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PK Study of Dapagliflozin in Pediatric Subjects With T2DM

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01525238
First received: January 31, 2012
Last updated: September 29, 2016
Last verified: September 2016
  Purpose
The primary purpose of this study is to evaluate the pharmacokinetics (PK) of Dapagliflozin in pediatric subjects with type 2 diabetes mellitus (T2DM)

Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Dapagliflozin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: A Randomized, Multi-Center, Parallel Group, Single-Dose, Pharmacokinetics and Pharmacodynamics Study of Dapagliflozin in Children and Adolescents Aged 10 to 17 Years With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration (Cmax) was measured by plasma concentration of Dapagliflozin over time. The geometric means are reported in nanograms per milliliter (ng/mL).

  • Median Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Time of maximum observed plasma concentration (Tmax) for Dapagliflozin was derived from plasma concentrations versus time data. Medians were reported in hours (h).

  • Geometric Mean of Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Dapagliflozin [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time zero extrapolated to infinite time was derived from concentration versus time data. Geometric means are reported in nanogram hours per milliliter (ng*hr/mL).

  • Geometric Mean of Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Dapagliflozin [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of Dapagliflozin over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL).

  • Mean Plasma Half-life (T-HALF) of Dapagliflozin [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Plasma half-life (T-Half) for Dapagliflozin was derived from plasma concentrations versus time data. Means are reported in hours.

  • Geometric Mean of Apparent Clearance After Extravascular Administration (CL/F) of Dapagliflozin [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Apparent clearance after extravascular administration (CL/F) of Dapagliflozin was derived from plasma concentrations versus time data. Geometric means are reported in milliliters per minute (mL/min).

  • Geometric Mean of Apparent Volume of Distribution at Terminal Phase After Extravascular Administration (Vz/F) of Dapagliflozin [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Geometric mean of apparent volume of distribution at terminal phase after extravascular administration of Dapagliflozin was derived from plasma concentration versus time data. Geometric means are reported in Liters (L)


Secondary Outcome Measures:
  • Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin 3-O-Glucuronide [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration (Cmax) was measured by plasma concentration of Dapagliflozin 3-O-Glucuronide over time. The geometric means are reported in nanograms per milliliter (ng/mL).

  • Median Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin 3-O-Glucuronide [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Time of maximum observed plasma concentration (Tmax) for Dapagliflozin 3-O-Glucuronide was derived from plasma concentrations versus time data. Medians were reported in hours (h).

  • Geometric Mean of Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Dapagliflozin 3-O-Glucuronide [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time zero extrapolated to infinite time was derived from concentration versus time data. Geometric means are reported in nanogram hours per milliliter (ng*hr/mL).

  • Geometric Mean of Area Under the Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Dapagliflozin 3-O-Glucuronide [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Area under the concentration-time curve from time zero to time of the last quantifiable concentration (AUC(0-T)) was measured by plasma concentration of Dapagliflozin 3-O-Glucuronide over time. The geometric means are reported in nanogram hours per milliliter (ng*h/mL).

  • Mean Plasma Half-life (T-HALF) of Dapagliflozin 3-O-Glucuronide [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: No ]
    Plasma half-life (T-Half) for Dapagliflozin was derived from plasma concentration versus time data. Means are reported in hours.

  • Mean Fasting Plasma Glucose Concentrations at Pre-dose on Day 1 and on Day 2 After an 8-hr Fasting [ Time Frame: Day 1 (Pre-dose) to Day 2 ] [ Designated as safety issue: No ]
    Plasma glucose concentrations were evaluated in all treated subjects at Day 1 pre-dose and at Day 2 after fasting for 8 hours. Means are reported in milligrams per deciliter (mg/dL).

  • Mean Change in Fasting Plasma Glucose From Baseline Until Day 2 [ Time Frame: Day 1 (Pre-dose) to Day 2 ] [ Designated as safety issue: No ]
    Plasma glucose concentrations were evaluated in all treated subjects at Day 1 pre-dose and at Day 2 after fasting for 8 hours. Mean change from baseline to Day 2 is reported in milligrams per deciliter (mg/dL).

