Trial Outcomes & Findings for A Study to Evaluate the Effect of MEDI0382 on Energy Balance in Overweight and Obese Participants With Type 2 Diabetes Mellitus (NCT NCT03596177)

NCT ID: NCT03596177

Last Updated: 2023-01-19

Results Overview

Percent change in body weight from baseline to Day 59 is reported. Day 17 was considered as baseline for this outcome measure. The last observation carried forward (LOCF) analysis was used for missing data imputation for Day 59.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 28 participants
• Primary outcome timeframe: Baseline (Day 17) and Day 59
• Results posted on: 2023-01-19

Participant Flow

Due to COVID-19 pandemic a full analysis could not be performed due to logistical challenges and equipment failure and no further conclusions can be drawn. The results from the secondary analyses presented in this CSR Addendum do not impact any of the conclusions presented in the CSR, (Data cut off [DCO] 31 January 2020), see details in "Limitations and Caveats" section

Participant milestones

Measure	Placebo Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Single Blind Period STARTED	9	19
Single Blind Period COMPLETED	7	18
Single Blind Period NOT COMPLETED	2	1
Double Blind Period STARTED	7	18
Double Blind Period COMPLETED	7	12
Double Blind Period NOT COMPLETED	0	6

Reasons for withdrawal

Measure	Placebo Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Single Blind Period Withdrawal by Subject	1	1
Single Blind Period Other	1	0
Double Blind Period Withdrawal by Subject	0	1
Double Blind Period Other	0	4
Double Blind Period Death during safety follow-up	0	1

Baseline Characteristics

A Study to Evaluate the Effect of MEDI0382 on Energy Balance in Overweight and Obese Participants With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Placebo n=9 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=19 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.	Total n=28 Participants Total of all reporting groups
Age, Continuous	62.2 Years STANDARD_DEVIATION 7.2 • n=5 Participants	59.5 Years STANDARD_DEVIATION 8.4 • n=7 Participants	60.4 Years STANDARD_DEVIATION 8.0 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	18 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	18 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 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	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	18 Participants n=7 Participants	26 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: Baseline (Day 17) and Day 59

Population: Modified intent-to-treat (ITT) population: Participants in ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 59.

Percent change in body weight from baseline to Day 59 is reported. Day 17 was considered as baseline for this outcome measure. The last observation carried forward (LOCF) analysis was used for missing data imputation for Day 59.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=14 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Percent Change in Body Weight From Baseline to Day 59	-1.40 Percent change in body weight Interval -2.66 to -0.13	-3.98 Percent change in body weight Interval -4.85 to -3.1

SECONDARY outcome

Timeframe: Baseline (Day 16), Day 32, and Day 59

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Days 32 and 59.

Total energy intake in kilojoules (kJ) were recorded in a food diary after ad libitum lunch on Days 16, 32, and 59. The ad libitum lunch was a standardised solid meal with food of known macronutrient content. Participants were advised to eat freely until they feel comfortably full and the meal duration was flexible according to participant's preference. During the meal, the quantity of food ingested was recorded by study site staff without participants' awareness that food consumption was recorded. Percent change in total energy intake from the ad libitum lunch is reported. Day 16 was considered as baseline for this outcome measure. The LOCF analysis was used for missing data imputation for Day 59.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=14 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 Percent change at Day 32	-5.170 Percent change in total energy intake Interval -23.344 to 13.003	-50.652 Percent change in total energy intake Interval -63.48 to -37.823
Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 Percent change at Day 59	-10.598 Percent change in total energy intake Interval -31.316 to 10.119	-51.922 Percent change in total energy intake Interval -66.546 to -37.297

SECONDARY outcome

Timeframe: Baseline (Day 16) to Day 32 and Day 59

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Days 32 and 59.

Total energy intake in kilojoules (kJ) were recorded in a food diary after ad libitum lunch on Days 16, 32, and 59. The ad libitum lunch was a standardised solid meal with food of known macronutrient content. Participants were advised to eat freely until they feel comfortably full and the meal duration was flexible according to participant's preference. During the meal, the quantity of food ingested was recorded by study site staff without participants' awareness that food consumption was recorded. Change in total energy intake from the ad libitum lunch is reported. Day 16 was considered as baseline for this outcome measure. The LOCF analysis was used for missing data imputation for Day 59.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=14 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 Change at Day 32	-126.271 Kilojoules Interval -647.387 to 394.846	-1677.465 Kilojoules Interval -2045.322 to -1309.607
Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 Change at Day 59	-410.816 Kilojoules Interval -1107.896 to 286.263	-1743.331 Kilojoules Interval -2235.4 to -1251.261

SECONDARY outcome

Timeframe: Baseline (Day 15) and Day 58

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 58.

