Study to Assess Safety & Efficacy of Sitagliptin as Initial Oral Therapy for Treatment of Type 2 Diabetes Mellitus in Pediatric Participants. (MK-0431-083)
Condition: Diabetes Mellitus; Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin; Metformin; Placebo to sitagliptin; Placebo to metformin; Glycemic Rescue 1; Glycemic Rescue 2
Intervention description: Sitagliptin 100 mg tablet administered orally once daily; Metformin 500 mg tablets administered orally starting at 500 mg/day and uptitrated by 500 mg every week to a final dose of 1000 mg twice daily; Matching placebo to sitagliptin 100 mg tablet administered orally once daily; Matching placebo to metformin 500 mg tablets, 2 tablets administered orally twice daily; Participants in the sitagliptin arm who require glycemic rescue will receive metformin during Weeks 0-20 and Weeks 20-54. Participants in the placebo arm who require glycemic rescue will receive metformin during Weeks 0-20. Participants in the placebo arm who have switched to metformin during Weeks 20-54 and require glycemic rescue will receive sitagliptin.; Participants who require glycemic rescue after Glycemic Rescue 1 will receive open-label insulin. Participants on background insulin therapy will have the dose of their background insulin up-titrated.
Intervention MeSH terms: Metformin; Sitagliptin Phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 200.0
Sex: All
Minimum age: 10 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to assess the safety of the addition of sitagliptin, and its
      effect on hemoglobin A1c (A1C) in pediatric participants 10-17 years of age with type 2
      diabetes mellitus (T2DM) with inadequate glycemic control. The primary hypothesis for this
      study is that sitagliptin reduces A1C more than placebo after 20 weeks of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 Diabetes Mellitus (T2DM)

          -  Has not received treatment with an antihyperglycemic agent (AHA) for ≥12 weeks prior
             to the Screening Visit/Visit 1, or is on a stable dose of insulin (without any other
             AHA) for at least 12 weeks prior to the Screening Visit/Visit 1. At screening,
             participants on insulin doses that are not stable can have their insulin doses
             adjusted and be eligible to participate after their dose remains stable for ≥12 weeks,
             if they meet all other eligibility criteria. In India, only participants on stable
             doses of insulin will be eligible.

          -  An A1C of ≥6.5% and ≤10.0% (For participants on insulin: an A1C ≥7.0% and ≤10.0%).

        Exclusion Criteria:

          -  History of type 1 diabetes mellitus, autoimmune diabetes mellitus or has a positive
             antibody screen for anti-GAD (Glutamic Acid Decarboxylase) or (Islet cell autoantigen)
             ICA-512.

          -  Known monogenic diabetes, secondary diabetes, or a genetic syndrome or disorder known
             to affect glucose tolerance other than diabetes.

          -  Symptomatic hyperglycemia and/or moderate to large ketonuria and/or positive test for
             ketonemia requiring immediate initiation of antihyperglycemic therapy.

          -  Previously taken a DPP-4 (Dipeptidyl peptidase-4) inhibitor (such as sitagliptin,
             vildagliptin, alogliptin, or saxagliptin) or GLP-1 (Glucagon-like peptide-1) receptor
             agonist (such as exenatide or liraglutide).

          -  Hypersensitivity or contraindication (according to the product circular in the country
             of the investigational site) to metformin.

          -  Chronic treatment with a medication known to cause weight gain within 30 days of study
             start or weight loss or increased blood glucose within 8 weeks of study start or
             treated with an anti-psychotic within the past 12 weeks.

          -  On a weight loss program and not in the maintenance phase or have undergone bariatric
             surgery within 12 months prior to study start.

          -  On or likely to require treatment with ≥14 consecutive days or repeated courses of
             pharmacologic doses of corticosteroids.

          -  Undergone a surgical procedure within the prior 4 weeks or has major surgery planned
             during the study.

          -  History of congenital heart disease or cardiovascular disease other than hypertension.

          -  Medical history of active liver disease (other than non-alcoholic hepatic steatosis),
             including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic
             gallbladder disease.

          -  Active nephropathy (i.e., nephrotic syndrome or glomerulonephritis).

          -  Chronic myopathy, mitochondrial disorder, or a progressive neurological or
             neuromuscular disorder (e.g., polymyositis, or multiple sclerosis).

          -  Human immunodeficiency virus (HIV) as assessed by medical history.

          -  Clinically significant hematological disorder (such as aplastic anemia,
             thrombocytopenia, myeloproliferative or myelodysplastic syndrome).

          -  Under treatment for hyperthyroidism.

          -  Exhibits abnormal growth patterns or is being treated with growth hormone.

          -  History of malignancy or clinically important hematologic disorder.

          -  History of idiopathic acute pancreatitis or chronic pancreatitis.

          -  Known history of recreational or illicit drug use, or of alcohol abuse or dependence
             (within the past year).

          -  Donated blood products or has had phlebotomy of >10% of estimated total blood volume
             within 8 weeks of signing informed consent, or intends to donate blood products or
             receive blood products within the projected duration of the study.

          -  Pregnant, has a positive urine pregnancy test at Screening Visit/Visit 1, is expecting
             to conceive within the projected duration of the study, or is breast-feeding.

          -  Exclusionary laboratory values.