  • Mean Total Amount of Glucose Excreted in Urine Over 24 Hours [ Time Frame: Time of dose to 24 hours post-dose, Day 1 to Day 2 ] [ Designated as safety issue: No ]
    The total amount of glucose excreted in urine was measured for 24 hours following administration of Dapagliflozin. Means are reported in grams.

  • Number of Participants With Vital Sign Abnormalities, Electrocardiogram (ECG) Abnormalities, or Physical Examination Abnormalities Following Study Drug Administration. [ Time Frame: Day 1 to Day 3 ] [ Designated as safety issue: Yes ]
    Participants were followed from dosing on Day 1 until study discharge on Day 3. The number of participants with investigator-assessed clinically-important abnormalities in vital sign measurements, ECGs or physical examinations was reported.

  • Number of Participants With Marked Hematology Laboratory Abnormalities [ Time Frame: Day 1 (Pre-dose) to Day 3 ] [ Designated as safety issue: Yes ]

    LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose (Day -1). Lab values that met the following criteria were marked as abnormalities:

    Hemoglobin (grams per deciliter:g/dL): <0.85*Pre-Rx. Hematocrit (%): <0.85*Pre-Rx. Platelet Count (x10^9 cells per liter:c/L): <0.85*LLN or >1.5*ULN (if Pre-Rx<LLN, use <0.85*Pre-Rx).

    Leukocytes (x10^3 cells per microliter: c/uL): <0.9*LLN, >1.2*ULN (if Pre-Rx<LLN, use <0.85*Pre-Rx or >ULN, if Pre- Rx>ULN, use >1.15*Pre-Rx or <LLN). Neutrophils (Absolute) (x10^3 c/uL): <=1.5. Lymphocytes (Absolute) (x10^3 c/uL): <0.75 or >7.5. Monocytes (Absolute) (x10^3 c/uL): >2.000. Basophils (x10^3 c/uL): >0.4. Eosinophils (Absolute) (x10^3 c/uL): >0.75. Blasts (Absolute) (x10^9 c/L) > 0.


  • Number of Participants With Marked Serum Chemistry Abnormalities [ Time Frame: Day 1 (Pre-dose) to Day 3 ] [ Designated as safety issue: Yes ]

    LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose. Lab values that met the following criteria were marked as abnormalities:

    Alkaline Phosphatase (units per liter: U/L), Aspartate Aminotransferase (U/L), Alanine Aminotransferase (U/L):

    >1.25*ULN (if Pre-Rx>ULN, use >1.25*Pre-Rx). Bilirubin (milligrams per deciliter: mg/dL): >1.1*ULN (if Pre-Rx>ULN, use >1.25*Pre-Rx).

    Blood Urea Nitrogen (mg/dL): >1.1*ULN (if Pre-Rx>ULN, use >1.2*Pre-Rx). Creatinine (micromoles per Liter (umol/L)): >1.5*ULN if Pre-Rx missing or <= ULN, >1.33*Pre-Rx if PreRx > ULN. Sodium (mmol/L): >1.05*ULN, 1.05*Pre-Rx if Pre-Rx>ULN: <0.95*Pre-Rx, >ULN. If Pre-Rx>ULN: >1.05*Pre-Rx, <LLN). Potassium(mmol/L), Chloride (mmol/L), Calcium(mmol/L): <0.9*LLN, >1.1*ULN (if Pre-Rx<LLN: <0.9*Pre-Rx, >ULN. If Pre-Rx>ULN: >1.1*Pre-Rx, <LLN). Phosphorus (mg/dL): <0.85*LLN, >1.25*ULN (if Pre-Rx<LLN, <0.85*Pre-Rx, >ULN. if Pre-Rx>ULN: >1.25*Pre-Rx, <LLN).


  • Number of Participants With Marked Abnormalities in Other Chemistry Testing [ Time Frame: Day 1 (Pre-dose) to Day 3 ] [ Designated as safety issue: Yes ]

    LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose. Lab values that met the following criteria were marked as abnormalities:

    Glucose, fasting serum (mmol/L): <0.8*LLN, >1.3*ULN (if Pre-Rx<LLN: <0.8*Pre-Rx, >ULN. If Pre-Rx>ULN: >2.0*Pre-Rx, <LLN).

