NCT01308541

A Study to Characterize Pharmacokinetics (PK) and Pharmacodynamics (PD) of LUSEDRA® Administered as Continuous Infusion or Bolus Compared With Continuous Infusion of Propofol Injectable Emulsion

A Randomized, Open-label, 3 Period Crossover Study to Characterize the Pharmacokinetics and Pharmacodynamics of LUSEDRA (Fospropofol Disodium) Injection Administered Either by Continuous Infusion or Bolus Compared With Continuous Infusion of Propofol Injectable Emulsion

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Eisai Inc. · Industry
• Sex: All
• Age: —
• Healthy volunteers: Accepted

Summary

The purpose of this study is to explore the pharmacokinetics (PK) and pharmacodynamics (PD) of LUSEDRA® administered as a continuous infusion or bolus compared with continuous infusion of propofol injectable emulsion.

Detailed description

The study is designed to explore the pharmacokinetics (PK) and the pharmacokinetic/ pharmacodynamic (PK/PD) relationship between PK-Bispectral Index (BIS) and PK-Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores following administration of LUSEDRA, administered as a bolus or by continuous infusion, with that of propofol injectable emulsion administered by continuous infusion, using compartmental modeling. The clinical practice of sedation spans an entire continuum of sedation, only a portion of which is currently addressed by the currently approved dose which is intended to provide a moderate level of sedation. Another goal of the current study is to support potential follow-up indications for fospropofol disodium, such as prolonged sedation in the Intensive Care Unit (ICU) and induction and maintenance of general anesthesia, which require higher doses. If successful, the data from this study would allow a direct comparison of propofol doses, delivered as fospropofol disodium or as propofol injectable emulsion, that provide the same sedation effect and directly compare concentration-effect relations of propofol liberated from fospropofol disodium with that delivered as propofol. The doses and infusion times for fospropofol disodium and propofol in this study were selected based on simulation results using an established PK/PD model developed from historical data. Data collected in the current study will be used to further refine the existing PK/PD model. To enhance the robustness of that model, the study design includes changes in dose over the duration of sedation in the three treatment groups.

Conditions

• Monitored Anesthesia Care

Interventions

Type	Name	Description
DRUG	arm 1	Bolus Dose: two bolus doses of 15.0 mg/kg (first dose) and 8.0 mg/kg (second dose), 40 minutes apart. Continuous Infusion Dose: Total dose of 42.0 mg/kg administered over 3 hours at an infusion rate of 0.40 mg/kg/min for 1 hour, followed by 0.20 mg/kg/min for 1 hour, followed by 0.10 mg/kg/min for 1 hour.
DRUG	LUSEDRA	Mode of administration: intravenous (IV).Continuous Infusion Dose: Total dose of 42.0 mg/kg administered over 3 hours at an infusion rate of 0.40 mg/kg/min for 1 hour, followed by 0.20 mg/kg/min for 1 hour, followed by 0.10 mg/kg/min for 1 hour.
DRUG	Propofol (arm 3)	Mode of administration: intravenous (IV). A loading dose administered at a constant infusion rate of 0.20 mg/kg/min (0.50 mL/kg/min) for 10 minutes, followed by a constant-rate 2-hour infusion at 0.10 mg/kg/min; total dose infused over 130 minutes is 14.0 mg/kg.

Timeline

• Start date: 2011-01-01
• Primary completion: 2011-08-01
• Completion: 2011-08-01
• First posted: 2011-03-04
• Last updated: 2015-11-03

Locations

1 site across 1 country: United States