Study to evaluate the efficacy, safety, tolerability, and pharmacokinetics of saxagliptin as monotherapy in pediatric patients with type 2 diabetes

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
• a) Fasting plasma glucose (FPG) > 255 mg/dL (14.2 mmol/L) at screening
• b) Diabetic ketoacidosis (DKA) within 6 months of study entry (DKA can occur as a presenting sign of type 2 diabetes in youth).
• c) 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
• a) Subjects who have contraindications to therapy as outlined in the Saxagliptin
• Investigator Brochure or local metformin package insert.
• b) 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
• a) Prisoners or subjects who are involuntarily incarcerated.
• b) Subjects who are compulsorily detained for treatment of either a psychiatric or
• physical (eg, infectious disease) illness.
• c) Employees of BMS, AstraZeneca (AZ), or their relatives.