Trial Outcomes & Findings for PK Study of Dapagliflozin in Pediatric Subjects With T2DM (NCT NCT01525238)

NCT ID: NCT01525238

Last Updated: 2017-05-30

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 53 participants
• Primary outcome timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose
• Results posted on: 2017-05-30

Participant Flow

53 participants enrolled; 24 randomized; 24 treated with study drug. 29 participants were not randomized due to no longer meeting study criteria (25), withdrawal of consent (2), or other reasons (2).

Participant milestones

Measure	Dapagliflozin 2.5 mg Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Overall Study STARTED	8	8	8
Overall Study COMPLETED	7	8	8
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Measure	Dapagliflozin 2.5 mg Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Overall Study Withdrawal by Subject	1	0	0

Baseline Characteristics

PK Study of Dapagliflozin in Pediatric Subjects With T2DM

Baseline characteristics by cohort

Measure	Dapagliflozin 2.5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose	Total n=24 Participants Total of all reporting groups
Age, Continuous	15.0 years STANDARD_DEVIATION 1.69 • n=5 Participants	14.0 years STANDARD_DEVIATION 2.39 • n=7 Participants	14.6 years STANDARD_DEVIATION 2.13 • n=5 Participants	14.5 years STANDARD_DEVIATION 2.04 • n=4 Participants
Age, Customized 10 to <= 15 years	5 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	14 participants n=4 Participants
Age, Customized 16 to <= 17 years	3 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	10 participants n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable pharmacokinetic (PK) profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin	24.8 ng/mL Geometric Coefficient of Variation 34	48.4 ng/mL Geometric Coefficient of Variation 41	118 ng/mL Geometric Coefficient of Variation 35

PRIMARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles.

Time of maximum observed plasma concentration (Tmax) for Dapagliflozin was derived from plasma concentrations versus time data. Medians were reported in hours (h).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Median Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin	1.50 hours Interval 0.75 to 2.0	0.960 hours Interval 0.58 to 1.53	0.875 hours Interval 0.75 to 4.0

PRIMARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Geometric Mean of Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinite Time [AUC(INF)] of Dapagliflozin	101 ng*h/mL Geometric Coefficient of Variation 23	199 ng*h/mL Geometric Coefficient of Variation 29	427 ng*h/mL Geometric Coefficient of Variation 31

PRIMARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-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	92.3 ng*h/mL Geometric Coefficient of Variation 27	189 ng*h/mL Geometric Coefficient of Variation 31	418 ng*h/mL Geometric Coefficient of Variation 31

PRIMARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

Plasma half-life (T-Half) for Dapagliflozin was derived from plasma concentrations versus time data. Means are reported in hours.

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Mean Plasma Half-life (T-HALF) of Dapagliflozin	14.1 hours Standard Deviation 5.59	10.3 hours Standard Deviation 3.72	10.7 hours Standard Deviation 2.16

PRIMARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Geometric Mean of Apparent Clearance After Extravascular Administration (CL/F) of Dapagliflozin	413 mL/min Geometric Coefficient of Variation 26	418 mL/min Geometric Coefficient of Variation 27	391 mL/min Geometric Coefficient of Variation 25

PRIMARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

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)

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Geometric Mean of Apparent Volume of Distribution at Terminal Phase After Extravascular Administration (Vz/F) of Dapagliflozin	468 Liters Geometric Coefficient of Variation 34	343 Liters Geometric Coefficient of Variation 45	355 Liters Geometric Coefficient of Variation 34

SECONDARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin 3-O-Glucuronide	24.6 ng/mL Geometric Coefficient of Variation 45	49.0 ng/mL Geometric Coefficient of Variation 50	154 ng/mL Geometric Coefficient of Variation 27

SECONDARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Median Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin 3-O-Glucuronide	1.50 hours Interval 1.0 to 4.0	1.50 hours Interval 0.83 to 4.0	1.50 hours Interval 1.47 to 4.0

SECONDARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-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	105 ng*hr/mL Geometric Coefficient of Variation 23	232 ng*hr/mL Geometric Coefficient of Variation 30	658 ng*hr/mL Geometric Coefficient of Variation 21

SECONDARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-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	95.8 ng*h/mL Geometric Coefficient of Variation 20	208 ng*h/mL Geometric Coefficient of Variation 32	612 ng*h/mL Geometric Coefficient of Variation 24

SECONDARY outcome

Timeframe: 11 time points: Immediately pre-dose, 0.5, 0.75, 1.0, 1.5, 4, 8, 12, 14, 24, and 48 hours post-dose

Population: All treated participants with evaluable PK profiles

Plasma half-life (T-Half) for Dapagliflozin was derived from plasma concentration versus time data. Means are reported in hours.

Outcome measures

Measure	Dapagliflozin 2.5 mg n=7 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Mean Plasma Half-life (T-HALF) of Dapagliflozin 3-O-Glucuronide	4.62 hours Standard Deviation 3.086	8.71 hours Standard Deviation 2.024	8.37 hours Standard Deviation 3.330

SECONDARY outcome

Timeframe: Day 1 (Pre-dose) to Day 2

Population: All treated participants with evaluable pharmacodynamic (PD) profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=6 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Mean Fasting Plasma Glucose Concentrations at Pre-dose on Day 1 and on Day 2 After an 8-hr Fasting Day 1 Pre-dose (n= 6, 8, 8)	146.2 mg/dL Standard Deviation 72.56	152.1 mg/dL Standard Deviation 49.06	139.8 mg/dL Standard Deviation 39.63
Mean Fasting Plasma Glucose Concentrations at Pre-dose on Day 1 and on Day 2 After an 8-hr Fasting Day 2 after 8 hour fast (n= 3, 8, 7)	124.0 mg/dL Standard Deviation 45.21	119.4 mg/dL Standard Deviation 17.18	119.0 mg/dL Standard Deviation 29.15