A whole room calorimetry assessment was used to measure gaseous exchange while exercising and therefore indirect estimates of energy expenditure over a 24-hour period. For assessment, participants had to enter the whole room calorimeter for up to 36 hours and reside inside for this entire duration (include toilet visits). During the time in the calorimeter participants were asked to exercise on an exercise bike for 15-minute intervals at 4 times. During these sessions participants were asked to aim for a heart rate of 65% of maximum (defined as 220 beats per minute minus age) and complete the full 15-minute session. In addition, participants abstained from caffeinated drinks for at least 24 hours prior to measurements as caffeine may increase energy expenditure (EE) and dietary advice was given to ensure participants had a neutral energy balance prior to whole calorimetry assessments. Percent change in TEE is reported. Day 15 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Percent Change in Total Energy Expenditure (TEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58	2.032 Percent change in TEE Interval -2.833 to 6.898	-1.141 Percent change in TEE Interval -4.825 to 2.544

SECONDARY outcome

Timeframe: Baseline (Day 15) and Day 58

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 58.

A whole room calorimetry assessment was used to measure gaseous exchange while exercising and therefore indirect estimates of energy expenditure over a 24-hour period. For the assessment, participants had to enter the whole room calorimeter for up to 36 hours and reside inside for this entire duration (this will include toilet visits too). During the time in the calorimeter participants were asked to exercise on an exercise bike for 15-minute intervals at 4 times. During these sessions participants were asked to aim for a heart rate of 65% of maximum (defined as 220 beats per minute minus age) and complete the full 15-minute session. In addition, participants abstained from caffeinated drinks for at least 24 hours prior to measurements as caffeine may increase EE and dietary advice was given to ensure participants had a neutral energy balance prior to whole calorimetry assessments. Change in TEE is reported. Day 15 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Change in TEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58	5.969 kilojoules/kg fat body mass Interval -8.364 to 20.302	-4.070 kilojoules/kg fat body mass Interval -14.924 to 6.783

SECONDARY outcome

Timeframe: Baseline (Day 15) and Day 58

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 58.

A whole room calorimetry assessment was used to measure gaseous exchange while exercising and therefore indirect estimates of energy expenditure over a 24-hour period. For the assessment, participants had to enter the whole room calorimeter for up to 36 hours and reside inside for this entire duration (this will include toilet visits too). During the time in the calorimeter participants were asked to exercise on an exercise bike for 15-minute intervals at 4 times. During these sessions participants were asked to aim for a heart rate of 65% of maximum (defined as 220 beats per minute minus age) and complete the full 15-minute session. In addition, participants abstained from caffeinated drinks for at least 24 hours prior to measurements as caffeine may increase EE and dietary advice was given to ensure participants had a neutral energy balance prior to whole calorimetry assessments. Percent change in AEE is reported. Day 15 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Percent Change in Activity Energy Expenditure (AEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58	-0.446 Percent change in AEE Interval -6.836 to 5.943	-0.261 Percent change in AEE Interval -5.139 to 4.618

SECONDARY outcome

Timeframe: Baseline (Day 15) and Day 58

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 58.

A whole room calorimetry assessment was used to measure gaseous exchange while exercising and therefore indirect estimates of energy expenditure over a 24-hour period. For the assessment, participants had to enter the whole room calorimeter for up to 36 hours and reside inside for this entire duration (this will include toilet visits too). During the time in the calorimeter participants were asked to exercise on an exercise bike for 15-minute intervals at 4 times. During these sessions participants were asked to aim for a heart rate of 65% of maximum (defined as 220 beats per minute minus age) and complete the full 15-minute session. In addition, participants abstained from caffeinated drinks for at least 24 hours prior to measurements as caffeine may increase EE and dietary advice was given to ensure participants had a neutral energy balance prior to whole calorimetry assessments. Change in AEE is reported. Day 15 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Change in AEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58	-1.132 kilojoules/kg fat body mass Interval -3.259 to 0.995	-0.265 kilojoules/kg fat body mass Interval -1.889 to 1.359

SECONDARY outcome

Timeframe: Baseline (Day 15) and Day 58

Population: mITT population:Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 58.

