Fospropofol Disodium Is Effective and Safe for Sedation during Colonoscopy

Abstract

Purpose: Fospropofol disodium (FP), a water-soluble prodrug of propofol, possesses a pharmacokinetic profile characterized by a smooth and predictable rise in propofol plasma concentrations that is unique from its active metabolite, propofol. This double-blind, multicenter, phase 3 study evaluated the safety & efficacy of FP 6.5 mg/kg & 2 mg/kg in patients undergoing colonoscopy. Methods: 314 patients ≥18 years (ASA P1 to P3) were randomized to FP 6.5 mg/kg, FP 2 mg/kg, or midazolam (MD) 0.02 mg/kg in a 3:2:1 allocation following pretreatment with fentanyl 50 mcg. Patients were permitted to receive up to 3 supplemental doses of study drug before being considered a treatment failure & receiving an alternative sedative. Sedation was assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S). The primary endpoint was sedation success, defined by 3 consecutive MOAA/S scores of ≤4 after administration of sedative, and completion of the procedure without use of an alternative sedative medication & without manual/mechanical ventilation. Other endpoints included measures of clinical benefit, recovery, memory retention, patient & physician satisfaction, and safety. Results: Sedation success (87% vs 26%; P < .001) was higher and the requirement for supplemental analgesic medication lower (55% vs 77%; P= .001) in the FP 6.5 mg/kg group than the FP 2 mg/kg group. Patients in the 6.5 mg/kg group were less likely to remember being awake during the procedure (51% vs 100%; P < .0001). The majority of patients in both groups reported willingness to use the sedative again (96% vs 91%). Patients in the FP 6.5 mg/kg group had higher memory retention (67%) than patients in the FP 2 mg/kg group (59%). Mean physician satisfaction scores were higher is the FP 6.5 mg/kg group (7.7) than in the FP 2 mg/kg group (4.5), P < .001. FP was well tolerated, with no serious treatment-related adverse events (TRAEs), deaths, or AE-related procedure discontinuations. The most common TRAEs in the FP 6.5 mg/kg and 2 mg/kg groups were paresthesias (68% vs 60%) and pruritus (16% vs 26%). Six patients experienced transient sedation-related AEs: FP 6.5 mg/kg (hypoxemia [resolved following repeated verbal stimulation, N = 1], hypotension [N = 2]); FP 2 mg/kg (hypotension [N = 2]); midazolam (hypotension). Conclusion: The FP 6.5 mg/kg dosing regimen is safe and effective for sedation during colonoscopy and is associated with a high level of sedation success, patient and physician satisfaction, and clear-headed recovery.