Dose-Ranging Study to Evaluate the Glycemic Effects, Safety, and Tolerability of Metformin Delayed Release in Subjects With T2DM

Exclusion Criteria

• •1. Has a clinically significant medical condition as judged by the investigator that could potentially affect study participation and/or personal well-being, including but not limited to the following conditions:
• •1. Hepatic disease
• •2. Gastrointestinal disease
• •3. Endocrine disorder (T2DM is allowed)
• •4. Cardiovascular disease
• •5. Central nervous system diseases
• •6. Psychiatric or neurological disorders
• •7. Organ transplantation
• •8. Chronic or acute infection
• •9. Orthostatic hypotension, fainting spells or blackouts
• •10. Allergy or hypersensitivity.
• •2. A history of diabetic ketoacidosis or hyperosmolar non-ketotic hyperglycemia within the past year.
• •3. Prior major surgery of any kind within 6 months of Visit 1.
• •4. A history of \>3% weight change within 3 months of Visit 1.
• •5. A clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormality, other than that related to T2DM, judged by the investigator to be clinically significant at Visit 1.
• •6. An alanine aminotransferase or aspartate aminotransferase result \>2.5 × upper limit of normal (ULN) or a bilirubin result \>1.5 × ULN.
• •7. A physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study.
• •8. Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following excluded medications:
• •1. Metformin within 2 months of Visit 1 (Screening)
• •2. Insulin within 2 weeks of Visit 1 (Screening) or for more than 1 week within 3 months of Visit 1 (Screening)
• •3. Glucagon-like peptide-1 receptor agonists or sodium-glucose co-transporter 2 inhibitors within 3 months of Visit 1
• •4. Drugs known to affect body weight, including prescription medications and over-the-counter anti obesity agents within 3 months of Visit 1.
• •5. Systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary steroids known to have a high rate of systemic absorption within 3 months of Visit 1
• •6. Planned use of any drug treatment that affects gastric pH (prescription or over-the-counter), such as H2-receptor antagonists and proton pump inhibitors, after Visit 2 (Week -2), or planned chronic use of any antacids (i.e., more than twice per week) after Visit 2 (Week -2)
• •7. Cationic drugs that are eliminated by renal tubular secretion within 1 week of Visit 1.
• •8. Iodinated contrast dye within 1 week prior to Visit 1.
• •9. Investigational drug within 2 months (or five half-lives of the investigational drug, whichever is greater) of the date of the first dose of randomized study medication.
• •10. Met DR or double-blind matching placebo for Met DR at any time prior to Visit 1 (Screening)
• •9. Currently abuses drugs or alcohol or has a history of abuse that in the investigator's opinion would cause the individual to be noncompliant with study procedures.
• •10. Had a blood transfusion or experienced significant blood loss (i.e., \>500 mL), including loss due to blood donation, within 2 months prior to Visit 1 (Screening), or is planning to donate blood during the study.
• •11. Has known immune system based allergies or hypersensitivity to any component of study treatment. A history of gastrointestinal intolerance to metformin is not exclusionary.
• •12. Is employed by Elcelyx Therapeutics, Inc. (that is an employee, contract worker, or designee of the company).
• •13. Has a fasting plasma glucose value \>270 mg/dL at Visit 1 (Screening), Visit 2 (Week -2), and an unscheduled visit to be completed within 1 week following Visit 2. The unscheduled visit is to be completed only for subjects with a fasting plasma glucose value \>270 mg/dL at Visit 1 and Visit 2.