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

Inclusion criteria

• Is at least 25 years old at Visit 1 (Screening).
• Is male, or is female and meets all of the following criteria:

• Not breastfeeding
• Negative pregnancy test result at Visit 1 (not applicable to post-menopausal or surgically sterile females)
• Surgically sterile, postmenopausal, or if of childbearing potential, must practice and be willing to continue to practice appropriate birth control during the entire duration of the study.
• Body mass index (BMI) 20.0 to 45.0 kg/m² (inclusive) at Visit 1 (Screening).
• Has a physical examination with no clinically significant abnormalities as judged by the investigator.
• Has T2DM and an HbA1c of 7.5% to 10.5%, inclusive, at Visit 1.
• Has an estimated glomerular filtration rate (eGFR) value of ≥60 mL/min/1.73 m² based on the Modification of Diet in Renal Disease (MDRD) equation.
• Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 3 months prior to Visit 1:

• Thiazolidinedione, sulfonylurea, dipeptidyl peptidase-4 inhibitors, and alpha-glucosidase inhibitors
• Hormone replacement therapy (female subjects) and testosterone (male subjects)
• Oral contraceptives (female subjects)
• Antihypertensive agents
• Lipid-lowering agents
• Thyroid replacement therapy
• Antidepressant agents
• Ability to understand and willingness to adhere to protocol requirements.

Exclusion criteria

• 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:

• Hepatic disease
• Gastrointestinal disease
• Endocrine disorder (T2DM is allowed)
• Cardiovascular disease
• Central nervous system diseases
• Psychiatric or neurological disorders
• Organ transplantation
• Chronic or acute infection
• Orthostatic hypotension, fainting spells or blackouts
• Allergy or hypersensitivity.
• A history of diabetic ketoacidosis or hyperosmolar non-ketotic hyperglycemia within the past year.
• Prior major surgery of any kind within 6 months of Visit 1.
• A history of >3% weight change within 3 months of Visit 1.
• 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.
• An alanine aminotransferase or aspartate aminotransferase result >2.5 × upper limit of normal (ULN) or a bilirubin result >1.5 × ULN.
• A physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study.
• Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following excluded medications:

• Metformin within 2 months of Visit 1 (Screening)
• Insulin within 2 weeks of Visit 1 (Screening) or for more than 1 week within 3 months of Visit 1 (Screening)
• Glucagon-like peptide-1 receptor agonists or sodium-glucose co-transporter 2 inhibitors within 3 months of Visit 1
• Drugs known to affect body weight, including prescription medications and over-the-counter anti obesity agents within 3 months of Visit 1.
• 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
• 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)
• Cationic drugs that are eliminated by renal tubular secretion within 1 week of Visit 1.
• Iodinated contrast dye within 1 week prior to Visit 1.
• 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.
• Met DR or double-blind matching placebo for Met DR at any time prior to Visit 1 (Screening)
• 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.
• 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.
• Has known immune system based allergies or hypersensitivity to any component of study treatment. A history of gastrointestinal intolerance to metformin is not exclusionary.
• Is employed by Elcelyx Therapeutics, Inc. (that is an employee, contract worker, or designee of the company).
• 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.