Trial Outcomes & Findings for Study of MEDI0382 in Combination With Dapagliflozin and Metformin in Overweight/Obese Participants With Type 2 Diabetes (NCT NCT03444584)

NCT ID: NCT03444584

Last Updated: 2020-01-13

Results Overview

The MMTT test involved the consumption of a standardised liquid meal (nutritional supplement of fat, carbohydrate, and protein) within 5 minutes. On Day -1 and on Day 28, following a minimum 10 hour fast, serial of blood samples were obtained prior and through 240 minutes after consumption of standardized meal for the measurement of glucose metabolism (with no additional food intake during this time).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 49 participants
• Primary outcome timeframe: Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -1 (Baseline) and Day 28
• Results posted on: 2020-01-13

Participant Flow

The study was conducted in Germany and Hungary between 08May2018 and 06Dec2018.

Participant milestones

Measure	Placebo Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Overall Study STARTED	24	25
Overall Study COMPLETED	24	23
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Placebo Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Overall Study Withdrawal by Subject	0	1
Overall Study Other	0	1

Baseline Characteristics

Study of MEDI0382 in Combination With Dapagliflozin and Metformin in Overweight/Obese Participants With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	TOTAL n=49 Participants Total of all reporting groups
Age, Continuous	58.4 Years STANDARD_DEVIATION 10.0 • n=5 Participants	61.0 Years STANDARD_DEVIATION 8.2 • n=7 Participants	59.7 Years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	25 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -1 (Baseline) and Day 28

Population: Intent-to-treat (ITT) population included all participants who received any dose of study drugs analyzed according to their randomized treatment group. Here, number of participants analyzed "N" signifies participants who were analyzed for the specified outcome measure.

The MMTT test involved the consumption of a standardised liquid meal (nutritional supplement of fat, carbohydrate, and protein) within 5 minutes. On Day -1 and on Day 28, following a minimum 10 hour fast, serial of blood samples were obtained prior and through 240 minutes after consumption of standardized meal for the measurement of glucose metabolism (with no additional food intake during this time).

Outcome measures

Measure	Placebo n=22 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=24 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline to Day 28 in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4hrs) as Measured by Mixed-meal Tolerance Test (MMTT)	-11.28 hr·mg/dL Interval -51.05 to 28.5	-154.37 hr·mg/dL Interval -192.45 to -116.29

PRIMARY outcome

Timeframe: Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -1 (Baseline) and Day 28

Population: An ITT population included all participants who received any dose of study drugs and analyzed according to their randomized treatment group. Here, number of participants analyzed "N" signifies participants who were analyzed for the specified outcome measure.

The MMTT test involved the consumption of a standardised liquid meal (nutritional supplement of fat, carbohydrate, and protein)within 5 minutes. On Day -1 and on Day 28, following a minimum 10-hour fast, serial of blood samples were obtained prior and through 240 minutes after consumption of standardized meal for the measurement of glucose metabolism (with no additional food intake during this time).

Outcome measures

Measure	Placebo n=22 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=24 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Percent Change From Baseline to Day 28 in Plasma Glucose AUC0-4hrs as Measured by MMTT	-0.13 Percent change in Glucose AUC0-4hrs Interval -5.96 to 5.69	-22.30 Percent change in Glucose AUC0-4hrs Interval -27.88 to -16.73

SECONDARY outcome

Timeframe: Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience(immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TEAEs	14 Participants	13 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TESAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal 12-lead ECG reported as TEAEs are reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Reported as TEAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal vital signs reported as TEAEs are reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Number of Participants With Abnormal Vital Signs Reported as TEAEs Tachycardia paroxysmal	1 Participants	0 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Tachycardia	2 Participants	1 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Palpitations	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal physical examinations reported as TEAEs are reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Number of Participants With Abnormal Physical Examinations Reported as TEAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

Population: As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Hypoglycemia	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

Population: MEDI0382 pharmacokinetic (PK) population included all participants who received at least 1 dose of MEDI0382 and had at least 1 MEDI0382 PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Area under the plasma concentration time curve from time zero to infinity (AUC [0-∞]) of MEDI0382 is reported.

