Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Saxagliptin as Monotherapy in Pediatric Patients With Type 2 Diabetes
Condition: Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Saxagliptin; Placebo (Saxagliptin); Metformin IR; Placebo (Metformin); Metformin (Active Rescue)
Intervention description: Tablets, Oral, 2.5 mg or 5.0 mg (according to body weight category), Once Daily, 1-52 weeks; Tablets, Oral, Once daily, 1-16 weeks; Tablets, Oral, 500 mg, Once Daily, 17-52 weeks; Tablets, Oral, Once daily, 1-16 weeks; Tablets, Oral, 500 mg, Titrated as needed, 2-52 weeks
Intervention MeSH terms: Metformin; Saxagliptin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 26.0
Sex: All
Minimum age: 10 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy, safety, tolerability, of Saxagliptin
      in pediatric patients with type 2 diabetes.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients eligible if 10 years of age, up to 17 years and 32 weeks of
             age at the time of randomization, diagnosed as having type 2 diabetes prior to study
             enrollment.

          -  HbA1c ≥7.0% and ≤10.5%

          -  Body weight ≥ 30 kg.

          -  BMI > 85th percentile

        Age and Reproductive Status a) Women of childbearing potential (WOCBP) and men must be
        using an acceptable method of contraception to avoid pregnancy throughout the study and for
        up to 4 weeks after the last dose of investigational product in such a manner that the risk
        of pregnancy is minimized. The decision for appropriate methods to prevent pregnancy should
        be determined by discussions between the investigator and the study subject.

        b) WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or
        equivalent units of HCG) within 72 hours prior to the start of investigational product. c)
        Women must not be breastfeeding. d) Sexually active fertile men must use effective birth
        control if their partners are WOCBP.

        Exclusion Criteria:

          1. Target Disease Exceptions

             a) Current use of the following medications for the treatment of diabetes, or use
             within the specified timeframe prior to screening for the study: i) Six months:
             insulin. ii) Four months: thiazolidinediones. iii) Two months: any other antidiabetic
             treatment iv) Any previous use of DPP4-inhibitor and/or incretin mimetics b) Current
             use of prescription or non-prescription weight loss drugs and their use within 3
             months of screening.

          2. Medical History and Concurrent Diseases

             a) Significant co-morbidity that, in the opinion of the investigators would preclude
             participation in the study (eg, current treatment for cancer). b) Previous diagnosis
             of monogenic etiology of type 2 diabetes such as MODY (maturity onset of diabetes in
             youth) or secondary diabetes (steroid use, Cushing's disease, acromegaly). c)
             Significant cardiovascular history. d) History of hemoglobinopathies (sickle cell
             anemia or thalassemias, sideroblastic anemia). e) History of unstable or rapidly
             progressive renal disease. f) History of alcohol or drug abuse. g) Psychiatric or
             cognitive disorder that will, in the opinion of investigators, limit the patient's
             ability to comply with the study medications and monitoring. h) Administration of any
             other study drug or participation in a clinical research trial within 30 days of
             planned enrollment to this study (or a longer period if dictated by local regulatory
             authorities). i) Any condition, which in the investigator's opinion may render the
             subject unable to complete the study or may pose significant risk to the subject. j)
             Immunocompromised individuals such as subjects that have undergone organ
             transplantation or subjects diagnosed with human immunodeficiency virus. k) Subjects
             on a commercial weight loss program with ongoing weight loss, or on an intensive
             exercise program.

          3. Physical and Laboratory Test Findings a) Fasting plasma glucose (FPG) > 255 mg/dL
             (14.2 mmol/L) at screening will exclude the patient. b) Diabetic ketoacidosis (DKA)
             within 6 months of study entr1) Target Disease Exceptions a) Current use of the
             following medications : i) Six months: insulin. ii) Four months: thiazolidinediones.
             iii) Two months: any other antidiabetic treatment iv) Any previous use of
             DPP4-inhibitor and/or incretin mimetics b) Current use of prescription or
             non-prescription weight loss drugs and their use within 3 months of screening.

