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

This study has been terminated.
(Release of Post Marketing Requirement for this study. Terminated November 2013.)
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01525225
First received: January 31, 2012
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Metformin immediate release (IR)
Drug: Saxagliptin
Drug: Metformin IR
Drug: Saxagliptin/Metformin XR FDC
Drug: Metformin XR
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death [ Time Frame: Day 1 up to Day 8, plus 30 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Marked Chemistry or Hematology Laboratory Abnormalities [ Time Frame: Day 1 to Day 8 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 4
Study Start Date: September 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC Drug: Metformin immediate release (IR)
Tablet, Oral, 1000 mg, twice daily, 1 day
Other Name: Glucophage® IR
Drug: Saxagliptin
Tablet, Oral, 5 mg, single-dose, 1 day
Drug: Metformin IR
Tablet, Oral, 1000 mg, twice daily, 5 days
Other Name: 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 Name: Glucophage® 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

  Eligibility

Ages Eligible for Study:   10 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01525225

Locations
United States, Arkansas
Osborne Research Center
Little Rock, Arkansas, United States, 72201
United States, California
Axis Clinical Trials
Los Angeles, California, United States, 90036
United States, Kentucky
Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States, 40202
United States, Missouri
The Children'S Mercy Hospital And Clinics
Kansas City, Missouri, United States, 64108
United States, Ohio
Promedica Toledo Children'S Hospital
Toledo, Ohio, United States, 43606
Promedica Toledo Childrens Hospital
Toledo, Ohio, United States, 43606
United States, Pennsylvania
Childrens Hospital Of Pittsburgh Of Upmc
Pittsburgh, Pennsylvania, United States, 15224
Sponsors and Collaborators
Bristol-Myers Squibb
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01525225     History of Changes
Other Study ID Numbers: CV181-153
Study First Received: January 31, 2012
Results First Received: August 11, 2014
Last Updated: August 11, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

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

ClinicalTrials.gov processed this record on October 20, 2014