Outcome measures

Measure	Placebo n=25 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of MEDI0382 Day 7 (MEDI0382 100 µg)	106.4 ng.hr/mL Interval 57.7 to 251.8	—
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of MEDI0382 Day 14 ( MEDI0382 200 µg)	196.7 ng.hr/mL Interval 99.4 to 472.0	—
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of MEDI0382 Day 28 (MEDI0382 300 µg)	314.6 ng.hr/mL Interval 211.0 to 537.3	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

Population: Dapagliflozin PK population included all participants who received at least 1 dose of dapagliflozin and had at least 1 dapagliflozin PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Area under the plasma concentration time curve from time zero to infinity (AUC [0-∞]) of Dapagliflozin is reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of Dapagliflozin Day -1	432.6 ng.hr/mL Interval 271.5 to 918.6	473.8 ng.hr/mL Interval 288.8 to 1073.2
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of Dapagliflozin Day 7	410.2 ng.hr/mL Interval 209.9 to 1024.2	438.0 ng.hr/mL Interval 222.2 to 833.6
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of Dapagliflozin Day 14	421.0 ng.hr/mL Interval 219.0 to 1327.8	448.6 ng.hr/mL Interval 247.0 to 615.9
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC [0-∞]) of Dapagliflozin Day 28	405.7 ng.hr/mL Interval 261.1 to 799.5	523.4 ng.hr/mL Interval 319.5 to 946.0

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

Population: MEDI0382 PK population included all participants who received at least 1 dose of MEDI0382 and had at least 1 MEDI0382 PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Area under the plasma concentration-time curve during the dosing period (AUCtau) of MEDI0382 is reported.

Outcome measures

Measure	Placebo n=25 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of MEDI0382 Day 7 (MEDI0382 100 µg)	89.6 ng.hr/mL Interval 43.1 to 199.4	—
Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of MEDI0382 Day 14 ( MEDI0382 200 µg)	165.0 ng.hr/mL Interval 86.9 to 365.5	—
Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of MEDI0382 Day 28 (MEDI0382 300 µg)	265.9 ng.hr/mL Interval 101.7 to 795.1	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

Population: Dapagliflozin PK population included all participants who received at least 1 dose of dapagliflozin and had at least 1 dapagliflozin PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Area under the plasma Concentration-time curve during the dosing period (AUCtau) of Dapagliflozin is reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of Dapagliflozin Day -1	400.9 ng.hr/mL Interval 182.4 to 1011.5	430.3 ng.hr/mL Interval 252.5 to 815.2
Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of Dapagliflozin Day 7	377.5 ng.hr/mL Interval 76.4 to 910.7	406.8 ng.hr/mL Interval 211.5 to 1142.6
Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of Dapagliflozin Day 14	417.1 ng.hr/mL Interval 209.0 to 1107.7	396.8 ng.hr/mL Interval 215.4 to 669.7
Area Under the Plasma Concentration-time Curve During the Dosing Period (AUCtau) of Dapagliflozin Day 28	423.1 ng.hr/mL Interval 180.6 to 977.3	463.8 ng.hr/mL Interval 284.3 to 1245.7

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

Population: MEDI0382 PK population included all participants who received at least 1 dose of MEDI0382 and had at least 1 MEDI0382 PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Maximum observed serum concentration (Cmax) of MEDI0382 is reported.

Outcome measures

Measure	Placebo n=25 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 7 (MEDI0382 100 µg)	5.2 ng/mL Interval 2.7 to 11.9	—
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 14 ( MEDI0382 200 µg)	10.1 ng/mL Interval 4.4 to 21.7	—
Maximum Observed Serum Concentration (Cmax) of MEDI0382 Day 28 (MEDI0382 300 µg)	17.2 ng/mL Interval 6.1 to 45.4	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

Population: Dapagliflozin PK population included all participants who received at least 1 dose of dapagliflozin and had at least 1 dapagliflozin PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Maximum observed serum concentration (Cmax) of Dapagliflozin is reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Maximum Observed Serum Concentration (Cmax) of Dapagliflozin Day -1	110.1 ng/mL Interval 46.3 to 208.3	116.7 ng/mL Interval 38.2 to 206.8
Maximum Observed Serum Concentration (Cmax) of Dapagliflozin Day 7	92.0 ng/mL Interval 5.2 to 256.7	84.4 ng/mL Interval 24.1 to 211.7
Maximum Observed Serum Concentration (Cmax) of Dapagliflozin Day 14	95.6 ng/mL Interval 33.5 to 280.7	61.1 ng/mL Interval 15.8 to 149.9
Maximum Observed Serum Concentration (Cmax) of Dapagliflozin Day 28	112.2 ng/mL Interval 47.0 to 235.4	94.2 ng/mL Interval 25.2 to 182.2

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

Population: MEDI0382 PK population included all participants who received at least 1 dose of MEDI0382 and had at least 1 MEDI0382 PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Time to reach maximum observed serum concentration (Tmax) of MEDI0382 is reported.

