A Study to Evaluate the Safety and Tolerability of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period

Time frame · Baseline (Day -1) through Day 56 (end of Up-titration period)

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.

Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period

Time frame · Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A 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.

Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period

Time frame · Baseline (Day -1) through Day 56 (end of Up-titration period)

Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.

Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period

Time frame · Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG.

Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period

Time frame · Baseline (Day -1) through Day 56 (end of Up-titration period)

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).

Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period

Time frame · Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate).

Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period

Time frame · Baseline (Day -1) through Day 56 (end of Up-titration period)

Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and, endocrine.

Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period

Time frame · Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examination findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and endocrine.

Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382

Time frame · Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 is reported.

Maximum Observed Serum Concentration (Cmax) of MEDI0382

Time frame · Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

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

Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382

Time frame · Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

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

Trough Plasma Concentration (Ctrough) of MEDI0382

Time frame · Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration (Ctrough) of MEDI0382 is reported.

Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC

Time frame · Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84

The Ro was calculated using the AUC method which account for the overall exposure measured using the Day 1 and specified time point (Day I). Ro = AUCtrough \[Day I\]/AUCtrough \[Day 1\]; where I is the specified day.

Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment

Time frame · Pre-dose (Day -2), Days 7, 14, 35, 42, 56; Day 21 of 3 week treatment extension, and 28 days post last dose (approximately 5 months)

Number of participants with positive ADA to MEDI0382 are reported.

Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM)

Time frame · Baseline (Day -1) through Day 56 (end of the up-titration period), Day 77 (end of the treatment extension period) and Day 91 (end of the follow-up period)

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. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. During 14 days follow-up (Day 91), last observation carried forward (LOCF) approach was used to calculate the value.

Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM

Time frame · Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period

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. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level.

Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM

Time frame · Baseline (Day -1) through Day 7 (end of Week 1), Day 56 (end of the up-titration period), and Day 77 (end of the treatment extension period)

Change from baseline in percentage of glucose AUC4Hrs during a standardized breakfast, lunch, and evening meal over time is reported. 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. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level.

Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM

Time frame · Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period

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. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Change from baseline in coefficient of variation in glucose over 7 days is reported.