SECONDARY outcome

Timeframe: Day 1 (Pre-dose) to Day 2

Population: All treated participants with evaluable PD profiles

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=3 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=7 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Mean Change in Fasting Plasma Glucose From Baseline Until Day 2	-46.7 mg/dL Standard Deviation 60.08	-32.8 mg/dL Standard Deviation 42.41	-22.0 mg/dL Standard Deviation 27.32

SECONDARY outcome

Timeframe: Time of dose to 24 hours post-dose, Day 1 to Day 2

Population: All treated participants with evaluable PD profiles

The total amount of glucose excreted in urine was measured for 24 hours following administration of Dapagliflozin. Means are reported in grams.

Outcome measures

Measure	Dapagliflozin 2.5 mg n=5 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=7 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Mean Total Amount of Glucose Excreted in Urine Over 24 Hours	52.84 grams Standard Deviation 27.18	62.39 grams Standard Deviation 26.55	89.04 grams Standard Deviation 41.25

SECONDARY outcome

Timeframe: Day 1 to Day 3

Population: All treated participants

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.

Outcome measures

Measure	Dapagliflozin 2.5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Number of Participants With Vital Sign Abnormalities, Electrocardiogram (ECG) Abnormalities, or Physical Examination Abnormalities Following Study Drug Administration. Vital sign abnormalities	0 participants	0 participants	0 participants
Number of Participants With Vital Sign Abnormalities, Electrocardiogram (ECG) Abnormalities, or Physical Examination Abnormalities Following Study Drug Administration. ECG abnormalities	0 participants	0 participants	0 participants
Number of Participants With Vital Sign Abnormalities, Electrocardiogram (ECG) Abnormalities, or Physical Examination Abnormalities Following Study Drug Administration. Physical examination abnormalities	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 (Pre-dose) to Day 3

Population: All treated participants

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.

Outcome measures

Measure	Dapagliflozin 2.5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Number of Participants With Marked Hematology Laboratory Abnormalities Leukocytes, low (n=8, 8, 8)	1 participants	0 participants	1 participants
Number of Participants With Marked Hematology Laboratory Abnormalities Neutrophils, low (n=8, 8, 8)	0 participants	0 participants	1 participants

SECONDARY outcome

Timeframe: Day 1 (Pre-dose) to Day 3

Population: All treated participants

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Number of Participants With Marked Serum Chemistry Abnormalities ALT, high (8, 8, 8)	1 participants	0 participants	0 participants
Number of Participants With Marked Serum Chemistry Abnormalities AST, high (n=8, 8, 8)	1 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 (Pre-dose) to Day 3

Population: All treated participants

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)

Outcome measures

Measure	Dapagliflozin 2.5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Number of Participants With Marked Abnormalities in Other Chemistry Testing Glucose, fasting serum, high (n=7, 7, 7)	1 participants	1 participants	0 participants
Number of Participants With Marked Abnormalities in Other Chemistry Testing Additional other chemistry marked abnormalities	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 (Pre-dose) to Day 3

Population: All treated participants with evaluable lab results

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).

Outcome measures

Measure	Dapagliflozin 2.5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 Participants Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 Participants Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Number of Participants With Marked Urinalysis Abnormalities WBC, urine, high (n=4, 2, 3)	1 participants	0 participants	1 participants
Number of Participants With Marked Urinalysis Abnormalities Blood, urine, high (n=8, 8, 8)	0 participants	0 participants	2 participants
Number of Participants With Marked Urinalysis Abnormalities Glucose, urine, high (n=8, 8, 8)	2 participants	3 participants	4 participants
Number of Participants With Marked Urinalysis Abnormalities Protein, urine, high (n=8, 8, 8)	0 participants	0 participants	3 participants
Number of Participants With Marked Urinalysis Abnormalities RBC, urine, high (n=1, 1, 4)	0 participants	0 participants	3 participants

Adverse Events

Dapagliflozin 2.5 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Dapagliflozin 5 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Dapagliflozin 10 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Dapagliflozin 2.5 mg n=8 participants at risk Dapagliflozin: Tablet, Oral, 2.5 mg, Single-dose	Dapagliflozin 5 mg n=8 participants at risk Dapagliflozin: Tablet, Oral, 5 mg, Single-dose	Dapagliflozin 10 mg n=8 participants at risk Dapagliflozin: Tablet, Oral, 10 mg, Single-dose
Investigations Neutrophil count decreased	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	12.5% 1/8 • Number of events 1 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.
General disorders Peripheral swelling	12.5% 1/8 • Number of events 1 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	12.5% 1/8 • Number of events 1 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.
Gastrointestinal disorders Nausea	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	12.5% 1/8 • Number of events 2 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.
Gastrointestinal disorders Vomiting	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	12.5% 1/8 • Number of events 2 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.
Renal and urinary disorders Pollakiuria	12.5% 1/8 • Number of events 1 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.
Skin and subcutaneous tissue disorders Rash	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	12.5% 1/8 • Number of events 1 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.
Skin and subcutaneous tissue disorders Skin irritation	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	12.5% 1/8 • Number of events 1 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	0.00% 0/8 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.	12.5% 1/8 • Number of events 1 • SAEs collected from Screening (up to 28 days before first dose) to 30 days after last dose; Non-serious AEs collected from time of dose (Day 1) to Study Discharge (Day 3) and followed until resolution, stabilization, or reclassification as SAE.

Additional Information

Anna Maria Langkilde

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place