Page last updated: 2024-12-10

fospropofol

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Cross-References

ID SourceID
PubMed CID3038498
CHEMBL ID1201766
CHEBI ID135193
SCHEMBL ID3821874
MeSH IDM0583186

Synonyms (18)

Synonym
CHEBI:135193
fospropofol
DB06716
[2,6-di(propan-2-yl)phenoxy]methyl dihydrogen phosphate
CHEMBL1201766
unii-lz257rzp7k
methanol, (2,6-bis(1-methylethyl)phenoxy)-, dihydrogen phosphate
lz257rzp7k ,
fospropofol [inn]
258516-89-1
fospropofol [mi]
fospropofol [who-dd]
fospropofol [vandf]
gtpl7475
SCHEMBL3821874
FT-0727559
DTXSID50870295
Q5473368

Research Excerpts

Overview

Fospropofol is a water-soluble prodrug of propofol, a potent sedative-hypnotic agent. It is FDA-approved for monitored anesthesia care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures.

ExcerptReferenceRelevance
"FospropofolFD is a water-soluble prodrug of propofol."( Efficacy and Safety of FospropofolFD Compared to Propofol When Given During the Induction of General Anaesthesia: A Phase II, Multi-centre, Randomized, Parallel-Group, Active-Controlled, Double-Blind, Double-Dummy Study.
Li, Y; Liu, J; Liu, R; Luo, C; Xu, J; Zhang, W, 2016
)
1.47
"Fospropofol disodium is a water-soluble prodrug of propofol with unique pharmacokinetic/pharmacodynamic properties. "( A phase 3, randomized, double-blind study to assess the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy.
Downie, GH; Hansbrough, JR; Robinette, E; Silvestri, GA; Vincent, BD; Wahidi, MM, 2009
)
2.02
"Fospropofol is an aqueous solution of a propofol prodrug intended for injection."( New drug, fospropofol disodium: a propofol prodrug.
Rugari, SM; Welliver, M, 2009
)
1.48
"Fospropofol is a water-soluble prodrug of propofol, a potent sedative-hypnotic agent. "( Fospropofol: a new sedative-hypnotic agent for monitored anesthesia care.
MacLaren, R; Moore, GD; Walker, AM, 2009
)
3.24
"Fospropofol is a viable addition to the class of sedative-hypnotic agents due to the minimization of unwanted adverse effects of propofol and maintenance of a favorable pharmacokinetic profile facilitating sedation, anxiolysis, and rapid recovery. "( Fospropofol: a new sedative-hypnotic agent for monitored anesthesia care.
MacLaren, R; Moore, GD; Walker, AM, 2009
)
3.24
"Fospropofol is an intravenous sedative-anesthetic agent that is FDA-approved for monitored anesthesia care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures. "( Fospropofol, a new sedative anesthetic, and its utility in the perioperative period.
Abdelmalak, B; Khanna, A; Tetzlaff, J, 2012
)
3.26
"Fospropofol is a sedative hypnotic with a slower onset and longer duration of action. "( A double-blind, randomized, multicenter, dose-ranging study to evaluate the safety and efficacy of fospropofol disodium as an intravenous sedative for colonoscopy in high-risk populations.
Bergese, SD; Candiotti, K; Cohen, L; Dalal, P; Gan, TJ; Lin, Z; Satlin, A; Vandse, R,
)
1.79

Effects

Fospropofol Disodium has a protective effect on rat livers against ischemia-reperfusion injury, which is related with antioxidation. Fosprop ofol has a unique dosing regimen, with a standard dose for adults 18-65 years of age, and a modified dose (75% of the standard dose) for patients > 65.

ExcerptReferenceRelevance
"Fospropofol Disodium has a protective effect on rat livers against ischemia-reperfusion injury, which is related with antioxidation."( [Protective effect of fospropofol disodium on in vivo liver ischemia-reperfusion injury in rats].
Liu, Y; Luo, CZ, 2011
)
2.13
"Fospropofol has a unique dosing regimen, with a standard dose for adults 18-65 years of age, and a modified dose (75% of the standard dose) for patients > 65 years of age and for sicker adult patients whose American Society of Anesthesiologists physical status score is ≥ 3."( Fospropofol, a new sedative anesthetic, and its utility in the perioperative period.
Abdelmalak, B; Khanna, A; Tetzlaff, J, 2012
)
2.54
"Fospropofol Disodium has a protective effect on rat livers against ischemia-reperfusion injury, which is related with antioxidation."( [Protective effect of fospropofol disodium on in vivo liver ischemia-reperfusion injury in rats].
Liu, Y; Luo, CZ, 2011
)
2.13
"Fospropofol has a unique dosing regimen, with a standard dose for adults 18-65 years of age, and a modified dose (75% of the standard dose) for patients > 65 years of age and for sicker adult patients whose American Society of Anesthesiologists physical status score is ≥ 3."( Fospropofol, a new sedative anesthetic, and its utility in the perioperative period.
Abdelmalak, B; Khanna, A; Tetzlaff, J, 2012
)
2.54
"Fospropofol has demonstrated successful dose-dependent sedation at 6.5 mg/kg."( A double-blind, randomized, multicenter, dose-ranging study to evaluate the safety and efficacy of fospropofol disodium as an intravenous sedative for colonoscopy in high-risk populations.
Bergese, SD; Candiotti, K; Cohen, L; Dalal, P; Gan, TJ; Lin, Z; Satlin, A; Vandse, R,
)
1.07

Toxicity

Fospropofol provided safe and effective sedation for patients undergoing flexible bronchoscopy. Only treatment-related adverse event was a transient burning sensation in the perineal and perianal region during induction of sedation or anesthesia.