Outcome measures

Measure	Placebo n=25 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI0382 Day 7 (MEDI0382 100 µg)	5.5 Hours Interval 2.0 to 8.0	—
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI0382 Day 14 ( MEDI0382 200 µg)	5.1 Hours Interval 2.0 to 8.0	—
Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI0382 Day 28 (MEDI0382 300 µg)	4 Hours Interval 1.9 to 8.1	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

Population: Dapagliflozin PK population included all participants who received at least 1 dose of dapagliflozin and had at least 1 dapagliflozin PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Time to reach maximum observed serum concentration (Tmax) of Dapagliflozin is reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Time to Reach Maximum Observed Serum Concentration (Tmax) of Dapagliflozin Day -1	1 Hours Interval 0.5 to 2.0	1 Hours Interval 0.4 to 23.9
Time to Reach Maximum Observed Serum Concentration (Tmax) of Dapagliflozin Day 7	1 Hours Interval 0.5 to 11.4	1 Hours Interval 0.5 to 4.0
Time to Reach Maximum Observed Serum Concentration (Tmax) of Dapagliflozin Day 14	1.1 Hours Interval 0.5 to 6.0	1 Hours Interval 0.0 to 8.1
Time to Reach Maximum Observed Serum Concentration (Tmax) of Dapagliflozin Day 28	1 Hours Interval 0.2 to 1.8	1 Hours Interval 0.5 to 8.1

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

Population: MEDI0382 PK population included all participants who received at least 1 dose of MEDI0382 and had at least 1 MEDI0382 PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Terminal half-life is the time required for the plasma concentration to fall by 50% during the terminal phase. The t½ of MEDI0382 is reported.

Outcome measures

Measure	Placebo n=25 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Terminal Elimination Half-life (t½) of MEDI0382 Day 7 (MEDI0382 100 µg)	8.8 Hours Interval 6.1 to 11.9	—
Terminal Elimination Half-life (t½) of MEDI0382 Day 14 ( MEDI0382 200 µg)	9 Hours Interval 5.6 to 11.8	—
Terminal Elimination Half-life (t½) of MEDI0382 Day 28 (MEDI0382 300 µg)	9.1 Hours Interval 5.1 to 11.6	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

Population: Dapagliflozin PK population included all participants who received at least 1 dose of dapagliflozin and had at least 1 dapagliflozin PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Terminal half-life is the time required for the plasma concentration to fall by 50% during the terminal phase. The t½ of Dapagliflozin is reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Terminal Elimination Half-life (t½) of Dapagliflozin Day -1	8.2 Hours Interval 5.3 to 11.2	7.8 Hours Interval 5.4 to 11.3
Terminal Elimination Half-life (t½) of Dapagliflozin Day 7	7.9 Hours Interval 4.1 to 10.4	8.3 Hours Interval 5.8 to 11.1
Terminal Elimination Half-life (t½) of Dapagliflozin Day 14	7.0 Hours Interval 5.1 to 11.4	8.5 Hours Interval 7.0 to 10.0
Terminal Elimination Half-life (t½) of Dapagliflozin Day 28	7.6 Hours Interval 5.8 to 11.0	9.1 Hours Interval 6.1 to 11.8

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days 7, 14, and 28

Population: MEDI0382 PK population included all participants who received at least 1 dose of MEDI0382 and had at least 1 MEDI0382 PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The CL/F of MEDI0382 is reported.

Outcome measures

Measure	Placebo n=25 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Apparent Clearance (CL/F) of MEDI0382 Day 7 (MEDI0382 100 µg)	1.1 L/hr Interval 0.5 to 1.9	—
Apparent Clearance (CL/F) of MEDI0382 Day 14 ( MEDI0382 200 µg)	1.3 L/hr Interval 0.5 to 2.2	—
Apparent Clearance (CL/F) of MEDI0382 Day 28 (MEDI0382 300 µg)	1.2 L/hr Interval 0.8 to 1.8	—

SECONDARY outcome

Timeframe: Pre-dose and 0.5, 1, 2, 4, 6, 8, 12, and 24 hrs post-dose on Days -1, 7, 14, and 28

