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

November 2, 2015 updated by: Eisai Inc.

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

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.

Study Overview

Status

Completed

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.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Utah
      • Salt Lake City Utah, Utah, United States, 84132Ut
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: LUSEDRA (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.

ACTIVE_COMPARATOR: LUSEDRA (arm 2)
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.
ACTIVE_COMPARATOR: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Arterial plasma levels of fospropofol and propofol during each treatment:
Time Frame: up to 480 minutes postdose
up to 480 minutes postdose

Secondary Outcome Measures

Outcome Measure
Time Frame
PD effect during each treatment measured by continuous BIS recordings
Time Frame: up to 480 minutes postdose
up to 480 minutes postdose
PD effect during each treatment measured by sedation (MOAA/S) assessments
Time Frame: up to 480 minutes postdose
up to 480 minutes postdose
Relationships between PK and PD of fospropofol and propofol will be explored using PK/PD modeling.
Time Frame: up to 480 minutes postdose
up to 480 minutes postdose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Talmage Egan, Eisai Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (ACTUAL)

August 1, 2011

Study Completion (ACTUAL)

August 1, 2011

Study Registration Dates

First Submitted

March 2, 2011

First Submitted That Met QC Criteria

March 3, 2011

First Posted (ESTIMATE)

March 4, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

November 3, 2015

Last Update Submitted That Met QC Criteria

November 2, 2015

Last Verified

November 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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