ExcerptReferenceRelevance
" The most frequent adverse events (AEs) were transient and self-limited paresthesias and pruritus of mild-to-moderate severity."( A phase 3, randomized, double-blind study to assess the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy.
Downie, GH; Hansbrough, JR; Robinette, E; Silvestri, GA; Vincent, BD; Wahidi, MM, 2009
)
0.58
"Fospropofol provided safe and effective sedation for patients undergoing flexible bronchoscopy."( A phase 3, randomized, double-blind study to assess the efficacy and safety of fospropofol disodium injection for moderate sedation in patients undergoing flexible bronchoscopy.
Downie, GH; Hansbrough, JR; Robinette, E; Silvestri, GA; Vincent, BD; Wahidi, MM, 2009
)
2.02
"Study endpoints included measures of sedation depth, requirement for supplemental sedative doses, use of alternative sedatives, and the frequency and nature of treatment-emergent and sedative-related adverse events."( Safety evaluation of fospropofol for sedation during minor surgical procedures.
Berry, BD; Ekman, EF; Gan, TJ; Hardi, R; Muckerman, RC; Shore, N, 2010
)
0.68
" The most common treatment-related adverse events (TRAEs) were self-limited: paresthesias (62."( Safety evaluation of fospropofol for sedation during minor surgical procedures.
Berry, BD; Ekman, EF; Gan, TJ; Hardi, R; Muckerman, RC; Shore, N, 2010
)
0.68
"5 mg/kg with supplemental doses was safe and well-tolerated as moderate sedation for use in minor surgical procedures."( Safety evaluation of fospropofol for sedation during minor surgical procedures.
Berry, BD; Ekman, EF; Gan, TJ; Hardi, R; Muckerman, RC; Shore, N, 2010
)
0.68
" Because incidence rates for adverse events were similar between fospropofol groups, and because the study was not powered to determine significant differences between treatment groups for safety variables, adverse events for both fospropofol groups were combined."( A randomized, open-label study of the safety and tolerability of fospropofol for patients requiring intubation and mechanical ventilation in the intensive care unit.
Bekker, A; Candiotti, KA; Gan, TJ; Kahn, R; Lebowitz, P; Littman, JJ; Sum-Ping, ST; Young, C, 2011
)
0.84
" There was a decreased need for alternative sedatives in subgroups 1 and 3 and fewer sedation- and treatment-emergent adverse events in all the subgroups for the approved dose."( A double-blind, randomized, multicenter, dose-ranging study to evaluate the safety and efficacy of fospropofol disodium as an intravenous sedative for colonoscopy in high-risk populations.
Bergese, SD; Candiotti, K; Cohen, L; Dalal, P; Gan, TJ; Lin, Z; Satlin, A; Vandse, R,
)
0.35
" Safety and tolerability were assessed by adverse events, neurologic examinations, clinical laboratory tests, and vital signs."( A randomized open-label phase I pilot study of the safety and efficacy of total intravenous anesthesia with fospropofol for coronary artery bypass graft surgery.
Fechner, J; Ihmsen, H; Jeleazcov, C; Schüttler, J, 2013
)
0.6
" The only treatment-related adverse event after administration of fospropofol was a transient burning sensation in the perineal and perianal region during induction of sedation or anesthesia."( A randomized open-label phase I pilot study of the safety and efficacy of total intravenous anesthesia with fospropofol for coronary artery bypass graft surgery.
Fechner, J; Ihmsen, H; Jeleazcov, C; Schüttler, J, 2013
)
0.84
"HX0969w, fospropofol disodium and propofol emulsion can produce sedative-hypnotic effects and they are safe when administered by oral route."( [The sedative-hypnotic effects and safety of oral administrated propofol prodrugs hx0969w and fospropofol disodiun in comparison with propofol emulsion in rats].
Wang, HY; Yang, J; Yang, LH; Yin, W; Zhang, WS, 2015
)
1.05
" No serious adverse events were observed in the two groups."( Efficacy and Safety of FospropofolFD Compared to Propofol When Given During the Induction of General Anaesthesia: A Phase II, Multi-centre, Randomized, Parallel-Group, Active-Controlled, Double-Blind, Double-Dummy Study.
Li, Y; Liu, J; Liu, R; Luo, C; Xu, J; Zhang, W, 2016
)
0.74

