Health Condition 1: null- Type 2 Diabetes Mellitus
Conditions
Interventions
Intervention1: Double-blind Saxagliptin Tablet: 2.5 mg, or Saxagliptin Tablet, 5 mg, or Placebo for Saxagliptin.
Tablets will be provided at randomization. Glucophage 500 mg IR or Glucophage 500 mg XR
Sponsors
BristolMyers Squibb
Astra Zeneca
Eligibility
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Freely given informed consent must be obtained prior to clinical trial participation, including informed consent for any screening procedures conducted to establish subject eligibility for the trial. Minorâ??s parents or legally acceptable representatives must give fully informed written consent. Assent should be obtained according to local regulations and if child is mentally capable. 2) Target Population a) Male and female patients 10 years of age, up to 17 years and 30 weeks of age at the time of screening. b) Previously diagnosed as having type 2 diabetes for at least 2 months by WHO/ADA diagnostic criteria for glucose levels (FPG greater than 7.0 mmol/L [126 mg/dL] or plasma glucose levels 2-hours after 75-mg oral glucose load of greater than 11.1 mmol/L [200 mg/dL] or a casual plasma greater than 200 mg/dL with symptoms WHO 1999; WHO 2006; ADA 2010). c) HbA1c greater than or equal to 7.0% and less than or equal to 10.5% obtained at screening visit followed by randomization HbA1c greater than or equal to 6.5% and Less than or equal to 10.5% obtained during lead in. d) Body weight greater than or equal to 30 kg. e) BMI greater than 85th percentile. f) Stable dose of metformin (greater than or equal to 1000mg - less then or Equal to 2000mg) for a minimum of 2 months. 3) 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. See Section 3.3.3 for the definition of WOCBP. The decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject. b) Women 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
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 main study i) Six months: insulin (Exceptions: Short-term insulin therapy during hospitalization for causes other than diabetes should be discussed with the Medical Monitor). ii) Four months: thiazolidinediones. iii) Two months: any other antidiabetic treatment including, but not limited to, sulfonylureas, alpha glucosidase inhibitors, metiglinide, oral or injectable incretins or incretin mimetics. iv) Any previous use of DPP4-inhibitor and/or incretin mimetics • Exceptions: Patients who are taking metformin monotherapy for 2 months or longer may participate. 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), genetic disorders with strong associations with insulin resistance/diabetes and/or obesity such as Turnerâ??s Syndrome and Prader-Willi, or secondary diabetes (steroid use, Cushingâ??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 patientâ??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 Investigatorâ??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) greater than 255 mg per dL (14.2 mmol per L) at screening will exclude the patient from the study. 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 15as follows: estimated Glomerular Filtration Rate, eGFR (ml per min per 1.73m2) equal to 0.413 multiplied to (height (cms)per serum creatinine (mg perdl): If serum creatinine concentration is measured in SI units (umoles per L), divide this number by the conversion factor of 88.4 to get the SI units (mg per dl) before inserting into the Schwartz formula to calculate eGFR. Exclusion from study participation will apply to calculated glomerular filtration rate less than 80 mLper
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare after 16 weeks of oral double-blind treatment the mean change from baseline in HbA1c achieved with saxagliptin and placebo as add on therapy to metformin IR or metformin XR Timepoint: The primary objective is based on a 16 week treatment period. Statistical analysis of the outcome data will be available upon completion of the final Clinical Trial Report â?? currently targeted for May of 2015. | — |
Secondary
| Measure | Time frame |
|---|---|
| To compare after 16 weeks of oral double-blind treatment the effects of saxagliptin versus placebo as add on therapy to metformin IR or metformin XR on: 1. The AUC change from baseline in 2-hour PPG levels, as determined from samples obtained during Mixed Meal Tolerance Test (MMTT) 2. The change from baseline in FPG 3. The percent of subjects who achieved HbA1c less then 7%. Timepoint: The secondary objective is based on a 16 week treatment period. Statistical analysis of the outcome data will be available upon completion of the final Clinical Trial Report â?? currently targeted for May of 2015. | — |
Countries
Argentina, Australia, Belgium, Canada, India, Israel, Italy, Mexico, Russian Federation, South Africa, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactDr Sumit Arora
PAREXEL International
Outcome results
None listed