    Protein (grams per deciliter: g/L): <0.9*LLN, >1.1*ULN (if Pre-Rx<LLN: <0.9*Pre-Rx, >ULN. If Pre-Rx>ULN:

    >1.1*Pre-Rx, <LLN). Albumin (g/L): <0.9*LLN (if Pre-Rx<LLN: <0.9*Pre-Rx). Uric Acid (mmol/L): >1.2*ULN (if Pre-Rx>ULN: >1.25*Pre-Rx).

    Lactate Dehydrogenase (U/L): >1.25*ULN (if Pre-Rx>ULN: >1.5*Pre-Rx)


  • Number of Participants With Marked Urinalysis Abnormalities [ Time Frame: Day 1 (Pre-dose) to Day 3 ] [ Designated as safety issue: Yes ]

    LLN=Lower Limit of Normal, ULN=Upper Limit of Normal, Pre-Rx=Value before first dose. Lab values that met the following criteria were marked as abnormalities:

    Blood, urine (Qualitative): >=2 (If Pre-Rx >= 1, >=2*Pre-Rx). Glucose, urine (Qualitative): >=1, (If Pre-Rx >=1, >=2*Pre-Rx). Protein, urine (Qualitative): >=2 (If Pre-Rx >=1, >=2*Pre-Rx). Red Blood Cells (RBC), urine (RBC per High Power Field (hpf)): >=2 (If Pre-Rx>=2, >=4).

    White Blood Cells (WBC), urine (hpf): >=2 (If Pre-Rx>=2, >=4).



Enrollment: 53
Study Start Date: July 2012
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dapagliflozin 2.5 mg Drug: Dapagliflozin
Tablet, Oral, 2.5 mg, Single-dose
Experimental: Dapagliflozin 5 mg Drug: Dapagliflozin
Tablet, Oral, 5 mg, Single-dose
Experimental: Dapagliflozin 10 mg Drug: Dapagliflozin
Tablet, Oral, 10 mg, Single-dose

Detailed Description:
Primary purpose: The primary purpose is to assess the pharmacokinetics of a single dose of Dapagliflozin in the range of 2.5 to 10 mg in pediatric subjects aged 10 to 17 years with T2DM
  Eligibility

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

Inclusion Criteria:

  • Clinical diagnosis of T2DM
  • Male and female subjects ages 10-17
  • Glycosylated Hemoglobin A1c (HbA1c) >6 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: NCT01525238

Locations
United States, Alabama
The Children Hospital Of Alabama
Birmingham, Alabama, United States, 35233
United States, California
Axis Clinical Trials
Los Angeles, California, United States, 90036
United States, Florida
Nemours Childrens Hospital
Orlando, Florida, United States, 32827
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Kentucky
Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States, 40202
United States, Louisiana
Lsuhsc-Shreveport
Shreveport, Louisiana, United States, 71103
United States, Missouri
Childrens Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, New York
Women And Children'S Hopsital Of Buffalo
Buffalo, New York, United States, 14222
United States, Ohio
Promedica Toledo Children'S Hospital
Toledo, Ohio, United States, 43606
Mercy Children'S Hospital
Toledo, Ohio, United States, 43608
United States, Pennsylvania
Children'S Hospital Of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children'S Hospital Of Pittsburgh Of Upmc
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Methodist Le Bonheur Hlthcare
Memphis, Tennessee, United States, 38103
United States, Texas
Christus Santa Rosa Childrens Hospital
San Antonio, Texas, United States, 78207
Mexico
Local Institution
Guadalajara, Jalisco, Mexico, 44150
Local Institution
Monterrey, Nuevo Leon, Mexico, 64460
Local Institution
Veracruz, Mexico, 91910
Sponsors and Collaborators
Bristol-Myers Squibb
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01525238     History of Changes
Other Study ID Numbers: MB102-091  2011-005225-40 
Study First Received: January 31, 2012
Results First Received: September 29, 2016
Last Updated: September 29, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on December 07, 2016