Pharmacokinetics

ExcerptReferenceRelevance
" GPI 15715 showed a short half-life (2."( Pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 in rats.
Burak, E; Fechner, J; Ihmsen, H; Schwilden, H; Schywalsky, M; Tzabazis, A; Vornov, J, 2003
)
0.32
" Pharmacokinetic simulations showed a longer time to peak propofol concentration after a bolus dose and a longer context-sensitive half-time."( Pharmacokinetics and clinical pharmacodynamics of the new propofol prodrug GPI 15715 in volunteers.
Burak, E; Fechner, J; Hatterscheid, D; Ihmsen, H; Schiessl, C; Schüttler, J; Schwilden, H; Vornov, JJ, 2003
)
0.32
" The pharmacodynamic effect was measured by the median frequency of the power spectrum of the electroencephalogram, and a sigmoid model with effect compartment was fitted to the data."( Comparative pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 and propofol emulsion.
Fechner, J; Hatterscheid, D; Ihmsen, H; Jeleazcov, C; Schiessl, C; Schüttler, J; Schwilden, H; Vornov, JJ, 2004
)
0.32
" Noncompartmental pharmacokinetic analyses were performed for all analytes."( AQUAVAN injection, a water-soluble prodrug of propofol, as a bolus injection: a phase I dose-escalation comparison with DIPRIVAN (part 1): pharmacokinetics.
Burak, E; Gibiansky, E; Gibiansky, L; Mortier, EP; Struys, MM; Van Bortel, L; Vanluchene, AL; Vornov, J, 2005
)
0.33
"The noncompartmental pharmacokinetic comparison revealed different dispositions of PropofolGPI and PropofolD."( AQUAVAN injection, a water-soluble prodrug of propofol, as a bolus injection: a phase I dose-escalation comparison with DIPRIVAN (part 1): pharmacokinetics.
Burak, E; Gibiansky, E; Gibiansky, L; Mortier, EP; Struys, MM; Van Bortel, L; Vanluchene, AL; Vornov, J, 2005
)
0.33
" The AQ combined pharmacokinetic-pharmacodynamic profile was best described by a nonlinear, six-compartment pharmacokinetic model and an effect site compartment."( AQUAVAN injection, a water-soluble prodrug of propofol, as a bolus injection: a phase I dose-escalation comparison with DIPRIVAN (part 2): pharmacodynamics and safety.
Gibiansky, E; Gibiansky, L; Mortier, EP; Struys, MM; Van Bortel, L; Vanluchene, AL; Vornov, J, 2005
)
0.33
" The pharmacokinetics of GPI 15715 or fospropofol could be described by a combined pharmacokinetic model with a submodel of two compartments for GPI 15715 and of three compartments for propofol(G)."( Pharmacokinetics and pharmacodynamics of GPI 15715 or fospropofol (Aquavan injection) - a water-soluble propofol prodrug.
Fechner, J; Schüttler, J; Schwilden, H, 2008
)
0.87
" Blood propofol followed three-compartment pharmacokinetic behavior and derived parameters were not statistically different except for elimination half-life from the CDP formulation and onset, and duration of anesthesia from the FP formulation."( Comparative canine pharmacokinetics-pharmacodynamics of fospropofol disodium injection, propofol emulsion, and cyclodextrin-enabled propofol solution following bolus parenteral administration.
McIntosh, MP; Rajewski, RA, 2012
)
0.63

Bioavailability

In rats, bioavailability of propofol from fospropofol delivered orally was found to be appreciable, in the order of around 20-70%, depending on dose.

ExcerptReferenceRelevance
" The purpose of the studies described here was to evaluate, in both animals and human volunteers, whether fospropofol (a water soluble phosphate ester prodrug of propofol) would provide higher propofol bioavailability through non-intravenous routes."( Gastrointestinal delivery of propofol from fospropofol: its bioavailability and activity in rodents and human volunteers.
Mistry, BM; Rais, R; Slusher, BS; Vornov, JJ; Wozniak, KM; Wu, Y, 2015
)
0.89
"In rats, bioavailability of propofol from fospropofol delivered orally was found to be appreciable, in the order of around 20-70%, depending on dose."( Gastrointestinal delivery of propofol from fospropofol: its bioavailability and activity in rodents and human volunteers.
Mistry, BM; Rais, R; Slusher, BS; Vornov, JJ; Wozniak, KM; Wu, Y, 2015
)
0.94

Dosage Studied

Fospropofol has a unique dosing regimen, with a standard dose for adults 18-65 years of age and a modified dose (75% of the standard dose) for patients > 65. The 5-mg/kg dose was associated with higher rates of sedation success, memory retention, and physician satisfaction.

