Phase I Study Evaluating Safety, Pharmacokinetics, and Efficacy of a Combination Containing Ropivacaine, Clonidine, and Betamethasone (Ropiclobet, Batch:PL23001) for Sciatic Nerve Block in the Popliteal Region in Healthy Volunteers

This is a national, single-center, dose-escalation Phase I clinical study designed to evaluate the safety, pharmacokinetics, and efficacy of a novel combination drug containing Ropivacaine, Clonidine, and Betamethasone, referred to as Ropiclobet, in healthy adult volunteers. The primary objective is to assess the safety of Ropiclobet when administered as a sciatic nerve block in the popliteal region. Secondary objectives include monitoring the drug's efficacy in inducing motor and sensory nerve blockade and evaluating its pharmacokinetic profile through.

The study will begin with the enrollment of a minimum of 28 healthy volunteers who meet the predefined eligibility criteria. Once deemed eligible, participants will receive a sciatic nerve block in the popliteal region using the investigational combination drug Ropiclobet. To investigate the pharmacokinetics of Ropiclobet, blood samples will be collected from each volunteer at carefully scheduled time points post-administration. These samples will be analyzed to determine the plasma concentrations of the three active components: Ropivacaine, Clonidine, and Betamethasone. Concurrently, effects of the drug will be evaluated by monitoring motor and sensory nerve blockades, specifically targeting the two primary branches of the popliteal nerve: the tibial nerve and the common peroneal nerve. Sensory blockade assessments will include tests for pin-prick and temperature sensations, while motor block evaluation will involve standardized clinical examinations.

Throughout the study, comprehensive safety monitoring will be conducted. This includes regular physical examinations, continuous vital sign measurements, electrocardiograms (ECGs), and the assessment of sedation levels. Volunteers will remain under observation in the Phase I clinic for at least 48 hours post-procedure. Discharge from the clinic will only occur after confirmation that both motor and sensory blocks have fully resolved. If the blocks persist beyond the 48-hour observation window, participants will be discharged no later than six hours following the resolution of the blockades. In addition to in-clinic assessments, follow-up evaluations will be performed on Days 10 and 15 on an outpatient basis, with a comprehensive end-of-study visit scheduled for Day 30. These visits aim to identify any delayed adverse effects and to ensure the complete recovery of participants.

The study's dose-escalation protocol involves four predefined dose levels of Ropiclobet: 5 mL, 10 mL, 15 mL, and 20 mL. Initially, 4 volunteers will receive a 5 mL dose for the sciatic nerve block. After a 48-hour observation period, detailed safety assessments will determine whether it is safe to proceed to the next dose level. If the safety profile of the 5 mL dose is deemed acceptable, an additional 8 volunteers will receive a 10 mL dose. This stepwise approach will continue with escalating doses of 15 mL and 20 mL, with safety evaluations conducted at each level before advancing to the subsequent dose. The final dose of 20 mL will only be administered if safety parameters remain within acceptable limits throughout the study.