Multicenter Study to Evaluate the Effect of BTI320 on Glycemic Control in Type 2 Diabetes

The objective of the current study is to investigate the efficacy and safety of BTI320 compared to placebo in addition to metformin and/or sulfonylureas on glycemic control over 12 weeks in subjects with type 2 diabetes mellitus. This is a randomized, placebo-controlled, double-blind, multi-center study with two treatment arms. Study duration will be approximately 12 weeks. Participants will ingest 4 g BTI320 or matching placebo approximately 10 minutes before starting a meal, 3 times per day, at breakfast, lunch, and dinner. Participants will be instructed not to take the Investigational Medicinal Product with other drugs at the same time. Additional mealtime medication must be taken after consumption of the meal. A nutritionist, dietitian, or study personnel will provide instructions to subjects regarding dietary intake and the need to keep a detailed food record in an online calorie counter and have it entered into an electronic data capture during the study period. In general, subjects will be asked to follow normal meal plans recommended to patients with diabetes. Non-compliance will be defined as taking <80% or >120% of Investigational Medicinal Product during any outpatient evaluation period (visit to visit). Subjects who are non-compliant will be replaced to meet the goal of 60 evaluable subjects. Eight study visits will be scheduled after the Screening visit: Baseline (day 0), weeks 3, 6, and 12 (Visits 2, 4, 6, and 8 respectively) for safety and efficacy assessments and Visits 3, 5, 7 and 9 to remove the Continuous Glucose Monitoring System.

Inclusion criteria

• 18-75 years old.
• Established type 2 diabetes as assessed by:

• Fasting blood glucose (>126 mg/dL/7 mmol/L), or
• 2 hr oral glucose tolerance test (>200 mg/dL/11.1 mmol/L), or
• HbA1c is ≥7.0% within 3 months of enrollment and on a stable dose of metformin and/or sulfonylureas for at least 12 weeks.
• Body Mass Index (BMI) >23 kg/m2.
• Treated with metformin and/or sulfonylureas (monotherapy or combination therapy) stable and maximally tolerated for at least three months prior to study participation. Subjects should be on stable and maximally tolerated doses throughout the study unless sulfonylureas require adjustment to reduce the risk of hypoglycemia during the study.
• Subjects who are otherwise in generally satisfactory health.
• Likely to follow study requirements, in particular, to adhere to maintaining a suitable diet and keeping an online diary of their food intake and weight measured once weekly via EDC.
• Female subjects have negative urine pregnancy test at the Screening visit.
• Provides signed informed consent to participate in the study. Informed consent must be given by the subject prior to inclusion in the study, and before performing any study procedures, including the screening visit.

Exclusion criteria

• Have type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]).
• Treated with long-acting glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, alpha-glucosidase inhibitor, regular insulin, rapid-acting insulin analog, or sodium-glucose cotransport-2 inhibitors (SGLT-2). Treatment with any of these drugs should have been stopped at least 3 months before inclusion.
• Current or recent (within past 30 days) participation in another investigational drug or device study.
• Have participated in a previous study of BTI320.
• Have any uncontrolled cardiovascular risk factors (hypertension, hyperlipidemia), past clinical manifestation of coronary artery disease, blood dyscrasias, or significant cerebrovascular disease in the previous year. Any concomitant drug treatment for a condition not related to diabetes should be discussed and approved with the study Medical Monitor.
• Pregnant or breastfeeding, or plan to become pregnant within one year after randomization.
• Food allergy or severe food intolerance assessed by the Principal Investigator.
• History of allergy or intolerance to BTI320 (PAZ320 or SugarDown) or equivalent.
• Have known condition(s) influencing their glycemic levels (e.g. Cushing syndrome, pancreatic diseases, acromegaly).
• Have human immunodeficiency virus (HIV) infection, hepatitis, tuberculosis, or other serious infectious disease.
• History of alcohol addiction or drug abuse (illegal or controlled pharmaceutical substances) within past year prior to randomization.
• Have planned major surgery within 6 months after randomization.
• Have a terminal illness.
• Serum creatinine of >1.4 mg/dL (>124 μmol/L) in women or >1.5 mg/dL (>133 μmol/L) in men or subjects with end-stage renal disease (Estimated Glomerular Filtration Rate calculated by CKD-EPI [eGFR] <10 mL/min/1.73 m2).
• Have serum Alanine Aminotransferase (SGPT) >3 times upper limit of normal.
• History of cancer, other than non-melanoma skin cancer, that requires treatment during the previous five years prior to randomization.
• History of hemolytic anemia, repeated blood transfusions, or other conditions making HbA1c results unreliable as an indicator of chronic glucose level; hematocrit (Hct) <35% for men and <33% for women.
• History of solid organ transplant.
• Treatment with systemic glucocorticoids (except for short-term therapy [5 days or less]).
• Treatment with atypical anti-psychotics.
• In the opinion of the principal investigator, the subject is unlikely to follow the study protocol.
• Employment/lifestyle that requires nocturnal hours.