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

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

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

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Metformin immediate release (IR); Drug: Saxagliptin; Drug: Metformin IR; Drug: Saxagliptin/Metformin XR FDC; Drug: Metformin XR

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72201
      • Osborne Research Center
  • California
    • Los Angeles, California, United States, 90036
      • Axis Clinical Trials
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kosair Charities Pediatric Clinical Research Unit
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • The Children's Mercy Hospital and Clinics
  • Ohio
    • Toledo, Ohio, United States, 43606
      • ProMedica Toledo Children's Hospital
    • Toledo, Ohio, United States, 43606
      • Promedica Toledo Childrens Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Childrens Hospital Of Pittsburgh Of Upmc

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:

• 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

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC

Drug: Metformin immediate release (IR); Tablet, Oral, 1000 mg, twice daily, 1 day; Other Names: Glucophage® IR; Drug: Saxagliptin; Tablet, Oral, 5 mg, single-dose, 1 day; Drug: Metformin IR; Tablet, Oral, 1000 mg, twice daily, 5 days; Other Names: Glucophage® IR; Drug: Saxagliptin/Metformin XR FDC; Tablet, Oral, 2.5 mg Saxagliptin/1000 mg Metformin extended release (XR), Single-dose of 2 tablets. Fixed dose combination (FDC).; Drug: Metformin XR; Tablet, Oral, 500 mg, Single-dose of 4 tablets; Other Names: Glucophage® XR

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• BMS clinical trial educational resource

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: January 31, 2012
• First Submitted That Met QC Criteria: January 31, 2012
• First Posted (Estimate): February 2, 2012

Study Record Updates

• Last Update Posted (Estimate): June 22, 2015
• Last Update Submitted That Met QC Criteria: May 27, 2015
• Last Verified: May 1, 2015

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: CV181-153