ExcerptRelevanceReference
"Because propofol is the sedative preferred by gastroenterologists, we focus this review on gastroenterologist-directed propofol sedation, provide simulations of the respiratory depressant effect of different dosing protocols and give a perspective on future developments in computer-assisted sedation techniques."( Anesthesia or sedation for gastroenterologic endoscopies.
Luginbühl, M; Schumacher, P; Stüber, F; Vuilleumier, P, 2009
)
0.35
" Our simulations show that dosing protocols with small boluses administered at reasonable intervals induce less respiratory depression than large boluses."( Anesthesia or sedation for gastroenterologic endoscopies.
Luginbühl, M; Schumacher, P; Stüber, F; Vuilleumier, P, 2009
)
0.35
"5-mg/kg dosing regimen was well tolerated and effective for sedation during colonoscopy and was associated with higher rates of sedation success, memory retention, and physician satisfaction than the fospropofol 2-mg/kg dose."( A randomized, double-blind, phase 3 study of fospropofol disodium for sedation during colonoscopy.
Cattau, E; Cohen, LB; Goetsch, A; Kline, JM; Rex, DK; Shah, A; Weber, JR,
)
0.58
" In the three models, dose-response curves were established and their respective ED50 (50% effective dose) values were determined separately for each agent."( Synergistic antinociceptive interactions between fospropofol and alfentanil in mice.
Cao, S; Cui, J; Jia, N; Li, R; Li, Y; Wang, C; Wang, L; Wen, A; Wu, Y; Zhao, C, 2015
)
0.67
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
alkylbenzeneA monocyclic arene that is benzene substituted with one or more alkyl groups.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Bioassays (2)

Assay IDTitleYearJournalArticle
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (56)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's26 (46.43)29.6817
2010's30 (53.57)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 40.91

