A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination With Insulin) (MK-0431A-170/MK-0431A-289)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Sitagliptin plus metformin; Placebo to metformin; Metformin; Placebo to sitagliptin plus metformin; Sitagliptin plus metformin XR; Placebo to metformin XR; Insulin; Placebo to sitagliptin plus metformin XR; Metformin XR
Intervention description: Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1700 mg or 2000 mg of metformin. Dosage of metformin was based on each participant's daily metformin dose prior to enrollment.; Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin.; Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 1000 mg, 1700 mg or 2000 mg of metformin. Dosage was based on each participant's daily metformin dose prior to enrollment.; Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to sitagliptin plus metformin.; Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1500 mg or 2000 mg of metformin. Dosage of metformin XR was based on each participant's daily metformin dose prior to enrollment.; Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR.; Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue. During Weeks 20-54, for participants who were not on background insulin or rescued with insulin during Weeks 0-20 in the "Sitagliptin/Metformin" and "Metformin" arms (protocol MK-0431A-170), and during Weeks 0-54 for participants not on background insulin in the "Sitagliptin/Metformin XR" and "Metformin XR" arms (protocol MK-0431A-289), the type of insulin for glycemic rescue was specified to be insulin glargine.; Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to sitagliptin plus metformin XR.; Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 1000 mg, 1500 mg or 2000 mg of metformin XR. Dosage was based on each participant's daily metformin dose prior to enrollment.
Intervention MeSH terms: Metformin; Sitagliptin Phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants enrolled in protocol MK-0431A-170 were randomized between the arms "Sitagliptin/Metformin" and "Metformin." Participants enrolled in protocol MK-0431A-289 were randomized between the arms "Sitagliptin/Metformin XR" and "Metformin XR."
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Participants enrolled in protocol MK-0431A-170 were aware that they would receive either sitagliptin and metformin, or metformin. Participants in protocol MK-0431A-289 were aware that they would receive either sitagliptin and metformin XR, or metformin XR.
Enrollment: 223.0
Sex: All
Minimum age: 10 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the effect of the addition of sitagliptin
      (administered as MK-0431A or MK-0431A XR) relative to the addition of placebo on glycated
      hemoglobin (A1C), and the safety and tolerability of the addition of sitagliptin, in
      pediatric participants (ages 10-17 years) with type 2 diabetes mellitus with inadequate
      glycemic control on metformin therapy (alone or in combination with insulin). The primary
      hypothesis is that the addition of sitagliptin reduces glycated hemoglobin (A1C) more than
      the addition of placebo after 20 weeks of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  For MK-0431A-170 base study and MK-0431A-289:

               -  Has type 2 diabetes mellitus (T2DM)

               -  Is on metformin monotherapy (≥1500 mg/day) for ≥12 weeks with glycated hemoglobin
                  (A1C) ≥6.5% and ≤10.0% OR is on stable doses of metformin (≥1500 mg/day) and
                  insulin for ≥12 weeks with an A1C ≥7.0% and ≤10%. NOTE: Participants on a daily
                  dose of metformin greater than or equal to 1000 mg/day, but less than 1500 mg/day
                  may be eligible if there is documentation that higher doses are not tolerated.

               -  Participant and a family member or adult closely involved in the daily activities
                  will participate in the participant's treatment and study protocol (i.e.,
                  available for telephone calls, study visits and administration of study
                  medication as needed).

               -  Male, or female who is unlikely to conceive (non-sterilized, and is not sexually
                  active or agrees to abstain from heterosexual activity or agrees to use an
                  adequate method of contraception) during the study and for 14 days after the last
                  dose of study drug

          -  For MK-0431A-170 extension protocol:

               -  Has completed the P170 base study

               -  Participant and a family member or adult closely involved in the daily activities
                  will participate in the participant's treatment and study protocol (i.e.,
                  available for telephone calls, study visits and administration of study
                  medication as needed).

               -  Male, or female who is unlikely to conceive (non-sterilized, and is not sexually
                  active or agrees to abstain from heterosexual activity or agrees to use an
                  adequate method of contraception) during the study and for 14 days after the last
                  dose of study drug

        Exclusion Criteria:

          -  For MK-0431A-170 base study and MK-0431A-289:

               -  Has type 1 diabetes mellitus

               -  Has monogenic diabetes or secondary diabetes

               -  Has symptomatic hyperglycemia and/or moderate to large ketonuria and/or positive
                  test for ketonemia, requiring immediate initiation of another antihyperglycemic
                  agent

               -  Has previously taken a dipeptidyl peptidase IV (DPP-4) inhibitor (such as
                  sitagliptin, vildagliptin, alogliptin, saxagliptin, or linagliptin) or
                  glucagon-like peptide-1 (GLP-1) receptor agonist (such as exenatide or
                  liraglutide)

               -  Is on or likely to require treatment for ≥2 consecutive weeks or repeated courses
                  of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)

               -  Has undergone a surgical procedure within 4 weeks of study participation or has
                  planned major surgery during the study

               -  History of congenital heart disease or cardiovascular disease other than
                  hypertension

               -  History of active liver disease (other than non-alcoholic steatosis), including
                  chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic
                  gallbladder disease

               -  Active neuropathy (such as nephrotic syndrome or glomerulonephritis)

               -  Chronic myopathy, mitochondrial disorder or a progressive neurological or
                  neuromuscular disorder

               -  Human immunodeficiency virus (HIV)

               -  Hematological disorder (such as aplastic anemia, thrombocytopenia,
                  myeloproliferative or myelodysplastic syndromes)

               -  Is currently being treated for hyperthyroidism or is on thyroid hormone therapy
                  and has not been on a stable dose for at least 6 weeks

               -  History of malignancy for ≤5 years prior to study participation, except for
                  adequately treated basal cell or squamous cell skin cancer, or in situ cervical
                  cancer

               -  History of idiopathic acute pancreatitis or chronic pancreatitis

               -  History of recreational or illicit drug use, or of alcohol abuse or dependence
                  (within the past year)

               -  Has donated blood products or has had phlebotomy of >10% of estimated total blood
                  volume within 8 weeks of study participation, or intends to donate blood products
                  or receive blood products within the projected duration of the study

               -  Is pregnant or breast-feeding, or is expecting to conceive or donate eggs during
                  the study, including 14 days following the last dose of study drug

          -  For MK-0431A-170 extension protocol:

               -  Participant meets a study medication discontinuation criterion at the last visit
                  of the MK-0431A-170 base study (Week 20)

               -  Has taken the last dose of study medication for the MK-0431A-170 base study more
                  than 14 days prior to Extension Visit 1

               -  Has initiated another oral antihyperglycemic agent

               -  Participant does not agree to refrain from participating in any other
                  double-blind interventional study while participating in the P170 extension study