Phase 1 Study of the Pharmacology of BTI320 Before High-Glycemic Meals.

BTI320 is a proprietary fractionated mannan polysaccharide being studied for attenuation of postprandial glucose excursion. The apparent blood glucose-lowering effect of this compound is effective in lowering postprandial hyperinsulinemia, participating in the metabolic regulation of other lipid molecules; the consequence of this activity is yet to be validated with BTI320 with respect to the risk of cardiovascular disease. The primary objective of the study was to determine the postprandial glucose and insulin responses to 3 test meals containing rice alone or consumed with BTI320 (study A) or 3 test meals (SpriteTM ) alone or consumed with BTI320 (study B). Twenty overweight but otherwise healthy volunteers, 4 female and 6 male (mean age 29 years, BMI 27-28 kg/m2 ) in study A and 6 female and 4 male (mean age 32 years, BMI 25-32 kg/m2 ) in study B participated in the BTI320 evaluations. Standardized postprandial response methodology was utilized. In study A the addition of 6- and 12-g BTI320 tablets reduced postprandial glucose responses to white rice by 19% and 32% and reduced postprandial insulin responses by 16% and 24%, respectively (P ≤ .05). In study B 2.6 and 5.2 g BTI320 reduced the glycemic index by 10% and 14%, respectively, and led to 14% and 18% decreases in the insulinemic index of the soft drink (P ≤ .05). These 2 studies demonstrated that the consumption of BTI320 before carbohydrate food or sugary beverage significantly reduced postprandial glucose levels and insulin responses to that meal or beverage in a dose-dependent manner.

A proof-of-concept study to evaluate the efficacy and safety of BTI320 on post-prandial hyperglycaemia in Chinese subjects with pre-diabetes.

BACKGROUND: Galactomannan(s) are plant-derived fiber shown to reduce post-prandial blood glucose by delaying intestinal absorption of carbohydrates and slowing down gastric emptying. We examined glucose-lowering effects of BTI320, a propriety fractionated mannan(s) administered as a chewable tablet before meal in a proof-of-concept study in Chinese subjects with prediabetes. METHODS: Sixty Chinese adults aged 18-70 years with either impaired fasting glucose, impaired glucose tolerance, or glycated haemoglobin 5.7-6.4% (39-46 mmol/mol), were randomly assigned in 2:2:1 ratio to either BTI320 8 g (high dose), BTI320 4 g (low dose) or matching-placebo three times daily before meal for 16 weeks. The primary endpoint was change in fructosamine in subjects treated with BTI320 compared with placebo from baseline to week 4. Indices of glycaemic variability based on continuous glucose monitoring (CGM) and standard meal tolerance test were explored in secondary analyses. RESULTS: Of 60 subjects randomized, 3 subjects discontinued study treatment prematurely. In intention-to-treat analysis, no significant differences in change in serum fructosamine between low or high dose BTI320 and placebo were observed. Using random effect models, adjusted for variability by meals, treatment with low dose BTI320 was associated with reduction in 1-h (p < 0.01), 2-h (p = 0.01) and 3-h (p = 0.02) post-prandial incremental glucose area-under-curve and post-meal maximum glucose (p = 0.03) compared with placebo. Subjects receiving low dose BTI320 had greater body weight reduction than placebo group. CONCLUSIONS: BTI320 did not change fructosamine levels compared with placebo. BTI320 reduced glycaemic variability based on CGM indices. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov , reference number NCT02358668 (9 February 2015).

Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs.

We determined the dose-dependent effects of OC99, a novel, stabilized hemoglobin-based oxygen-carrier, on hemodynamics, systemic and pulmonary artery pressures, surrogates of tissue oxygen debt (arterial lactate 7.2 ± 0.1 mM/L and arterial base excess -17.9 ± 0.5 mM/L), and tissue oxygen tension (tPO2) in a dog model of controlled severe oxygen-debt from hemorrhagic shock. The dose/rate for OC99 was established from a pilot study conducted in six bled dogs. Subsequently twenty-four dogs were randomly assigned to one of four groups (n = 6 per group) and administered: 0.0, 0.065, 0.325, or 0.65 g/kg of OC99 combined with 10 mL/kg lactated Ringers solution administered in conjunction with 20 mL/kg Hextend IV over 60 minutes. The administration of 0.325 g/kg and 0.65 g/kg OC99 produced plasma hemoglobin concentrations of 0.63 ± 0.01 and 1.11 ± 0.02 g/dL, respectively, improved systemic hemodynamics, enhanced tPO2, and restored lactate and base excess values compared to 0.0 and 0.065 g/kg OC99. The administration of 0.65 g/kg OC99 significantly elevated pulmonary artery pressure. Plasma hemoglobin concentrations of OC99 ranging from 0.3 to 1.1 g/dL, in conjunction with colloid based fluid resuscitation, normalized clinical surrogates of tissue oxygen debt, improved tPO2, and avoided clinically relevant increases in pulmonary artery pressure.