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index40.91 (24.57)
Research Supply Index4.32 (2.92)
Research Growth Index4.46 (4.65)
Search Engine Demand Index61.55 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (40.91)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials14 (23.33%)5.53%
Reviews20 (33.33%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other26 (43.33%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (23)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
An Open-label, Single Initial-dose, Multi-center Study to Assess the Transfer of Fospropofol and Its Active Metabolite, Propofol, to Breast Milk Following Administration of LUSEDRA to Lactating Women Undergoing a Needed Procedure [NCT01309984]Phase 110 participants (Actual)Interventional2010-11-30Completed
Efficacy and Safety of Fospropofol Disodium Versus Propofol for Deep Sedation in Critically Ill Patients [NCT05870514]Phase 260 participants (Anticipated)Interventional2023-06-01Recruiting
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 Inje [NCT01308541]Phase 120 participants (Actual)Interventional2011-01-31Completed
A DOSE RANGING STUDY TO EVALUATE THE EFFECTIVENESS OF FOSPROPOFOL (LUSEDRA®) FOR INDUCTION OF ANESTHESIA FOR OUTPATIENT UROLOGIC HYDRODILATION THERAPY [NCT01378754]0 participants (Actual)Interventional2011-06-30Withdrawn(stopped due to Loss of funding before enrollment.)
[NCT01289483]0 participants (Actual)Interventional2011-02-28Withdrawn(stopped due to sponsor has decided not to support this study.)
A Phase III, Randomized, Open-label Study to Assess the Safety and Efficacy of AQUAVAN® Injection Versus Midazolam HCl for Sedation in Patients Undergoing Flexible Bronchoscopy Procedures [NCT00209586]Phase 355 participants (Actual)Interventional2004-09-30Terminated(stopped due to Patient enrollment was stopped prior to completion of the study in order to re-evaluate the dosing regimen.)
A Prospective Randomized Study to Assess the Efficacy and Safety of Bolus-dose Lusedra (Fospropofol Disodium) 6.5 mg/kg or 10 mg/kg Versus a Placebo (With Midazolam Rescue) for Minimal-to-moderate Sedation in Patients Undergoing Procedural Sedation for Re [NCT01195103]Phase 413 participants (Actual)Interventional2011-02-28Terminated(stopped due to Funding terminated by funding source.)
A Phase III, Randomized, Open-label Study to Assess the Safety and Efficacy of AQUAVAN® Injection Versus Midazolam HCl for Sedation in Patients Undergoing Minor Surgical Procedures [NCT00209560]Phase 3168 participants (Actual)Interventional2004-10-31Terminated
A Phase 2, Two Part Study of AQUAVAN® Injection in the Presence of Pre-Medication in Patients Undergoing Elective Colonoscopy [NCT00209534]Phase 2200 participants Interventional2003-01-31Completed
A Phase III, Randomized, Open-Label Study to Assess the Safety and Efficacy of AQUAVAN Injection Versus Midazolam HCl for Sedation in Patients Undergoing Colonoscopy Procedures [NCT00209573]Phase 3270 participants Interventional2004-09-30Completed
A Phase III, Randomized, Open-Label Study to Assess the Safety and Efficacy of AQUAVAN® Injection Versus Midazolam HCl for Sedation in Patients Undergoing Percutaneous Coronary (PC) Procedures [NCT00209547]Phase 3110 participants Interventional2004-02-29Completed
Efficacy and Safety of Fospropofol Disodium Versus Propofol for Sedation in Mechanically Ventilated ICU Patients [NCT05491278]Phase 260 participants (Actual)Interventional2022-08-10Completed
A Randomized, Open-Label, Single-Bolus, 2-Period, Multi-Dose Level, 3 Cohort Crossover Design, Pharmacokinetic/Pharmacodynamic Study of Lusedra (Fospropofol Disodium) Injection Compared With Propofol Injectable Emulsion [NCT01260142]Phase 436 participants (Actual)Interventional2010-11-30Completed
A Randomized, Double-Blind, Dose-Response Study to Assess the Efficacy and Safety of AQUAVAN® Injection for Procedural Sedation in Patients Undergoing Colonoscopy [NCT00125424]Phase 2/Phase 3125 participants Interventional2005-07-31Completed
Phase 2, Randomized Study of AQUAVAN® Injection In Elective Coronary Artery Surgery With Comparison to DISOPRIVAN® Injectable Emulsion [NCT00209521]Phase 216 participants (Actual)Interventional2002-06-30Completed
A Phase II, Randomized, Open-Label Study to Examine the Safety and Efficacy of GPI 15715 for Sedation of Patients Requiring Intubation and Mechanical Ventilation in the Intensive Care Unit Setting [NCT00125398]Phase 260 participants Interventional2005-07-31Completed
A Phase 1,Open, Dose-escalation Study to Assess the Efficacy and Safety of Fospropofol Disodium Injection in Healthy Volunteers [NCT01271569]Phase 180 participants (Actual)Interventional2010-03-31Completed
A Phase 3 Open-Label, Single Arm Study to Assess the Safety of AQUAVAN® (Fospropofol Disodium) Injection for Minimal-to-Moderate Sedation in Patients Undergoing Minor Surgical Procedures [NCT00327392]Phase 2/Phase 3123 participants (Actual)Interventional2006-05-31Completed
A Phase 3, Randomized, Double-Blind, Dose-Controlled Study to Assess the Efficacy and Safety of AQUAVAN® (Fospropofol Disodium) Injection for Minimal to Moderate Sedation in Patients Undergoing Colonoscopy [NCT00261599]Phase 3300 participants Interventional2006-03-31Completed
A Phase 3, Randomized, Double-Blind, Dose-Controlled Study To Assess The Efficacy And Safety Of AQUAVAN® (Fospropofol Disodium) Injection For Minimal-To-Moderate Sedation In Patients Undergoing Flexible Bronchoscopy [NCT00306722]Phase 3250 participants Interventional2006-04-30Completed
A Double-blind, Randomized, Multicenter, Dose-ranging Study to Evaluate the Safety and Efficacy of LUSEDRA (Fospropofol Disodium) as an Intravenous Sedative for Diagnostic or Therapeutic Colonoscopy in Adult Special Populations [NCT01127438]Phase 4153 participants (Actual)Interventional2010-04-30Completed
A Phase II, Randomized, Open-Label Study to Assess the Safety and Efficacy of AQUAVAN® Injection Versus Midazolam HCl for Sedation in Elderly Patients Undergoing Colonoscopy Procedures [NCT00209599]Phase 2100 participants Interventional2005-02-28Terminated
Preventing Propofol Injection Pain: Prospective Randomized Trial Comparing Propofol Versus Fospropofol [NCT01401049]Phase 4116 participants (Actual)Interventional2010-08-31Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00209560 (2) [back to overview]Time to Fully Alert From the End of the Procedure
NCT00209560 (2) [back to overview]Successful Sedation of Subjects, Defined for a Subject as Having 3 Consecutive Scores ≤ 4 on the Modified Observer's Assessment of Alertness/Sedation Scale and Completing the Procedure w/o Alternative Sedative Medications/w/o Manual/Mechanical Ventilation
NCT00327392 (1) [back to overview]Incidence of Airway Assistance in Patients Undergoing Minor Surgical Procedures
NCT01127438 (3) [back to overview]Number of Participants With Modified Sedation Success
NCT01127438 (3) [back to overview]Number of Participants With Sedation Success
NCT01127438 (3) [back to overview]Number of Participants With Treatment Success
NCT01195103 (1) [back to overview]Percentage of Participants Achieving Sedation Within 4 Minutes
NCT01260142 (9) [back to overview]Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Fospropofol (AUC(0-inf))
NCT01260142 (9) [back to overview]Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Propofol
NCT01260142 (9) [back to overview]Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC(0-t)) of Fospropofol
NCT01260142 (9) [back to overview]Area Under the Plasma Concentration-Time Curve From Time 0 to Time t of Propofol
NCT01260142 (9) [back to overview]Maximal Sedative Effect Using the Bispectral Index (BIS) Score
NCT01260142 (9) [back to overview]Maximal Sedative Effect Using the Modified Observer's Assessment of Alertness/Sedation Scale
NCT01260142 (9) [back to overview]Maximum Drug Plasma Concentration (Cmax) of Fospropofol
NCT01260142 (9) [back to overview]Maximum Drug Plasma Concentration of Propofol
NCT01260142 (9) [back to overview]Relative Bioavailability of Fospropofol and Propofol

