Study to Assess the Effects and Safety of ZGN-1061 in Overweight and Obese Participants With Type 2 Diabetes

Participants will be enrolled in 1 of 2 groups. Approximately 120 participants will receive 0.05, 0.3, or 0.9 mg of ZGN-1061 or placebo (Group 1). An additional 40 participants will receive 0.9 or 1.8 mg of ZGN-1061 or placebo (Group 2).

• ZGN-1061 (Drug): ZGN-1061 is a methionine aminopeptidase 2 inhibitor
• Placebo (Drug): Placebo has the same excipients and appearance as ZGN-1061

Primary outcomes

• Change in HbA1c [12 weeks]
• Safety and tolerability as assessed by incidence of adverse events [12 weeks]
• Safety and tolerability as assessed by change in medication use, vital signs, physical examination findings, mental well-being questionnaires, laboratory evaluations, and electrocardiogram results [12 weeks]

Secondary outcomes

• Change in body weight [12 weeks]
• Change in fasting plasma glucose [12 weeks]
• Change in insulin [12 weeks]
• Change in C-peptide [12 weeks]
• Change in proinsulin [12 weeks]
• Change in glucagon [12 weeks]
• Proportion of subjects achieving HbA1c <7% and ≤6.5% [12 weeks]
• Change in beta-cell function [12 weeks]
• Change in insulin sensitivity [12 weeks]
• Change in preprandial and postprandial glycemic parameters as assessed by a mixed meal tolerance test in a subset of subjects [12 weeks]
• Change in waist and hip circumference [12 weeks]
• Change in biomarkers relevant to obesity and/or type 2 diabetes [12 weeks]
• Change in patient reported outcomes measures [12 weeks]

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

Subjects must meet the following criteria to participate in this study:

* Be between the ages of 18 and 70 years, inclusive.
* Overweight or obese with a body mass index of at least 27 kg/m².
* Have type 2 diabetes with HbA1c between 7% and 11%.
* For subjects taking approved antidiabetes medications, the doses must be stable as determined by the study doctor.
* For subjects who have had weight-loss surgery (example: gastric banding), the procedure must have occurred at least 1 year ago, and be verified with documentation or by a health professional associated with the surgery.

Exclusion Criteria:

Subjects cannot participate in this research study if they meet any of the following:

* Have taken another study drug or study device within the past 6 months.
* Are taking certain prescribed medications including narcotics or opiates.
* Consistent recent use of insulin.
* Have had recent major surgery or prolonged bed rest, or planning or likely to undergo any surgery during the research study.
* Have a history of bleeding disorders or risk factors for excessive blood clotting.
* Have difficulty giving blood.
* Have a history of drug and/or alcohol abuse.

• Dennis Kim, MD, Study chair, Zafgen, Inc.