Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials.

Abstract

OBJECTIVE\nCiprofol is a new intravenous anesthetic agent similar to propofol that has the pharmacodynamic characteristics of a rapid rate of onset and recovery in pre-clinical experiments. The aims of the present clinical trials were to compare the efficacy and safety of ciprofol emulsion for sedation or general anesthesia during colonoscopy and to define optimal doses for a subsequent phase III clinical trial.\n\n\nMETHODS\nA phase IIa multi-center, open-label, non-randomized, positive control, dose-escalating study was performed to determine a recommended phase IIb dose (RP2D) of ciprofol to induce sedation or anesthesia in patients undergoing colonoscopy. Phase IIb was also a multi-center clinical trial, but the patients were randomized into 3 groups at a ratio of 1:1:1. It was a double-blinded, propofol controlled study that administered ciprofol 0.4 mg/kg (n\u202f=\u202f31) and 0.5 mg/kg (n\u202f=\u202f32) or propofol at 2.0 mg/kg (n\u202f=\u202f31), with the aim of establishing the optimal dose of ciprofol. The primary endpoint was the colonoscopy success rate. Secondary endpoints were the duration of colonoscope insertion, recovery time, number of top-up doses needed, and the total dose of ciprofol or propofol required to maintain adequate sedation or anesthesia. In addition, we evaluated the satisfaction of sedation/anesthesia from the endoscopists, anesthetists and patients points of view. Safety was assessed according to the incidence of AEs including serious AEs and drug related AEs and the assessment of vital signs, a 12-lead ECG and laboratory tests.\n\n\nRESULTS\nIn the phase IIa trial, the colonoscopy success rates in the 0.2 ∼ 0.5 mg/kg ciprofol and propofol 2.0 mg/kg groups were 100% and all doses were safe and well tolerated. Ciprofol doses of 0.4 mg/kg and 0.5 mg/kg are recommended for subsequent IIb phases. In the phase IIb trial, a 100% success rate was reconfirmed in all the dosage groups. The mean time of colonoscope insertion in the ciprofol 0.4 mg/kg, ciprofol 0.5 mg/kg and propofol 2.0 mg/kg groups were 1.9, 1.5 and 1.5 min, the mean recovery times from colonoscope withdrawal were 6.1, 5.1, and 4.3 min, and the times to discharge were 11.8, 11.2 and 10.6 min, respectively. The satisfaction ratings of anesthetists in the ciprofol 0.5 mg/kg group (9.5 ± 0.8) were higher than in the ciprofol 0.4 mg/kg (9.2 ± 1.0) and propofol 2.0 mg/kg (9.2 ± 0.9) groups. The incidence of sedation and anesthesia-related AEs was highest in the propofol 2.0 mg/kg group (25.8%), followed by the ciprofol 0.5 mg/kg group (21.9%), and was least in the ciprofol 0.4 mg/kg group (16.1%) (P\u202f=\u202f0.750).\n\n\nCONCLUSIONS\nCiprofol was safe and well tolerated at doses ranging from 0.1 mg/kg to 0.5 mg/kg. Ciprofol 0.4-0.5 mg/kg induced equivalent sedation/anesthesia and had a similar safety profile to propofol 2.0 mg/kg during colonoscopy without producing serious AEs.