The goal of this clinical trial is to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of remimazolam (CNS 70754) in healthy adult participants. The main questions it aims to answer are: What are the key pharmacokinetic parameters of remimazolam, including peak concentration (Cmax), time to peak concentration (Tmax), area under the curve (AUC), and elimination half-life (T1/2)? What is the effect of remimazolam on consciousness, as measured by the MOAA/S scale and Narcotrend monitoring during anesthesia? Researchers will compare the pharmacokinetic and pharmacodynamic effects of remimazolam to see if the drug provides consistent and predictable sedation without significant adverse effects. Participants will: Receive continuous Infusion of Remimazolam. Have blood samples taken at various time points to measure plasma concentrations and calculate PK parameters. Be monitored for consciousness and sedation levels using the MOAA/S scale and Narcotrend. Undergo safety assessments, including laboratory tests, vital signs monitoring, and physical examinations throughout the study. This study will help determine the drug's behavior in the body and its impact on sedation, providing valuable information for its future clinical use in anesthesia and other medical applications. Last updated on December 22, 2024
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
This is the first clinical trial evaluating Remimazolam's pharmacokinetics (PK), pharmacodynamics (PD), and safety in renal transplant recipients-a population with unique physiological alterations due to end-stage renal disease and graft reperfusion. Key differentiators include: Population-Specific Dosing Protocol: Induction: 6 mg/kg/h until MOAA/S ≤1 (vs. 5-12 mg/kg/h in general surgery). Maintenance: Titrated (0.5-2 mg/kg/h) to Narcotrend Index 27-60 (lower than typical BIS 40-60 targets), accounting for altered drug metabolism post-transplant. Transplant-Specific Context: Administered alongside standard immunosuppressants (methylprednisolone 750 mg + furosemide 60 mg at reperfusion) but prohibits common sedatives (midazolam/propofol) to isolate Remimazolam's effects. PK/PD sampling accounts for graft function dynamics (e.g., blood draws during reperfusion and post-op days 1-6). Exploratory Genetic Analysis: First study linking VDR/
Shandong First Medical University Hospital
Jinan, Shangdong, China
RECRUITINGRemimazolam Plasma Concentration
Blood concentration (ng/mL) of Remimazolam
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.
Remimazolam PK Parameters
Maximum Plasma Concentration
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.
Remimazolam PK Parameters
Area Under the Curve (0 to last measurable t)
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes
Remimazolam PK Parameters
Area Under the Curve (0 to infinity)
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes
Remimazolam PK Parameters
Time to Cmax
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes
Remimazolam PK Parameters
Terminal Elimination Half-Life
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes
Remimazolam PK Parameters
Total Body Clearance
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes
Remimazolam PK Parameters
Renal Clearance
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes
Remimazolam PK Parameters
Apparent Volume of Distribution (Terminal)
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes
Remimazolam PK Parameters
Mean Residence Time
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes
Remimazolam PK Parameters
Percentage of AUC Extrapolated
Time frame: Pre-infusion, 2/5/10/20/30/45/60/120 minutes , hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes
CNS 7054 (Metabolite) PK Parameters
Maximum Plasma Concentration
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.
CNS 7054 (Metabolite) PK Parameters
Area Under the Curve (0 to last measurable t)
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.
CNS 7054 (Metabolite) PK Parameters
Area Under the Curve (0 to infinity)
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.
CNS 7054 (Metabolite) PK Parameters
Time to Cmax
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.
CNS 7054 (Metabolite) PK Parameters
Terminal Elimination Half-Life
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.
CNS 7054 (Metabolite) PK Parameters
Mean Residence Time
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.
CNS 7054 (Metabolite) PK Parameters
Percentage of AUC Extrapolated
Time frame: During surgery: Pre-infusion, 2/5/10/20/30/45/60/120 minutes, hourly until infusion stop; Post-infusion: 0/5/15/30/60/90/120/240 minutes.
Sedation Depth (PD)
MOAA/S score (0 to 5) + Narcotrend Index (NCI 0 to 100)
Time frame: Induction: every 1minutes until MOAA/S≤1; Maintenance: every 10 minutes; Recovery: every 2 minutes until 3 consecutive MOAA/S=5.
Time to Loss of Consciousness (MOAA/S ≤1)
Time from infusion start to first MOAA/S score ≤1
Time frame: 0 to 10 minutes after infusion start
Time to Full Alertness (3 consecutive MOAA/S=5)
Time from infusion stop to sustained alertness
Time frame: Time from infusion stop to sustained alertness
Narcotrend Index (NCI) Values
Anesthesia depth index (0-100 scale)
Time frame: Continuous monitoring during infusion + 30 min post-stop
Postoperative Urine Output
24-hour urine volume
Time frame: Postoperation Days 1 to 6
Serum Creatinine Level
Blood creatinine concentration
Time frame: Preoperation, Postoperation Days 1 to 6
Estimated Glomerular Filtration Rate
Kidney filtration rate
Time frame: Preoperation, Postoperation Days 1 to 6
Intraoperative Hypotension Incidence
MAP \<65 mmHg for \>1 minute
Time frame: Intra-operative period
Intraoperative Bradycardia Incidence
HR \<45 bpm for \>1 min
Time frame: Intra-operative period
Injection Pain Incidence
Participant-reported pain during drug administration
Time frame: During induction (0 to 10 minutes)
Postoperative Nausea/Vomiting Incidence
Postoperative Nausea/Vomiting occurrence
Time frame: PACU admission to Postoperation Day 6
Postoperative Agitation Incidence
RASS score ≥2
Time frame: PACU stay (0 to 2 hours)
Delayed Recovery Incidence
Extubation time \>30 min post-surgery
Time frame: End of surgery to PACU discharge
Intraoperative Awareness Incidence
Positive Brice questionnaire response
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Upon PACU discharge (Day 1)