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

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.

Inclusion:

- Nonsmoking male and female subjects, age >/= 18 to
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.