Time to Fully Alert From the End of the Procedure

Time to Fully Alert, defined as the time to the first of 3 consecutive Modified OAA/S scores of 5 from the end of the surgical procedure, was summarized. (NCT00209560)
Timeframe: At 2-minute intervals from the end of the procedure until the subject met the criteria for Fully Alert status

Interventionminutes (Mean)
Fospropofol Disodium8.4
Midazolam4.1

[back to top]

Successful Sedation of Subjects, Defined for a Subject as Having 3 Consecutive Scores ≤ 4 on the Modified Observer's Assessment of Alertness/Sedation Scale and Completing the Procedure w/o Alternative Sedative Medications/w/o Manual/Mechanical Ventilation

"The Modified OAA/S (MOAA/S) scale is based on a validated, 6-point rating scale. Scores are not combined.~Score 5 (alert) -- responds readily to name spoken in normal tone Score 4 -- Lethargic response to name spoken in normal tone Score 3 -- Responds only after name is called loudly and/or repeatedly Score 2 -- Responds only after mild prodding or shaking Score 1 -- Responds only after painful trapezius squeeze Score 0 -- Does not respond to painful trapezius squeeze" (NCT00209560)
Timeframe: Sedation success was assessed at 2 minute intervals until the end of the procedure

,
Interventionparticipants (Number)
pPI Population Sedation SuccessmITT Population Sedation Success
Fospropofol Disodium94.294.2
Midazolam78.678.6

[back to top]

Incidence of Airway Assistance in Patients Undergoing Minor Surgical Procedures

(NCT00327392)
Timeframe: 2 hours

Interventionparticpants (Number)
Verbal StimulationLoud Tone of VoiceFace MaskChin LiftOral AirwayIncreased Oxgen Flow
Fospropofol Disodium111112

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Number of Participants With Modified Sedation Success

Modified sedation success was defined as a subject who was a sedation success and did not have a MOAA/S score <2 any time after administration of sedative medication. Sedation success was defined as subjects who had 3 consecutive MOAA/S scores at or less than 4 after administration of sedative medication, completed the procedure, did not require the use of alternative sedative medication, and did not require manual/mechanical ventilation. The MOAA/S score was used to clinically rate the level of sedation using a score of 0 to 5 based on the level of responsiveness. (NCT01127438)
Timeframe: Day 1

InterventionParticipants (Number)
Subgroup 1, Lower Dose16
Subgroup 1, Approved Dose20
Subgroup 2, Lower Dose18
Subgroup 2, Approved Dose18
Subgroup 3, Lower Dose17
Subgroup 3, Approved Dose20

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Number of Participants With Sedation Success

Sedation success was defined as subjects who met the following 4 criteria: had 3 consecutive Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores at or less than 4 after administration of sedative medication, completed the procedure, did not require the use of alternative sedative medication, and did not require manual/mechanical ventilation. The MOAA/S score was used to clinically rate the level of sedation using a score of 0 to 5 based on the subject's level of responsiveness. A high score on the MOAA/S scale indicated a lower level of sedation. (NCT01127438)
Timeframe: Day 1

InterventionParticipants (Number)
Subgroup 1, Lower Dose18
Subgroup 1, Approved Dose24
Subgroup 2, Lower Dose18
Subgroup 2, Approved Dose21
Subgroup 3, Lower Dose19
Subgroup 3, Approved Dose24

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Number of Participants With Treatment Success

Treatment success was defined as subjects who met the following 3 criteria: completed the procedure, did not require the use of alternative sedative medication, and did not require manual/mechanical ventilation. (NCT01127438)
Timeframe: Day 1

InterventionParticipants (Number)
Subgroup 1, Lower Dose18
Subgroup 1, Approved Dose24
Subgroup 2, Lower Dose18
Subgroup 2, Approved Dose21
Subgroup 3, Lower Dose19
Subgroup 3, Approved Dose24

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Percentage of Participants Achieving Sedation Within 4 Minutes

"Percentage of patients achieving a Modified Observer's Assessment of Alertness/Sedation Scale score less than or equal to 4, and the block procedure initiated, within 4 minutes of the administration of the first bolus of study drug. The Modified Observer's Assessment of Alertness/Sedation Scale ranges from 0 (does not respond to deep stimulus) to 6 (agitated). The score of 4 equals lethargic response to name spoken in normal tone." (NCT01195103)
Timeframe: approximately 4 minutes after administration of first bolus of study drug

Interventionpercentage of participants (Number)
10 mg/kg Lusedra100
6.5 mg/kg Lusedra50
Placebo + Midazolam40

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Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Fospropofol (AUC(0-inf))

AUC(0-inf) is a measure of drug concentration equal to the area under the plasma concentration-time profile from time 0 to infinity. An arterial line (A-line) and venous line (V-line) were placed prior to dosing during each treatment period and used to collect blood samples for plasma concentration measurements at specific time points. Plasma arterial and venous concentrations of fospropofol were quantified by high-performance liquid chromatography with mass spectrometric detection (LC-MS/MS). The AUC(0-inf) was calculated from the sum of AUC from time 0 to time t (AUC(0-t)) and the residual area calculated as Ct/λz, where Ct was the observed concentration at last quantifiable concentration and λz was the terminal elimination rate constant. The plasma concentrations from the venous sampling were descriptively compared head-to-head with the arterial sampling. (NCT01260142)
Timeframe: Days 1, and 7-14 (Arterial Sample: Pre-dose, and 0.5, 1, 1.5, 2, 4, 8, 16, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose. Venous Sample: Pre-dose, and 1, 4, and 30 minutes post-dose).

Interventionug.h/L (Mean)
Fospropofol 6.5 mg/kg16522
Fospropofol 10 mg/kg25052
Fospropofol 15 mg/kg36629

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Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity of Propofol

An A-line and V-line were placed prior to dosing during each treatment period and used to collect blood samples for plasma concentration measurements at specific time points. Plasma arterial and venous concentrations of propofol were quantified by high-performance liquid chromatography with mass spectrometric detection (LC-MS/MS). The AUC(0-inf) was calculated from the sum of AUC(0-t) and the residual area calculated as Ct/λz, where Ct was the observed concentration at last quantifiable concentration and λz was the terminal elimination rate constant. The plasma concentrations from the venous sampling were descriptively compared head-to-head with the arterial sampling. In addition, the arterial plasma concentrations of fospropofol, propofol liberated from fospropofol, and propofol delivered from propofol injectable emulsion were used to refine the population PK model developed previously. (NCT01260142)
Timeframe: Days 1, and 7-14 (Arterial Sample: Pre-dose, and 0.5, 1, 1.5, 2, 4, 8, 16, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose. Venous Sample: Pre-dose, and 1, 4, and 30 minutes post-dose).

Interventionug.h/L (Mean)
Fospropofol 6.5 mg/kg1541
Propofol 0.65 mg/kg467
Fospropofol 10 mg/kg2368
Propofol 1.0 mg/kg661
Fospropofol 15 mg/kg3807
Propofol 1.5 mg/kg893

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Area Under the Plasma Concentration-Time Curve From Time 0 to Time t (AUC(0-t)) of Fospropofol

Arterial and venous blood samples were collected and analyzed for fospropofol concentrations as described previously. AUC(0-t) was calculated using the log-linear trapezoidal rule (linear trapezoidal rule up to maximum observed plasma concentration (Cmax), log trapezoidal rule following Cmax) from time of dosing to the last quantifiable concentration. The plasma concentrations from the venous sampling were descriptively compared head-to-head with the arterial sampling. (NCT01260142)
Timeframe: Days 1, and 7-14 (Arterial Sample: Pre-dose, and 0.5, 1, 1.5, 2, 4, 8, 16, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose. Venous Sample: Pre-dose, and 1, 4, and 30 minutes post-dose).

Interventionug.h/L (Mean)
Fospropofol 6.5 mg/kg16046
Fospropofol 10 mg/kg24473
Fospropofol 15 mg/kg36330

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Area Under the Plasma Concentration-Time Curve From Time 0 to Time t of Propofol

Arterial and venous blood samples were collected and analyzed for propofol concentrations as described previously. AUC(0-t) was calculated using the log-linear trapezoidal rule (linear trapezoidal rule up to Cmax, log trapezoidal rule following Cmax) from time of dosing to the last quantifiable concentration. The plasma concentrations from the venous sampling were descriptively compared head-to-head with the arterial sampling. In addition, the arterial plasma concentrations of fospropofol, propofol liberated from fospropofol, and propofol delivered from propofol injectable emulsion were used to refine the population PK model developed previously. (NCT01260142)
Timeframe: Days 1, and 7-14 (Arterial Sample: Pre-dose, and 0.5, 1, 1.5, 2, 4, 8, 16, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose. Venous Sample: Pre-dose, and 1, 4, and 30 minutes post-dose).

Interventionug.h/L (Mean)
Fospropofol 6.5 mg/kg1343
Propofol 0.65 mg/kg385
Fospropofol 10 mg/kg2009
Propofol 1.0 mg/kg578
Fospropofol 15 mg/kg3019
Propofol 1.5 mg/kg801

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Maximal Sedative Effect Using the Bispectral Index (BIS) Score

Pharmacodynamic (PD) effects were obtained from continuous BIS score recordings obtained throughout the study and from clinical assessment of sedation using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The BIS measurements continued until the participant was fully recovered in the opinion of the investigator or until the PD effect measure returned to baseline. The BIS score varied between 100 (associated with being fully awake) and 0 (associated with a flat line on the electroencephalogram (EEG)). The BIS Index was described by the maximal effect (Emax) model. (NCT01260142)
Timeframe: Days 1, and 7-14 (BIS measurements were to continue until the subject was fully recovered in the opinion of the investigator or until the PD effect measures returned to baseline measures)

