Dose-ranging study of BTI320 in type 2 diabetic patients

Abstract

Background/objectives: Current practice is to treat diabetics with oral hypoglycemics, insulin, or a combination of both; these systemic interventions are not without risk. The reduction in glucose excursion is a new therapeutic paradigm with non-systemic interventions which has been suggested to delay diabetic-associated complications. BTI320, derived from galactomannan, is a non-systemic drug to attenuate postprandial glucose excursion by blocking carbohydrate hydrolyzing enzymes within the gastrointestinal tract. Earlier studies of BTI320 have shown decreased glucose excursions with relatively few adverse effects. Subjects/methods: This double-blind, placebo-controlled, 3-period crossover, outpatient study evaluated two different doses of BTI320, 4 g and 8 g three times daily before meals, for 7 days in 23 adults with Type 2 diabetes (mean age 54 years, BMI 31.4 kg/m2). The primary endpoint of the response of postprandial glucose excursion was measured by the area under the curve from 0 to 4 hours (PPG-AUC0-4) following a high carbohydrate meal on the final day of dosing in each crossover arm. Results: The mean (± SD) PPG-AUC0-4 after 7 days of dosing placebo, 4 g, and 8 g BTI320 were 179.09 ± 157.271, 146.61 ± 98.604, and 179.09 ± 157.27 mmol/L*min, respectively, in the intent-to-treat population, demonstrating appreciable effects of 4 g BTI-320 compared with placebo. Similar trends were found in the PPG peak glucose levels and time to peak glucose concentrations. Consistent with other studies, the mean glucose serum concentrations at 2 hours following 4 g BTI320 (7.57 ± 1.519 mmol/L) were markedly lower than those following placebo and 8 g BTI320 (7.63 ± 1.826 and 7.68 ± 1.711 mg/dL, respectively). Conclusion: Data from this proof of concept study comparing two doses (4 and 8 g) of BTI320 demonstrated evidence of 4 g BTI320 in reducing glucose excursions compared with the 8 g BTI320 and placebo arms per subject. Whereas these data support other published studies of BTI320 limiting the magnitude of glucose excursion, variables such as rate of glucose absorption, age of the patient, and amount of carbohydrates in each meal, amongst others, require an expanded population in a Phase 3 trial to confirm these findings. *Correspondence to: David R Luke, Senior Medical Consultant, Clinical Development, DRL Pharmaceutical Consulting, LLC, 43 Chriswood Trace, Ledyard, CT 06339 USA, Tel: (860) 608-5296, E-mail: DLuke4@Comcast.net