An Extension Protocol to Evaluate Dose Comparisons of Leucine-Metformin Combinations in Type 2 Diabetic Patients

This is a randomized, 8-week, extension of Study NS-0100-01, to evaluate the effect of various fixed-dose (FDC) combinations of leucine and metformin compared to standard metformin monotherapy on glycemic control.

Subjects meeting all inclusion criteria and no exclusion criteria for the extension study, including completion of the 4-week treatment period of Study NS-0100-01 [Day 28/Visit 7]), will be eligible to enroll into the extension. During participation in the extension, subjects will continue to receive their assigned treatment based upon the randomization that occurred on Day 1 (Visit 4) of Study NS-0100-0. The study will include a total of 3 visits: Visit 1E (Day 28/Visit 7 of Study NS-0100-01), Visit 2E (Day 56/Week 8), and Visit 3E (Day 84/Week 12). Key assessments at Visit 2E and Visit 3E include HbA1c, fasting plasma glucose, and plasma insulin. In addition, 3-hour standardized meal tests will be performed on Day 28 (as part of the Study Termination [Visit 7] procedures of Study NS-0100-01 prior to enrolling into the extension) and at Study Termination for the extension (Visit 3E [Day 84/Week 12]).

Inclusion criteria

• Has completed Study NS-0100-01, including all procedures required at Study Termination (Day 28/Visit 7) without major protocol deviations
• Is male, or female and, if female, meets all of the following criteria:

• Not breastfeeding
• Post-menopausal or negative pregnancy test result (human chorionic gonadotropin, beta subunit [β-hCG]) at Screening (Visit 1) (not required for hysterectomized females)
• If of childbearing potential (including perimenopausal women who have had a menstrual period within one year) and sexually active, must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, i.e., less than 1% per year, when used consistently and correctly, such as double barrier methods [male condom with spermicide, with or without cervical cap or diaphragm], implants, injectables, oral contraceptives [must have been using for at least the last 3 months], some intrauterine contraceptive devices, tubal ligation, or a vasectomized partner) during the entire duration of the study.
• Is able to read, understand, and sign the informed consent forms (ICF) and if applicable, an authorization to use and disclose protected health information form (consistent with health insurance portability and accountability act of 1996 [HIPAA] legislation), communicate with the investigator, and understand and comply with protocol requirements.

Exclusion criteria

Subjects who meet any of the following criteria will be excluded from the study.

• Is undesirable as a study participant as judged by the investigator (e.g., exhibited poor compliance during Study NS-0100-01)
• Is expected to require treatment, or if currently on a stable dose, changes to their regimen of the following medications:

• Lipid-lowering agents
• Anti-hypertensive medications
• Thyroid replacement therapy
• Non-steroidal anti-inflammatory agents
• Is expected to require or undergo treatment with any of the following medications:

• Antidiabetes medications (with the exception of study medication [i.e., metformin])
• Oral or parenteral steroids.