Population: Dapagliflozin PK population included all participants who received at least 1 dose of dapagliflozin and had at least 1 dapagliflozin PK sample above the lower limit of quantitation. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The CL/F of Dapagliflozin is reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Apparent Clearance (CL/F) of Dapagliflozin Day -1	25.5 L/Hr Interval 13.3 to 38.9	23.3 L/Hr Interval 12.3 to 39.6
Apparent Clearance (CL/F) of Dapagliflozin Day 7	26.7 L/Hr Interval 11.0 to 52.8	25.7 L/Hr Interval 14.2 to 47.3
Apparent Clearance (CL/F) of Dapagliflozin Day 14	25.9 L/Hr Interval 9.0 to 47.7	25.5 L/Hr Interval 18.8 to 46.4
Apparent Clearance (CL/F) of Dapagliflozin Day 28	26.8 L/Hr Interval 13.8 to 40.2	22.2 L/Hr Interval 13.4 to 35.2

SECONDARY outcome

Timeframe: Day 1 (pre-dose), on Day 29 , and 28 days post last dose (end of study visit; approximately 8 weeks)

Population: Immunogenicity population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to the treatment they actually received and had at least one serum sample for immunogenicity testing. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Number of participants with positive Anti-drug antibodies (ADA) titer to MEDI0382 are reported.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI0382 Day 1	0 Participants	3 Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI0382 Day 29	0 Participants	1 Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) Titer to MEDI0382 End of Study	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

Population: An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline in Plasma Glucose AUC24-hrs to the End of Each Dosing Level as Measured by Continuous Glucose Monitoring (CGM) Day 7 (MEDI0382 100 μg)	49.14 hr.mg/dL Standard Deviation 667.30	-832.66 hr.mg/dL Standard Deviation 506.22
Change From Baseline in Plasma Glucose AUC24-hrs to the End of Each Dosing Level as Measured by Continuous Glucose Monitoring (CGM) Day 14 (MEDI0382 200 μg)	57.30 hr.mg/dL Standard Deviation 379.95	-666.05 hr.mg/dL Standard Deviation 647.63
Change From Baseline in Plasma Glucose AUC24-hrs to the End of Each Dosing Level as Measured by Continuous Glucose Monitoring (CGM) Day 28 (MEDI0382 300 μg)	229.47 hr.mg/dL Standard Deviation 589.19	-726.85 hr.mg/dL Standard Deviation 710.71

SECONDARY outcome

Timeframe: Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

Population: An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline in Mean 24-hrs Plasma Glucose to the End of Each Dosing Level as Measured by CGM Day 7 (MEDI0382 100 μg)	2.59 mg/dL Standard Deviation 28.96	-34.74 mg/dL Standard Deviation 20.34
Change From Baseline in Mean 24-hrs Plasma Glucose to the End of Each Dosing Level as Measured by CGM Day 14 (MEDI0382 200 μg)	2.83 mg/dL Standard Deviation 17.01	-28.34 mg/dL Standard Deviation 27.12
Change From Baseline in Mean 24-hrs Plasma Glucose to the End of Each Dosing Level as Measured by CGM Day 28 (MEDI0382 300 μg)	9.70 mg/dL Standard Deviation 24.73	-30.55 mg/dL Standard Deviation 29.82

SECONDARY outcome

Timeframe: Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

Population: An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline in Standard Deviation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM Day 7 (MEDI0382 100 μg)	-3.01 mg/dL Standard Deviation 13.84	-7.21 mg/dL Standard Deviation 11.05
Change From Baseline in Standard Deviation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM Day 14 (MEDI0382 200 μg)	1.38 mg/dL Standard Deviation 9.47	-7.52 mg/dL Standard Deviation 9.73
Change From Baseline in Standard Deviation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM Day 28 (MEDI0382 300 μg)	-4.39 mg/dL Standard Deviation 10.67	-9.76 mg/dL Standard Deviation 10.18

SECONDARY outcome

Timeframe: Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

Population: An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline in Coefficient of Variation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM Day 7 (MEDI0382 100 μg)	-2.37 Percent of coefficient of variation Standard Deviation 9.06	-0.45 Percent of coefficient of variation Standard Deviation 6.68
Change From Baseline in Coefficient of Variation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM Day 14 (MEDI0382 200 μg)	0.96 Percent of coefficient of variation Standard Deviation 8.74	-2.06 Percent of coefficient of variation Standard Deviation 6.59
Change From Baseline in Coefficient of Variation of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM Day 28 (MEDI0382 300 μg)	-4.26 Percent of coefficient of variation Standard Deviation 7.16	-3.21 Percent of coefficient of variation Standard Deviation 7.25

SECONDARY outcome

Timeframe: Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

Population: An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg.

