PK Study of Dapagliflozin in Pediatric Subjects With T2DM
- Registration Number
- NCT01525238
- Lead Sponsor
- AstraZeneca
- Brief Summary
The primary purpose of this study is to evaluate the pharmacokinetics (PK) of Dapagliflozin in pediatric subjects with type 2 diabetes mellitus (T2DM)
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
- Clinical diagnosis of T2DM
- Male and female subjects ages 10-17
- Glycosylated Hemoglobin A1c (HbA1c) ≥6 to 10%
- Body weight ≥30 kg
- Fasting plasma glucose (FPG) >240 mg/dL at screening
- Abnormal renal function
- Active liver disease and/or significant abnormal liver function
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dapagliflozin 10 mg Dapagliflozin - Dapagliflozin 2.5 mg Dapagliflozin - Dapagliflozin 5 mg Dapagliflozin -
- Primary Outcome Measures
Name Time Method Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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 Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Dapagliflozin 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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 Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Dapagliflozin 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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 Apparent Volume of Distribution at Terminal Phase After Extravascular Administration (Vz/F) of Dapagliflozin 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 of Dapagliflozin was derived from plasma concentration versus time data. Geometric means are reported in Liters (L)
- Secondary Outcome Measures
Name Time Method Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin 3-O-Glucuronide 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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 Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-T)] of Dapagliflozin 3-O-Glucuronide 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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).
Geometric Mean of Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Dapagliflozin 3-O-Glucuronide 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose 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).
Mean Fasting Plasma Glucose Concentrations at Pre-dose on Day 1 and on Day 2 After an 8-hr Fasting Day 1 (Pre-dose) to 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. Means are reported in milligrams per deciliter (mg/dL).
Mean Change in Fasting Plasma Glucose From Baseline Until Day 2 Day 1 (Pre-dose) to 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).
Number of Participants With Marked Abnormalities in Other Chemistry Testing Day 1 (Pre-dose) to Day 3 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 Day 1 (Pre-dose) to Day 3 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).
Mean Plasma Half-life (T-HALF) of Dapagliflozin 3-O-Glucuronide 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose Plasma half-life (T-Half) for Dapagliflozin was derived from plasma concentration versus time data. Means are reported in hours.
Mean Total Amount of Glucose Excreted in Urine Over 24 Hours Time of dose to 24 hours post-dose, Day 1 to Day 2 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. Day 1 to Day 3 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 Day 1 (Pre-dose) to Day 3 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 Day 1 (Pre-dose) to Day 3 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).
Trial Locations
- Locations (15)
Emory University
🇺🇸Atlanta, Georgia, United States
Lsuhsc-Shreveport
🇺🇸Shreveport, Louisiana, United States
Children'S Hospital Of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children'S Hospital Of Pittsburgh Of Upmc
🇺🇸Pittsburgh, Pennsylvania, United States
Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Mercy Children'S Hospital
🇺🇸Toledo, Ohio, United States
Kosair Charities Pediatric Clinical Research Unit
🇺🇸Louisville, Kentucky, United States
Christus Santa Rosa Childrens Hospital
🇺🇸San Antonio, Texas, United States
Nemours Childrens Hospital
🇺🇸Orlando, Florida, United States
Promedica Toledo Children'S Hospital
🇺🇸Toledo, Ohio, United States
Women And Children'S Hopsital Of Buffalo
🇺🇸Buffalo, New York, United States
Local Institution
🇲🇽Veracruz, Mexico
Axis Clinical Trials
🇺🇸Los Angeles, California, United States
The Children Hospital Of Alabama
🇺🇸Birmingham, Alabama, United States
Methodist Le Bonheur Hlthcare
🇺🇸Memphis, Tennessee, United States