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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01308541
First received: March 2, 2011
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Monitored Anesthesia Care
Drug: arm 1
Drug: LUSEDRA
Drug: Propofol (arm 3)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Arterial plasma levels of fospropofol and propofol during each treatment: [ Time Frame: up to 480 minutes postdose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PD effect during each treatment measured by continuous BIS recordings [ Time Frame: up to 480 minutes postdose ] [ Designated as safety issue: No ]
  • PD effect during each treatment measured by sedation (MOAA/S) assessments [ Time Frame: up to 480 minutes postdose ] [ Designated as safety issue: No ]
  • Relationships between PK and PD of fospropofol and propofol will be explored using PK/PD modeling. [ Time Frame: up to 480 minutes postdose ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: January 2011
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: LUSEDRA (arm 1) 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.

Active Comparator: LUSEDRA (arm 2) 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.
Active Comparator: Propofol (arm 3) 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.

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01308541

Locations
United States, Utah
University of Utah
Salt Lake City Utah, Utah, United States, 84132Ut
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Talmage Egan Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01308541     History of Changes
Other Study ID Numbers: E2083-A001-006
Study First Received: March 2, 2011
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Propofol
Fospropofol disodium
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Hypnotics and Sedatives

ClinicalTrials.gov processed this record on April 17, 2014