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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
53
Tablet, Oral, 2.5 mg, Single-dose
Tablet, Oral, 5 mg, Single-dose
Tablet, Oral, 10 mg, Single-dose
The Children Hospital Of Alabama
Birmingham, Alabama, United States
Axis Clinical Trials
Los Angeles, California, United States
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin
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).
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Median Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin
Time of maximum observed plasma concentration (Tmax) for Dapagliflozin was derived from plasma concentrations versus time data. Medians were reported in hours (h).
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Geometric Mean of Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Dapagliflozin
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).
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
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
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).
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Mean Plasma Half-life (T-HALF) of Dapagliflozin
Plasma half-life (T-Half) for Dapagliflozin was derived from plasma concentrations versus time data. Means are reported in hours.
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Nemours Childrens Hospital
Orlando, Florida, United States
Emory University
Atlanta, Georgia, United States
Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States
Lsuhsc-Shreveport
Shreveport, Louisiana, United States
Childrens Mercy Hospital
Kansas City, Missouri, United States
Women And Children'S Hopsital Of Buffalo
Buffalo, New York, United States
Promedica Toledo Children'S Hospital
Toledo, Ohio, United States
Mercy Children'S Hospital
Toledo, Ohio, United States
...and 7 more locations
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Geometric Mean of Apparent Clearance After Extravascular Administration (CL/F) of Dapagliflozin
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).
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Geometric Mean of Apparent Volume of Distribution at Terminal Phase After Extravascular Administration (Vz/F) of Dapagliflozin
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)
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin 3-O-Glucuronide
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).
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Median Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin 3-O-Glucuronide
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).
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Geometric Mean of Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Dapagliflozin 3-O-Glucuronide
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).
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
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
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).
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Mean Plasma Half-life (T-HALF) of Dapagliflozin 3-O-Glucuronide
Plasma half-life (T-Half) for Dapagliflozin was derived from plasma concentration versus time data. Means are reported in hours.
Time frame: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
Mean Fasting Plasma Glucose Concentrations at Pre-dose on Day 1 and on Day 2 After an 8-hr Fasting
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).
Time frame: Day 1 (Pre-dose) to Day 2
Mean Change in Fasting Plasma Glucose From Baseline Until Day 2
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).
Time frame: Day 1 (Pre-dose) to Day 2
Mean Total Amount of Glucose Excreted in Urine Over 24 Hours
The total amount of glucose excreted in urine was measured for 24 hours following administration of Dapagliflozin. Means are reported in grams.
Time frame: Time of dose to 24 hours post-dose, Day 1 to Day 2
Number of Participants With Vital Sign Abnormalities, Electrocardiogram (ECG) Abnormalities, or Physical Examination Abnormalities Following Study Drug Administration.
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.
Time frame: Day 1 to Day 3
Number of Participants With Marked Hematology Laboratory Abnormalities
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.
Time frame: Day 1 (Pre-dose) to Day 3
Number of Participants With Marked Serum Chemistry Abnormalities
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).
Time frame: Day 1 (Pre-dose) to Day 3
Number of Participants With Marked Abnormalities in Other Chemistry Testing
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)
Time frame: Day 1 (Pre-dose) to Day 3
Number of Participants With Marked Urinalysis Abnormalities
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).
Time frame: Day 1 (Pre-dose) to Day 3