a preliminary study of the efficacy and safety of mk-8521 for type 2 diabetes (mk-8521-004)

Conditions: Type II Diabetes Mellitus

Summary: this is a multicenter randomized, double-blind, placebo- and active-controlled (liraglutide; victoza®), parallel-group, clinical trial of mk-8521 in participants with type 2 diabetes mellitus (t2dm) with inadequate glycemic control while on a stable dose of metformin (≥1000 mg/day). the trial will include a 1-week screening period; at least an 8-week antihyperglycemic agent (aha) washout period, if required; a 14-week blinded therapy period (which includes single-blind run-in and double-blind therapy); and a 14-day post-treatment visit, 2 weeks after the last dose of investigational product. the primary hypothesis of the trial is that mk-8521 provides greater reduction in hemoglobin a1c relative to placebo after 12 weeks of once-daily administration in participants with t2dm with inadequate glycemic control on metformin monotherapy.


Eligibility criteria:
inclusion criteria: * have t2dm in accordance with american diabetes association guidelines * be on metformin monotherapy (\>-1000 mg/day: metformin ir or metformin xr) for at least 12 weeks prior to study start with a hemoglobin a1c (a1c) \>-7.5 and \ -1000 mg/day: dose stable for at least 4 weeks prior to study start) with an a1c of \>-7.0% and \<-10.0% and a second aha and be willing to washout the second aha. allowable ahas are dipeptidyl peptidase 4 (dpp-4 inhibitors), alpha-glucosidase inhibitors, sulfonylureas, and glinides. * have a body mass index (bmi) ≥23 kg/m\^2 and ≤40 kg/m\^2 * is a female who is not of reproductive potential, or is a female of reproductive potential who agrees to avoid becoming pregnant: while receiving study drug and for 14 days after the last dose of study drug exclusion criteria: * have a history of type 1 diabetes or a history of diabetic ketoacidosis * has a history of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrinopathies, drug- or chemical-induced, and post-organ transplant) * has been treated with any gut-derived incretin hormone glucagon-like peptide 1 (glp-1) receptor agonist (e.g. byetta™, victoza™ or investigational agents) within the last 6 months or has had glp-1 receptor agonist discontinued due to gastrointestinal intolerance or lack of efficacy. note: treatment with a glp-1 receptor agonist that was discontinued \>6 months prior to study start is not an exclusion if the glp-1 receptor agonist was discontinued for reasons other than gastrointestinal intolerance or lack of efficacy. * has a history of clinically significant gastrointestinal disorder (including diabetic gastroparesis; irritable bowel disease; recurrent episodes of nausea, vomiting, diarrhea and abdominal pain) * has a history of clinically significant and active, immunological, respiratory, genitourinary or major neurological (including stroke, transient ischemic attack and chronic seizures) abnormalities or diseases * has a history of cardiovascular disease (including diabetic cardiomyopathy) or significant cardiac condition (including a history of myocardial infarction, stable or unstable angina, arterial revascularization, pathologic, symptomatic or sustained tachyarrhythmia \[e.g. atrial fibrillation, sustained supraventricular tachycardia, symptomatic non-sustained supraventricular tachycardia, ventricular tachycardia, ventricular fibrillation, wolf-parkinson-white syndrome, congenital long qt syndrome, etc.\]) or heart failure * has a family history of medullary carcinoma of the thyroid or multiple endocrine neoplasm type-2 syndrome * has active diabetic proliferative retinopathy or a history of maculopathy * has human immunodeficiency virus (hiv) * has a medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic hepatitis b or c (assessed by medical history), primary biliary cirrhosis, or active symptomatic gallbladder disease * is on a weight loss medication or has undergone bariatric surgery * has a history of acute or chronic pancreatitis of any etiology * had an event of severe hypoglycemia with neuroglycopenia in the past 12 months * has a positive urine pregnancy test * is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of investigational product * routinely consumes \>1 alcoholic drinks per day or \>7 alcoholic drinks per week or engages in binge drinking * routinely consumes ≥480mg /day caffeine in caffeinated beverages (1 cup of coffee contains approximately 120 mg of caffeine * is taking a beta blocker or medications with sympathomimetic activity (e.g. pseudoephedrine, phenylpropanolamine, etc.) * is currently a user of nicotine or nicotine containing products or does not agree to refrain from using nicotine during the trial, including 14 days following the last dose of investigational product * is currently a user of any illicit drugs (including any marijuana use) or has a history of drug (including alcohol) abuse within approximately 5 years * has other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or blinded investigational product administration