulation.