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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

January 31, 2012
September 29, 2016
July 2012
September 2014   (final data collection date for primary outcome measure)
  • 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)
  • Maximum observed plasma concentration (Cmax) of Dapagliflozin derived from plasma concentration versus time [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) of Dapagliflozin derived from plasma concentration versus time [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of Dapagliflozin derived from plasma concentration versus time [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of Dapagliflozin derived from plasma concentration versus time [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Plasma half-life (T-HALF) of Dapagliflozin derived from plasma concentration versus time [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Percent urinary recovery (%UR) of Dapagliflozin derived from urinary excretion data [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Renal clearance from time zero to 24 hours post-dose [CLR(0-24)] of Dapagliflozin derived from urinary excretion data [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Apparent clearance after extravascular administration (CL/F) of Dapagliflozin derived from urinary excretion data [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution at terminal phase after extravascular administration (Vz/F) of Dapagliflozin derived from urinary excretion data [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01525238 on ClinicalTrials.gov Archive Site
  • 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).

  • Safety: based on medical review of adverse event reports and the results of vital sign measurements, electrocardiograms (ECGs) and clinical laboratory tests [ Time Frame: 48 hours post dosing ] [ Designated as safety issue: Yes ]
  • Maximum observed plasma concentration (Cmax) of Dapagliflozin 3-O-Glucuronide [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) of Dapagliflozin 3-O-Glucuronide [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of Dapagliflozin 3-O-Glucuronide [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of Dapagliflozin 3-O-Glucuronide [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Plasma half-life (T-HALF) of Dapagliflozin 3-O-Glucuronide [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Percent urinary recovery (%UR) of Dapagliflozin 3-O-Glucuronide [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Renal clearance from time zero to 24 hours post-dose [CLR(0-24)] of Dapagliflozin 3-O-Glucuronide [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Apparent clearance after extravascular administration (CL/F) of Dapagliflozin 3-O-Glucuronide [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution at terminal phase after extravascular administration (Vz/F) of Dapagliflozin 3-O-Glucuronide [ Time Frame: Days 1-3 ] [ Designated as safety issue: No ]
  • Fasting plasma glucose concentration [ Time Frame: At pre-dose on Day 1 and Day 2 after an 8-hr fasting ] [ Designated as safety issue: No ]
  • Urinary glucose amounts [ Time Frame: First 24 h after Dapagliflozin administration ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
PK Study of Dapagliflozin in Pediatric Subjects With T2DM
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
The primary purpose of this study is to evaluate the pharmacokinetics (PK) of Dapagliflozin in pediatric subjects with type 2 diabetes mellitus (T2DM)
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
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Type 2 Diabetes Mellitus
  • Drug: Dapagliflozin
    Tablet, Oral, 2.5 mg, Single-dose
  • Drug: Dapagliflozin
    Tablet, Oral, 5 mg, Single-dose
  • Drug: Dapagliflozin
    Tablet, Oral, 10 mg, Single-dose
  • Experimental: Dapagliflozin 2.5 mg
    Intervention: Drug: Dapagliflozin
  • Experimental: Dapagliflozin 5 mg
    Intervention: Drug: Dapagliflozin
  • Experimental: Dapagliflozin 10 mg
    Intervention: Drug: Dapagliflozin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
53
September 2014
September 2014   (final data collection date for primary outcome measure)

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
Both
10 Years to 17 Years   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Mexico
 
NCT01525238
MB102-091, 2011-005225-40
No
Not Provided
Not Provided
Bristol-Myers Squibb
Bristol-Myers Squibb
AstraZeneca
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP