STUDY OBJECTIVE: To evaluate the safety of intravenous (IV) fospropofol when used to provide minimal to moderate sedation in patients undergoing minor surgical procedures. DESIGN: Phase 3, open-label, single-arm study. SETTING: Multi-center. PATIENTS: 123 ASA physical status I, II, III, and IV patients, aged>or=18 years. INTERVENTIONS: Patients were pretreated with fentanyl 50 microg before receiving an initial dose of IV fospropofol 6.5 mg/kg. Patients could receive up to 5 supplemental doses of fospropofol 1.63 mg/kg to reach a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score<or=4 to allow the start of the procedure and to maintain adequate sedation levels during the procedure. MEASUREMENTS: 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. MAIN RESULTS: A mean of 2.4 supplemental doses of fospropofol was administered, and in 60% of patients, two or fewer supplemental doses of fospropofol were sufficient to initiate and complete the procedure. Alternative sedative medication was administered in 6 of 123 patients (4.9%). Mean (SD) MOAA/S score during the procedure was 3.8 (0.5). Sixty-one percent (61%) of patients had a MOAA/S score of 5 (fully alert) within two minutes after the end of the procedure. Few patients (7 of 123; 5.7%) had MOAA/S scores of 0 to 1 (deep sedation) during the procedure, and all 7 were either ASA physical status I (n=1) or II (n=6). The most common treatment-related adverse events (TRAEs) were self-limited: paresthesias (62.6%) and pruritus (27.6%). Five patients experienced sedation-related adverse events, including hypotension (n=4), bradycardia (concurrently with hypotension and managed with atropine; n=1), or hypoxemia (less than one min and managed with chin lift and verbal stimulation; n=1). Twenty patients with previous or existing hepatic disease (ranging from minimal to severe) and 5 patients with severe renal impairment had adverse events similar to the overall population. No deaths were reported, and no patient discontinued the study due to adverse events. CONCLUSION: An initial dose of IV fospropofol 6.5 mg/kg with supplemental doses was safe and well-tolerated as moderate sedation for use in minor surgical procedures. Copyright (c) 2010 Elsevier Inc. All rights reserved.
STUDY OBJECTIVE: To evaluate the safety of intravenous (IV) fospropofol when used to provide minimal to moderate sedation in patients undergoing minor surgical procedures. DESIGN: Phase 3, open-label, single-arm study. SETTING: Multi-center. PATIENTS: 123 ASA physical status I, II, III, and IV patients, aged>or=18 years. INTERVENTIONS:Patients were pretreated with fentanyl 50 microg before receiving an initial dose of IV fospropofol 6.5 mg/kg. Patients could receive up to 5 supplemental doses of fospropofol 1.63 mg/kg to reach a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score<or=4 to allow the start of the procedure and to maintain adequate sedation levels during the procedure. MEASUREMENTS: 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. MAIN RESULTS: A mean of 2.4 supplemental doses of fospropofol was administered, and in 60% of patients, two or fewer supplemental doses of fospropofol were sufficient to initiate and complete the procedure. Alternative sedative medication was administered in 6 of 123 patients (4.9%). Mean (SD) MOAA/S score during the procedure was 3.8 (0.5). Sixty-one percent (61%) of patients had a MOAA/S score of 5 (fully alert) within two minutes after the end of the procedure. Few patients (7 of 123; 5.7%) had MOAA/S scores of 0 to 1 (deep sedation) during the procedure, and all 7 were either ASA physical status I (n=1) or II (n=6). The most common treatment-related adverse events (TRAEs) were self-limited: paresthesias (62.6%) and pruritus (27.6%). Five patients experienced sedation-related adverse events, including hypotension (n=4), bradycardia (concurrently with hypotension and managed with atropine; n=1), or hypoxemia (less than one min and managed with chin lift and verbal stimulation; n=1). Twenty patients with previous or existing hepatic disease (ranging from minimal to severe) and 5 patients with severe renal impairment had adverse events similar to the overall population. No deaths were reported, and no patient discontinued the study due to adverse events. CONCLUSION: An initial dose of IV fospropofol 6.5 mg/kg with supplemental doses was safe and well-tolerated as moderate sedation for use in minor surgical procedures. Copyright (c) 2010 Elsevier Inc. All rights reserved.