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)

Conditions: Diabetes Mellitus

Summary: 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.


Eligibility criteria:
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)