Study of Saxagliptin, 5-Hydroxy Saxagliptin, and Metformin Concentrations/Levels in Pediatric Subjects With T2DM

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics of Saxagliptin, 5-hydroxy Saxagliptin, and Metformin in pediatric subjects with Type 2 diabetes mellitus (T2DM) following oral administration of Saxagliptin and Metformin XR fixed dose combination tablet and co-administration of Saxagliptin and Glucophage® (Metformin) IR tablets

Detailed Description
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The primary purpose is to assess the pharmacokinetics of Saxagliptin, 5-hydroxy Saxagliptin, and Metformin in pediatric subjects aged 10 to 17 years with T2DM following oral administration of Saxagliptin and Metformin XR fixed dose combination tablet and co-administration of Saxagliptin and Glucophage® (Metformin) IR tablets

Official Title
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Evaluation of the Pharmacokinetics of Saxagliptin, 5-Hydroxy Saxagliptin, and Metformin in Children and Adolescents Aged 10 to 17 Years With Type 2 Diabetes Mellitus Following Oral Administration of Saxagliptin and Metformin XR Fixed Dose Combination Tablet and Co-Administration of Saxagliptin and Glucophage® (Metformin) IR Tablets

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Metformin immediate release (IR)
* Drug: Saxagliptin
* Drug: Metformin IR
* Drug: Saxagliptin/Metformin XR FDC
* Drug: Metformin XR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of T2DM Male and female subjects ages 10-17 Body weight ≥50 kg Glycosylated hemoglobin (HbA1c) 6.5 to 10% Exclusion Criteria: Fasting plasma glucose (FPG) > 240 mg/dL at screening Abnormal renal function Active liver disease and/or significant abnormal liver function

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC<br> | Drug: Metformin immediate release (IR)<br>* Tablet, Oral, 1000 mg, twice daily, 1 day<br>* Other names: Glucophage® IR;Drug: Saxagliptin<br>* Tablet, Oral, 5 mg, single-dose, 1 day<br>Drug: Metformin IR<br>* Tablet, Oral, 1000 mg, twice daily, 5 days<br>* Other names: Glucophage® IR;Drug: Saxagliptin/Metformin XR FDC<br>* Tablet, Oral, 2.5 mg Saxagliptin/1000 mg Metformin extended release (XR), Single-dose of 2 tablets. Fixed dose combination (FDC).<br>Drug: Metformin XR<br>* Tablet, Oral, 500 mg, Single-dose of 4 tablets<br>* Other names: Glucophage® XR;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. | Day 1 up to Day 8, plus 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Marked Chemistry or Hematology Laboratory Abnormalities | Lower limit of normal (LLN); upper limit of normal (ULN); treatment (RX); pre-treatment (Pre-Rx); units per liter (U/L); millimoles per liter (mmol/L). Alkaline phosphatase U/L:>1.25*Pre-RX if Pre-RX >ULN or >1.25*ULN if Pre-RX <=ULN; aspartate aminotransferase U/L: >1.25*Pre-RX if Pre-RX>ULN or 1.25*ULN if Pre-RX<=ULN;alanine aminotransferase U/L: >1.25*Pre-RX if Pre-RX>ULN or 1.25*ULN if Pre-RX<=ULN;blood urea nitrogen mmol/L: >1.1*ULN if Pre-RX <=ULN or >1.2*Pre-RX if Pre-RX >ULN; total bilirubin µmol/L: >1.1*ULN if Pre-RX <=ULN or >1.25*Pre-RX if Pre-RX >ULN; creatine phosphokinase U/L: >1.5*Pre-RX if Pre-RX>ULN or >1.5*ULN if Pre-RX <= ULN. Grams per liter (g/L); cells per liter (c/L). Hemoglobin (g/L): <0.85* pre-RX; hematocrit (%): <0.85*pre-RX;erythrocytes (*10^12 c/L): <0.85*pre-RX; platelet count (*10^9 c/L): <0.85*LLN if pre-RX>=LLN, or if Pre-Tx <LLN; leukocytes (*10^9 c/L): <0.85*LLN if pre-RX <LLN,or <0.9*LLN if LLN<=Pre-RX<=ULN. | Day 1 to Day 8 |