        2) Medical History and Concurrent Diseases

        a) Significant co-morbidity that, in the opinion of the investigators would preclude
        participation in the study (eg, current treatment for cancer). b) Previous diagnosis of
        monogenic etiology of type 2 diabetes such as MODY (maturity onset of diabetes in youth) or
        secondary diabetes (steroid use, Cushing's disease, acromegaly). c) Significant
        cardiovascular history. d) History of hemoglobinopathies (sickle cell anemia or
        thalassemias, sideroblastic anemia). e) History of unstable or rapidly progressive renal
        disease. f) History of alcohol or drug abuse. g) Psychiatric or cognitive disorder that
        will, in the opinion of investigators, limit the patient's ability to comply with the study
        medications and monitoring. h) Administration of any other study drug or participation in a
        clinical research trial within 30 days of planned enrollment to this study (or a longer
        period if dictated by local regulatory authorities). i) Any condition, which in the
        investigator's opinion may render the subject unable to complete the study or may pose
        significant risk to the subject. j) Immunocompromised individuals such as subjects that
        have undergone organ transplantation or subjects diagnosed with human immunodeficiency
        virus. k) Subjects on a commercial weight loss program with ongoing weight loss, or on an
        intensive exercise program. 3) Physical and Laboratory Test Findings

          1. Fasting plasma glucose (FPG) > 255 mg/dL (14.2 mmol/L) at screening

          2. Diabetic ketoacidosis (DKA) within 6 months of study entry (DKA can occur as a
             presenting sign of type 2 diabetes in youth).

          3. Abnormal renal function, which is defined as an abnormal creatinine clearance rate as
             determined by the Schwartz Formula

        Exclusion from study participation will apply to calculated glomerular filtration rate < 80
        mL/min/1.73m2 (1.33 mL/s). d) Presence of one or more of the following: antibodies to
        glutamic acid decarboxylase (GAD), islet cell autoantibody (ICA), protein tyrosine
        phosphatase-like protein antibodies (IA-2). e) Active liver disease and/or significant
        abnormal liver function defined as Aspartate aminotransferase (AST) and/or alanine
        aminotransferase (ALT) > 2 times upper limits of normal, and/or serum total bilirubin > 2.0
        mg/dL. f) History of positive serologic evidence of current infectious liver disease
        including anti-HAV (IgM), HbsAg, or anti-HCV. Patients who may have isolated positive anti
        HBs may be included. g) Anemia of any etiology defined as hemoglobin ≤ 10.7 g/dL (107 g/L)
        for females and ≤ 11.3 g/dL (113 g/L) for males. h) An abnormal TSH value at screening will
        be further evaluated by free T4. Subjects with an abnormal T4 will be excluded. i)
        Creatinine kinase (CK) ≥ 3 X ULN. j) Clinically significant (CS) abnormalities in any
        pre-randomization laboratory analyses or ECG that, in the investigator's opinion, would
        preclude randomization. 4) Allergies and Adverse Drug Reaction

          1. Subjects who have contraindications to therapy as outlined in the Saxagliptin
             Investigator Brochure or local metformin package insert.

          2. Subjects with known contraindications to DPP-IV therapy. 5) Prohibited Therapies
             and/or Medications

        a) Steroid use exclusions: i) Excluded: use of oral or parenteral corticosteroids within 3
        months ii) Allowed: inhaled corticosteroids for asthma, and topical corticosteroids if
        limited to minor surface area. b) Use of any other antihyperglycemic medication (other than
        metformin or insulin as applicable for glycemic rescue) after entry into the placebo
        lead-in period. c) Prior treatment with saxagliptin. d) Subjects taking prohibited
        medication as listed in Section 3.4. Subjects who stop prohibited medication prior to study
        participation must undergo an appropriate wash out period before visit 1. e) Diabetes
        treatment or use of weight loss medications f) Current treatment with potent CYP3A4/5
        inhibitors (in countries where dose adjustment would be required by the saxagliptin label).
        6) Sex and Reproductive Status

        a) Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical
        trials, or breastfeeding. 7) Other Exclusion Criteria

          1. Prisoners or subjects who are involuntarily incarcerated.

          2. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (eg, infectious disease) illness.

          3. Employees of BMS, AstraZeneca (AZ), or their relatives.