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)
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: MK-8521; Liraglutide; Placebo
Intervention MeSH terms: Liraglutide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 87.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

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)