Assessing the PK and Effect on Glucose and GI Hormone Concentrations of Metformin Delayed-Release in Subjects With T2DM

Inclusion criteria

• Is 19 to 70 (inclusive) years old at Visit 1 (Screening).
• Is diagnosed with Type 2 Diabetes Mellitus with

• HbA1c between 6.0 to 9.5% (inclusive) for subjects managing their diabetes with:

i. Diet and exercise alone, or ii. A stable regimen (minimum of 2 months at Visit 1) of metformin alone, or iii. A stable regimen (minimum of 2 months at Visit 1) of DPP-4 inhibitor alone, OR

• HbA1c between 6.0 to 8.5% (inclusive) for subjects managing their diabetes with a stable (minimum of 2 months at Visit 1) combination regimen of metformin and DPP-4 inhibitors.
• Has serum creatinine below the upper limit of normal at Visit 1 and an estimated creatinine clearance above 80 using the Crockroft and Gault equation (CrCl = [(140 - age) x body weight in kg] / (serum creatinine x 72) x (0.85 for females) [ref. 3].
• Has a body mass index (BMI) of 25.0 to 40.0 kg/m^2 (inclusive) at Screening.
• Is male, or is female and meets all of the following criteria:

• Not breastfeeding
• Negative pregnancy test result (human chorionic gonadotropin, beta subunit) at Visit 1 (Screening) (not applicable to hysterectomized 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
• Has a physical examination with no clinically significant abnormalities as judged by the investigator.
• Ability to understand and willingness to adhere to protocol requirements.
• If on chronic thyroid pharmacologic therapy, the dose must be stable for at least 3 months prior to Visit 1 (Screening), and must have thyroid-stimulating hormone (TSH) test result in normal range at Visit 1 (Screening).

Exclusion criteria

• Has a clinically significant medical condition that could potentially affect study participation and/or personal well-being, as judged by the investigator, including but not limited to the following conditions:

• Hepatic disease
• Renal disease
• Gastrointestinal disease
• Endocrine disorder except diabetes
• Cardiovascular disease
• Seizure disorder
• Organ transplantation
• Chronic infection
• Has any chronic disease requiring medication that has been adjusted in the past 90 days (subjects may take acute intermittent over-the-counter medications such as Tylenol, if needed).
• Has any drug treatment that affects gastric pH (prescription or over-the-counter), including any antacids or medications such as Rolaids or Pepcid within 2 days of Visit 1 (Screening).
• Has had major surgery of any kind within 6 months of Visit 1 (Screening).
• Has received a blood transfusion within 6 months of Visit 1 (Screening).
• Has a history of >5 kg weight change within 3 months of Visit 1 (Screening).
• Has clinical laboratory test (clinical chemistry, hematology, or urinalysis) abnormalities other than those expected in subjects with diabetes and judged by the investigator to be clinically significant at Visit 1 (Screening).
• Has physical, psychological, or historical finding that, in the investigator's opinion, would make the subject unsuitable for the study.
• 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.
• Has donated blood within 2 months of Visit 1 (Screening) or is planning to donate blood during the study.
• Has used insulin within 3 months of Visit 1 (Screening).
• Has received GLP-1 receptor agonists and/or thiazolidinedione treatment within 6 months of Visit 1 (Screening).
• Has known intolerance to metformin.
• Has received any investigational drug within 1 month (or five half-lives of the investigational drug, whichever is greater) of Visit 1 (Screening).
• Has known allergies or hypersensitivity to any component of study treatment.
• Is employed by Elcelyx Therapeutics, Inc (that is an employee, temporary contract worker, or designee of the company).
• Smokes more than 10 cigarettes per day, 2 cigars per day, or uses more than 1 can of smokeless tobacco per week.