InterventionScores on a scale (Mean)
Fospropofol 6.5 mg/kg70.2
Propofol 0.65 mg/kg81.5
Fospropofol 10 mg/kg55.4
Propofol 1.0 mg/kg65.8
Fospropofol 15 mg/kg38.6
Propofol 1.5 mg/kg49

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Maximal Sedative Effect Using the Modified Observer's Assessment of Alertness/Sedation Scale

PD effects were determined from continuous BIS score recordings and from clinical assessment of sedation using the MOAA/S scale. The MOAA/S scale was used to rate the level of alertness/sedation from a score of 0 (does not respond to painful stimulus) to 5 (alert) in the category of responsiveness, with 5 being the MOAA/S value for a fully awake adult. Time to sedation was defined as the time from the first dose of study medication to the first two consecutive MOAA/S scores less than or equal to 4. Fully awake status was reached at the first of 3 consecutive MOAA/S scores of 5 measured every 2 minutes after study drug administration. The MOAA/S scale was described by the Emax model. (NCT01260142)
Timeframe: Days 1, and 7-14 (2 minutes prior to study drug administration and every 2 minutes thereafter for 20 minutes or until the subject reached Fully Alert status, whichever was later).

InterventionScores on a scale (Mean)
Fospropofol 6.5 mg/kg4.1
Propofol 0.65 mg/kg4.7
Fospropofol 10 mg/kg2.8
Propofol 1.0 mg/kg3.9
Fospropofol 15 mg/kg0.3
Propofol 1.5 mg/kg1.7

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Maximum Drug Plasma Concentration (Cmax) of Fospropofol

Arterial and venous blood samples were collected and analyzed for fospropofol concentrations as described previously. Cmax was the highest plasma drug concentration observed over the entire sampling period, and was obtained directly from the experimental plasma concentration time data without interpolation. The plasma concentrations from the venous sampling were descriptively compared head-to-head with the arterial sampling. (NCT01260142)
Timeframe: Days 1, and 7-14 (Arterial Sample: Pre-dose, and 0.5, 1, 1.5, 2, 4, 8, 16, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose. Venous Sample: Pre-dose, and 1, 4, and 30 minutes post-dose).

Interventionug/mL (Mean)
Fospropofol 6.5 mg/kg95.6
Fospropofol 10 mg/kg146.3
Fospropofol 15 mg/kg207.3

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Maximum Drug Plasma Concentration of Propofol

Arterial and venous blood samples were collected and analyzed for propofol concentrations as described previously. Cmax was the highest plasma drug concentration observed over the entire sampling period, and was obtained directly from the experimental plasma concentration time data without interpolation. The plasma concentrations from the venous sampling were descriptively compared head-to-head with the arterial sampling. (NCT01260142)
Timeframe: Days 1, and 7-14 (Arterial Sample: Pre-dose, and 0.5, 1, 1.5, 2, 4, 8, 16, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose. Venous Sample: Pre-dose, and 1, 4, and 30 minutes post-dose).

Interventionug/mL (Mean)
Fospropofol 6.5 mg/kg1.5
Propofol 0.65 mg/kg8
Fospropofol 10 mg/kg2.1
Propofol 1.0 mg/kg8.6
Fospropofol 15 mg/kg3.1
Propofol 1.5 mg/kg9.5

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Relative Bioavailability of Fospropofol and Propofol

The PK parameters for propofol from propofol injectable emulsion were used as the reference formulation. Because propofol is a metabolite of fospropofol, all calculations were conducted after correcting for the different molecular weights of these formulations. Molecular weights of 332.24 (288.24 for free base) and 178.27 were used for fospropofol disodium and propofol injectable emulsion, respectively. The propofol parameters were adjusted as appropriate as discussed above and natural log transformed prior to comparison. Relative bioavailability of propofol from fospropofol disodium (E2083) to propofol from propofol injectable emulsion is calculated as (AUC(FP) x Total Dose of Propofol/AUC(P) x Total Dose of E2083) x Molecular fraction, where AUC(FP) is AUC(0-t) or AUC(0-inf) of propofol from E2083, AUC(P) is AUC(0-t) or AUC(0-inf) of propofol from propofol injectable emulsion and molecular fraction is molecular weight of propofol (178.27)/E2083 (332.24). (NCT01260142)
Timeframe: Days 1, and 7-14 (Arterial Sample: Pre-dose, and 0.5, 1, 1.5, 2, 4, 8, 16, 30, 45, 60, 120, 180, 240, 300, and 360 minutes post-dose. Venous Sample: Pre-dose, and 1, 4, and 30 minutes post-dose).

,,
Interventionng x hr/mL (Mean)
AUC(0-t)AUC(0-inf)
Cohort 1 (Fospropofol 6.5 : Propofol 0.65)0.6840.694
Cohort 2 (Fospropofol 10.0 : Propofol 1.0)0.6610.68
Cohort 3 (Fospropofol 15.0 : Propofol 1.5)0.7130.836

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