Study of the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Participants With Type 2 Diabetes Mellitus (MK-8521-003)

A Phase Ib, Multicenter, Placebo and Active- Comparator-Controlled, Randomized, Double-Blind, Clinical Trial to Evaluate the Safety and Efficacy of MK-8521 Compared to Placebo and a Diabetes Drug in Subjects With Type 2 Diabetes Mellitus

This study will evaluate the safety, efficacy, and pharmacokinetics of MK-8521 given once daily compared to placebo and another diabetes drug in participants with Type 2 diabetes mellitus (T2DM).

This study was modified by a protocol amendment to a 2-part trial to further test the safety and tolerability of MK-8521 at higher doses and to compare MK-8521 pharmacokinetics between participants with T2DM and healthy participants. An additional cohort of T2DM participants and a cohort of non-diabetic obese participants has been added.

Inclusion Criteria:

• Male, or female of non-childbearing potential with Type 2 diabetes mellitus (Parts 1 and 2) or non-diabetic (Part 2)
• Body mass index (BMI) between: ≥27 and ≤40 kg/m^2
• A1C (average blood sugar for the past 2 to 3 months) value ≥7.0 and ≤11.0 % (Part 1) or ≥ 6.5 and ≤11.0 % (Part 2) at the time of screening (T2DM participants)
• A1C value <5.7 at the time of screening (non-diabetic subjects in Part 2 only)
• On a stable dose of metformin (≥1000 mg total daily dose) for at least 12 weeks at the time of screening (T2DM participants)

Exclusion Criteria:

• Mentally or legally incapacitated
• History of clinically significant psychiatric disorder of the last 5 years. Participants with situational depression may be enrolled in the trial at the discretion of the Investigator
• History of Type 1 diabetes mellitus or a history of ketoacidosis
• History of clinically significant gastrointestinal, hematological, hepatic, immunological, renal, respiratory, genitourinary or major neurological abnormalities or diseases
• History of cardiovascular disease or cardiac conduction disorder
• History of cancer (malignancy). Exceptions may include adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignancies which have been successfully treated ≥10 years prior to the pre-screening visit
• History of proliferative diabetic retinopathy or maculopathy
• Clinically significant diabetic autonomic neuropathy
• QTc interval ≥470 msec (for males) or ≥480 msec (for females)
• Clinical significant electrocardiogram (ECG) abnormality
• Positive for hepatitis B surface antigen, hepatitis C antibodies, or human immunodeficiency virus (HIV)
• On a weight loss program and is not weight-stable (weight stable is defined history of <5% change in body weight in the last 3 months
• On a weight loss medication or has undergone bariatric surgery
• Major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit
• Participated in another investigational trial within 4 weeks prior to the pretrial (screening) visit
• History of acute or chronic pancreatitis of any etiology
• Mean value for triplicate semi-recumbent systolic blood pressure >160 mm Hg and/or diastolic blood pressure >90 mm Hg (after at least a 10-minute seated rest) and blood pressure is considered unlikely to be below these limits by Day-1 (Randomization) with initiation or adjustment of antihypertensive medication
• Event of severe hypoglycemia with seizure or loss of consciousness in the past 12 months
• Treated with anti-hyperglycemic agents other than metformin within the last 12 weeks
• Previous exposure to any glucagon-like peptide-1 (GLP-1) receptor agonist (e.g. Byetta™, Victoza™ or investigational agents)