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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01204775
First received: September 16, 2010
Last updated: January 19, 2017
Last verified: January 2017
  Purpose
The purpose of this study is to evaluate the efficacy, safety, tolerability, of Saxagliptin in pediatric patients with type 2 diabetes.

Condition Intervention Phase
Type 2 Diabetes
Drug: Saxagliptin
Drug: Placebo (Saxagliptin)
Drug: Metformin IR
Drug: Placebo (Metformin)
Drug: Metformin (Active Rescue)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • The change from baseline in HbA1c at Week 16 [ Time Frame: 16 weeks ]

Secondary Outcome Measures:
  • AUC change from baseline in 2-hour PPG levels at Week 16, as determined from samples obtained during Mixed Meal Tolerance Test (MMTT). [ Time Frame: 16 weeks (or last measurement prior if no Week 16 assessment is available) ]
    Area under the curve (AUC), Postprandial Glucose (PPG)

  • The change from baseline in Fasting Plasma Glucose (FPG) at week 16 [ Time Frame: 16 weeks (or last measurement prior if no Week 16 assessment is available) ]
  • The percent of subjects who achieved Glycosylated hemoglobin (HbA1c) < 7% at week 16 [ Time Frame: 16 weeks (or last measurement prior if no Week 16 assessment is available) ]

Enrollment: 26
Study Start Date: June 2011
Study Completion Date: April 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • BMS-477118
  • Onglyza
Drug: Metformin (Active Rescue)
Tablets, Oral, 500 mg, Titrated as needed, 2-52 weeks
Placebo Comparator: Placebo
Placebo matching saxagliptin tablet
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
Drug: Metformin (Active Rescue)
Tablets, Oral, 500 mg, Titrated as needed, 2-52 weeks

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01204775

Locations
United States, California
Research Site
Los Angeles, California, United States
Research Site
San Diego, California, United States
United States, Florida
Research Site
Hollywood, Florida, United States
Research Site
Tallahassee, Florida, United States
Research Site
Tampa, Florida, United States
United States, Michigan
Research Site
Dearborn, Michigan, United States
United States, New York
Research Site
Buffalo, New York, United States
United States, Tennessee
Research Site
Memphis, Tennessee, United States
United States, Virginia
Research Site
Richmond, Virginia, United States
Russian Federation
Research Site
Moscow, Russian Federation
Research Site
Novosibirsk, Russian Federation
Research Site
Saint Petersburg, Russian Federation
South Africa
Research Site
Cape Town, South Africa
Research Site
Pretoria, South Africa
Taiwan
Research Site
Taichung, Taiwan
Research Site
Taipei, Taiwan
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01204775     History of Changes
Other Study ID Numbers: CV181-058  2010-020360-38 
Study First Received: September 16, 2010
Last Updated: January 19, 2017

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 17, 2017