Open-label, Dose-escalation Study of L-glucose as a Bowel Preparation Before Colonoscopy

Abstract

Purpose: To evaluate the safety, tolerance, and efficacy of three dosing strategies of L-glucose, a non-nutritive enantiomer of D-glucose (Raymer, et al. 2003), as a bowel cleanser prior to colonoscopy. Methods: Men and nonpregnant women over the age of 50 scheduled to undergo routine outpatient colonoscopy were eligible. Exclusion criteria included liver disease, CHF, and creatinine > 1.5 mg/dL. Study enrollment was designed to proceed sequentially in 3 escalating split-dosing cohorts of 24 subjects each (12M, 12F), with the lowest dose enrolling first: 24 g X 24 g, 36 g X 36 g, 48 g X 48 g. Subjects were admitted to one of two Phase I certified study facilities. All subjects drank clear liquids during the entire day before exam. L-glucose was administered as two 8-oz (236 mL) doses, one at 6 pm the evening before colonoscopy and one between 3-4 hours before exam. Bowel cleansing was rated using a global and segmental scoring system. Laboratory parameters were tested at screening, immediately before dosing, 2 hours after the second dose, and on the day following exam. Side effects were recorded by study personnel. Interim analyses of safety and efficacy were used to determine whether to enroll in the highest dosing cohort; if a target success rate of 21/24 Excellent (E) + Good (G) preps was not achieved in the lowest dosing groups, enrollment in the 48 g X 48 g cohort would proceed. Results: 72 subjects (24 in each cohort; 36M, 36F) were enrolled and completed the protocol. The cohorts were similar in age, ethnicity, and BMI. Bowel preparation success (E + G) was achieved in 19/24 (24 g), 21/24 (36 g), and 23/24 (48 g) subjects [see Table]. A dose-response relationship was observed for mean number of bowel movements: 7.6 ± 2.6 (24 g), 10.6 ± 3.9 (36 g), and 11.5 ± 5.5 (48 g). Tolerance to the bowel preparation process was rated “Good” or “Very Good” in 91.7% (24 g), 75.0% (36 g), and 87.5% (48 g). Side effects were reported as mild or moderate in all groups. Vomiting occurred in 2/24 (8.73%) 24 g subjects and 0/48 36 g and 48 g subjects. Taste was rated “Very Pleasant” or “Somewhat Pleasant” in 20/24 (24 g), 19/24 (36 g), and 20/24 (48 g) subjects. No adverse trends were observed in vital signs, routine hematology, serum chemistry, urinalysis, or liver function tests following treatment in each cohort. 70/72 (97.2%) subjects reported a willingness to take the preparation for a future exam.Table: Bowel preparation effectivenessConclusion: In this open-label feasibility study, L-glucose produced superior bowel cleansing in a split-dose of 48 g X 48 g with excellent tolerance and no significant adverse effects. Disclosure: Dr Balaban - Consultant, Fleet Laboratories Dr Thompson - Consultant, Fleet Laboratories. This research was supported by an industry grant from Fleet Laboratories.