A Preliminary Study of the Efficacy and Safety of MK-8521 for Type 2 Diabetes (MK-8521-004)
Condition: Type II Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: MK-8521; Placebo; Liraglutide; Metformin
Intervention description: Dose strengths: 180 μg QD administered subcutaneously. A 2-step dose escalation regimen [60 μg, 120 μg] over the first 2 weeks is used to achieve the final dose up to 180 μg.); 300 μg QD administered subcutaneously (A 3-step dose escalation regimen [60 μg, 120 μg, 180 μg] over the first 3 weeks is used to achieve the final dose up to 300 μg.; Double dummy matching placebo for the MK-8521 and placebo arms: matching placebo for MK-8521 300 μg QD administered subcutaneously; matching placebo for MK-8521 180 μg QD administered subcutaneously. A dose escalation regimen consistent with that of the MK-8521 300 μg and 180 μg arms of the study; mock escalation will be performed over the first 2 to 3 weeks.; Dose strength: 1.8 mg QD administered subcutaneously. A 2-step dose escalation regimen (0.6 mg, 1.2 mg) over the first 2 weeks is used to achieve the final dose up to 1.8 mg.; Metformin immediate release (IR) or metformin extended release (XR) administered ≥1000 mg QD as background therapy
Intervention MeSH terms: Metformin; Liraglutide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 176.0
Sex: All
Minimum age: 21 Years
Maximum age: 65 Years
Healthy volunteers: No

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 <-10.5% OR Be on
             dual therapy with metformin (>-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