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

Eisai

Status and phase

Completed

Phase 1

Conditions

Monitored Anesthesia Care

Treatments

Drug: arm 1

Drug: Propofol (arm 3)

Drug: LUSEDRA

Study type

Interventional

Funder types

Industry

Identifiers

NCT01308541

E2083-A001-006

Details and patient eligibility

About

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.

Full 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.

Enrollment

20 patients

Sex

All

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion:

Nonsmoking male and female subjects, age >/= 18 to </= 45 years old at Screening.

Exclusion:

Body mass index (BMI) >/= 30
Subjects who smoke or have used nicotine or nicotine-containing products within 18 months of Screening and throughout the study
Subjects with a known history of clinically significant drug or food allergies, including allergies to any ingredients in either medication (fospropofol disodium or propofol injectable emulsion) or presently experiencing significant seasonal allergy
Subjects who are allergic to eggs, egg products, soybeans, or soy products
Subjects having a past or current medical history of any respiratory illness including asthma or sleep apnea
Subjects with disorders of fat metabolism, or who are predisposed to fat embolism, or who have other conditions in which lipid emulsions must be used carefully
Subjects currently taking any medications including over-the-counter (OTC) medication (within 14 days prior to Baseline Period 1) with the exceptions of hormonal contraceptives and hormone replacement therapy, as long as the subject was on a stable dose of the same product for at least 12 weeks prior to dosing.
Use of 1.0% lidocaine <1.0 mL for placement of all arterial lines is allowed.