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline in Mean Amplitude of Glucose Excursions (MAGE) of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM Day 7 (MEDI0382 100 μg)	-13.46 mg/dL Standard Deviation 32.07	-25.74 mg/dL Standard Deviation 35.06
Change From Baseline in Mean Amplitude of Glucose Excursions (MAGE) of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM Day 14 (MEDI0382 200 μg)	18.05 mg/dL Standard Deviation 47.60	-26.59 mg/dL Standard Deviation 25.60
Change From Baseline in Mean Amplitude of Glucose Excursions (MAGE) of 24-hrs Plasma Glucose Readings to the End of Each Dosing Level as Measured by CGM Day 28 (MEDI0382 300 μg)	-8.09 mg/dL Standard Deviation 27.68	-27.92 mg/dL Standard Deviation 23.17

SECONDARY outcome

Timeframe: Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

Population: An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg. Euglycemic range is defined as glucose levels of >= 70 mg/dL (>= 3.9 mmol/L) and <= 180 mg/dL (<= 10.0 mmol/L).

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Euglycemic Range to the End of Each Dosing as Measured by CGM Day 7 (MEDI0382 100 μg)	-5.61 Percent of Euglycemic Range Standard Deviation 19.65	7.12 Percent of Euglycemic Range Standard Deviation 20.60
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Euglycemic Range to the End of Each Dosing as Measured by CGM Day 14 (MEDI0382 200 μg)	-2.79 Percent of Euglycemic Range Standard Deviation 10.16	5.31 Percent of Euglycemic Range Standard Deviation 17.71
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Euglycemic Range to the End of Each Dosing as Measured by CGM Day 28 (MEDI0382 300 μg)	-4.17 Percent of Euglycemic Range Standard Deviation 15.80	6.54 Percent of Euglycemic Range Standard Deviation 24.37

SECONDARY outcome

Timeframe: Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

Population: An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg. Hyperglycemic (high glucose) range is defined as glucose levels of > 180 mg/dL (> 10.0 mmol/L).

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hyperglycemic Range to the End of Each Dosing as Measured by CGM Day 7 (MEDI0382 100 μg)	3.62 Percent of hyperglycemic range Standard Deviation 17.80	-13.99 Percent of hyperglycemic range Standard Deviation 14.95
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hyperglycemic Range to the End of Each Dosing as Measured by CGM Day 14 (MEDI0382 200 μg)	0.36 Percent of hyperglycemic range Standard Deviation 10.50	-9.81 Percent of hyperglycemic range Standard Deviation 13.68
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hyperglycemic Range to the End of Each Dosing as Measured by CGM Day 28 (MEDI0382 300 μg)	6.08 Percent of hyperglycemic range Standard Deviation 16.96	-9.72 Percent of hyperglycemic range Standard Deviation 20.97

SECONDARY outcome

Timeframe: Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

Population: An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg. Hypoglycemic range is defined as glucose levels of < 70 mg/dL (< 3.9 mmol/L).

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hypoglycemic Range to the End of Each Dosing as Measured by CGM Day 7 (MEDI0382 100 μg)	1.17 Percent of hypoglycemic range Standard Deviation 5.64	6.08 Percent of hypoglycemic range Standard Deviation 10.36
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hypoglycemic Range to the End of Each Dosing as Measured by CGM Day 14 (MEDI0382 200 μg)	2.00 Percent of hypoglycemic range Standard Deviation 3.79	3.44 Percent of hypoglycemic range Standard Deviation 12.72
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within the Hypoglycemic Range to the End of Each Dosing as Measured by CGM Day 28 (MEDI0382 300 μg)	-2.08 Percent of hypoglycemic range Standard Deviation 4.14	2.84 Percent of hypoglycemic range Standard Deviation 12.20

SECONDARY outcome

Timeframe: Day -1 (Baseline) through Day 7 for MEDI0382 100 μg, Day 14 for MEDI0382 200 μg, and Day 28 for MEDI0382 300 μg

Population: An ITT population included all participants who received any dose of study drug (MEDI0382 or placebo) and analyzed according to their randomized treatment group. Here, number analyzed "n" signifies participants who were analyzed for the specified day.

Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Continuous glucose monitoring measures glucose excursions during different meals and at different times of the day. End of dosing: Day 7 for MEDI0382 100 μg; Day 14 for MEDI0382 200 μg; and Day 28 for MEDI0382 300 μg. Clinically significant hypoglycemic range is defined as glucose levels of < 54 mg/dL (3.0 mmol/L).

Outcome measures

Measure	Placebo n=24 Participants Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 Participants Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within Clinically Significant Hypoglycemic Range to the End of Each Dosing as Measured by CGM Day 7 (MEDI0382 100 μg)	0.76 Percent of hypoglycemic range Standard Deviation 3.64	1.61 Percent of hypoglycemic range Standard Deviation 5.03
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within Clinically Significant Hypoglycemic Range to the End of Each Dosing as Measured by CGM Day 14 (MEDI0382 200 μg)	0.27 Percent of hypoglycemic range Standard Deviation 1.19	-0.06 Percent of hypoglycemic range Standard Deviation 2.18
Change From Baseline in the Percentage of 24-hrs Glucose Readings That Falls Within Clinically Significant Hypoglycemic Range to the End of Each Dosing as Measured by CGM Day 28 (MEDI0382 300 μg)	-0.26 Percent of hypoglycemic range Standard Deviation 0.90	0.93 Percent of hypoglycemic range Standard Deviation 4.91

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

MEDI0382

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=24 participants at risk Participants received subcutaneous dose of placebo matched to MEDI0382 daily for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.	MEDI0382 n=25 participants at risk Participants received subcutaneous dose of MEDI0382 daily (titrated up from 100 μg for 7 days to 200 μg for 7 days and to 300 μg for 14 days) for 28 days. Participants were on metformin and dapagliflozin background dual therapy during the treatment period.
Cardiac disorders Tachycardia	8.3% 2/24 • Number of events 2 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 3 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	12.0% 3/25 • Number of events 5 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Gastrointestinal disorders Constipation	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	12.0% 3/25 • Number of events 3 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Gastrointestinal disorders Diarrhoea	8.3% 2/24 • Number of events 2 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Gastrointestinal disorders Nausea	8.3% 2/24 • Number of events 4 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	20.0% 5/25 • Number of events 7 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Gastrointestinal disorders Vomiting	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	20.0% 5/25 • Number of events 6 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Infections and infestations Viral upper respiratory tract infection	12.5% 3/24 • Number of events 3 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	12.0% 3/25 • Number of events 3 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Nervous system disorders Headache	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	20.0% 5/25 • Number of events 5 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Skin and subcutaneous tissue disorders Hyperhidrosis	8.3% 2/24 • Number of events 2 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Cardiac disorders Palpitations	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 3 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Cardiac disorders Tachycardia paroxysmal	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Ear and labyrinth disorders Ear discomfort	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Ear and labyrinth disorders Tinnitus	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Gastrointestinal disorders Abdominal distension	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Gastrointestinal disorders Abdominal pain	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 2 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Gastrointestinal disorders Dyspepsia	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
General disorders Injection site erythema	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Infections and infestations Bronchitis	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Infections and infestations Gastroenteritis	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Infections and infestations Genital infection fungal	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Infections and infestations Oral herpes	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Infections and infestations Otitis media	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Injury, poisoning and procedural complications Arthropod sting	4.2% 1/24 • Number of events 2 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Injury, poisoning and procedural complications Procedural nausea	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Metabolism and nutrition disorders Decreased appetite	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Metabolism and nutrition disorders Food craving	4.2% 1/24 • Number of events 2 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Metabolism and nutrition disorders Hypoglycaemia	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Musculoskeletal and connective tissue disorders Back pain	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Nervous system disorders Dizziness	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	8.0% 2/25 • Number of events 3 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Reproductive system and breast disorders Balanoposthitis	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Reproductive system and breast disorders Dysmenorrhoea	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Reproductive system and breast disorders Pruritus genital	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/24 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	4.0% 1/25 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)
Skin and subcutaneous tissue disorders Rash pruritic	4.2% 1/24 • Number of events 1 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)	0.00% 0/25 • Day 1 through 28 days after the last dose of MEDI0382 (approximately 8 weeks)

Additional Information

Armando Flor

MedImmune, LLC

Phone: +1-301-398-1955

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises on going studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
• Publication restrictions are in place

Restriction type: OTHER