Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Saxagliptin as Monotherapy in Pediatric Patients With Type 2 Diabetes

A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Saxagliptin (BMS-477118) as Monotherapy in Pediatric Patients With Type 2 Diabetes

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Saxagliptin; Drug: Metformin (Active Rescue); Drug: Placebo (Saxagliptin); Drug: Metformin IR; Drug: Placebo (Metformin)

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 3

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Research Site
  • Novosibirsk, Russian Federation
    • Research Site
  • Saint Petersburg, Russian Federation
    • Research Site
• South Africa
  • Cape Town, South Africa
    • Research Site
  • Pretoria, South Africa
    • Research Site
• Taiwan
  • Taichung, Taiwan
    • Research Site
  • Taipei, Taiwan
    • Research Site
• United States
  • California
    • Los Angeles, California, United States
      • Research Site
    • San Diego, California, United States
      • Research Site
  • Florida
    • Hollywood, Florida, United States
      • Research Site
    • Tallahassee, Florida, United States
      • Research Site
    • Tampa, Florida, United States
      • Research Site
  • Michigan
    • Dearborn, Michigan, United States
      • Research Site
  • New York
    • Buffalo, New York, United States
      • Research Site
  • Tennessee
    • Memphis, Tennessee, United States
      • Research Site
  • Virginia
    • Richmond, Virginia, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Saxagliptin; Saxagliptin Tablet, 2.5 mg, or Saxagliptin Tablet, 5 mg, (based on subject's weight)	Drug: Saxagliptin; Tablets, Oral, 2.5 mg or 5.0 mg (according to body weight category), Once Daily, 1-52 weeks; Other Names: Onglyza; BMS-477118; Drug: Metformin (Active Rescue); Tablets, Oral, 500 mg, Titrated as needed, 2-52 weeks
Placebo Comparator: Placebo; Placebo matching saxagliptin tablet	Drug: Metformin (Active Rescue); Tablets, Oral, 500 mg, Titrated as needed, 2-52 weeks; Drug: Placebo (Saxagliptin); Tablets, Oral, Once daily, 1-16 weeks; Drug: Metformin IR; Tablets, Oral, 500 mg, Once Daily, 17-52 weeks; Drug: Placebo (Metformin); Tablets, Oral, Once daily, 1-16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean Change in HbA1c From Baseline to Week 16	16 week short term treatment period

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: September 16, 2010
• First Submitted That Met QC Criteria: September 16, 2010
• First Posted (Estimate): September 17, 2010

Study Record Updates

• Last Update Posted (Actual): April 18, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Saxagliptin
• Other Study ID Numbers: CV181-058; 2010-020360-38 (EudraCT Number)