The REE represents the amount of calories required for a 24-hour period by the body during a non-active period and is assessed by whole room indirect calorimetry method. Percent change in REE is reported. Day 15 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Percent Change in Resting Energy Expenditure (REE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58	8.113 Percent change in REE Interval 3.254 to 12.972	4.468 Percent change in REE Interval 0.816 to 8.12

SECONDARY outcome

Timeframe: Baseline (Day 15) and Day 58

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 58.

The REE represents the amount of calories required for a 24-hour period by the body during a non-active period and is assessed by whole room indirect calorimetry method. Change in REE is reported. Day 15 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Change in REE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58	13.237 kilojoules/kg fat body mass Interval 4.104 to 22.369	7.565 kilojoules/kg fat body mass Interval 0.701 to 14.429

SECONDARY outcome

Timeframe: Baseline (Day 16) and Day 32

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 32.

Hood calorimetry assessment was used to measure REE. A large plastic hood is placed over participants head for 20 minutes and measurements of gaseous exchange are undertaken. Participants were rested for at least 1 hour prior to hood calorimetry measures; during a hood calorimetry assessment the participants were asked to remain quiet and rested for 40 minutes in total with 10 minutes before and after the assessment to allow for room air assessment. Percent change in REE is reported. Day 16 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Percent Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32	1.189 Percent Change in REE Interval -5.955 to 8.332	8.546 Percent Change in REE Interval 3.138 to 13.954

SECONDARY outcome

Timeframe: Baseline (Day 16) and Day 32

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 32.

Hood calorimetry assessment was used to measure REE. A large plastic hood is placed over participants head for 20 minutes and measurements of gaseous exchange are undertaken. Participants were rested for at least 1 hour prior to hood calorimetry measures; during a hood calorimetry assessment the participants were asked to remain quiet and rested for 40 minutes in total with 10 minutes before and after the assessment to allow for room air assessment. Change in REE is reported. Day 16 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32	3.316 kilojoules/kg fat body mass Interval -11.08 to 17.712	18.502 kilojoules/kg fat body mass Interval 7.604 to 29.4

SECONDARY outcome

Timeframe: Baseline (Day 17) and Day 59

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 59.

Change in body weight from baseline to Day 59 is reported. Day 17 was considered as baseline for this outcome measure. The LOCF analysis was used for missing data imputation for Day 59.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=14 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Change in Body Weight From Baseline to Day 59	-1.26 kg Interval -2.48 to -0.05	-3.80 kg Interval -4.65 to -2.96

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 59

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 59.

The total body fat mass was measured in kilograms (kg) using DXA. Participants body was scanned using DXA scanner and total body fat mass was determined. Percent change in total body fat mass is reported. Day -1 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Percent Change in Total Body Fat Mass as Measured by Dual-energy X-ray Absorptiometry (DXA) From Baseline to Day 59	-4.218 Percent change in total body fat mass Interval -8.249 to -0.186	-9.340 Percent change in total body fat mass Interval -12.343 to -6.337

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 59

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 59.

The total body fat mass was measured in kg using DXA. Participants body was scanned using DXA scanner and total body fat mass was determined. Change in total body fat mass is reported. Day -1 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Change in Total Body Fat Mass as Measured by DXA From Baseline to Day 59	-1.455 Kg Interval -2.806 to -0.103	-3.303 Kg Interval -4.31 to -2.296

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 59

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 59.

The total body fat mass and lean body mass was measured in kg using DXA. Participants body was scanned using DXA scanner and total body fat mass and lean mass was determined. Percent change in total body fat mass:lean mass (TBFM:LM) ratio is reported. Day -1 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Percent Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59	-1.667 Percent change in TBFM:LM ratio Interval -4.934 to 1.6	-4.827 Percent change in TBFM:LM ratio Interval -7.298 to -2.355

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 59

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 59.

The total body fat mass and lean body mass was measured in kg using DXA. Participants body was scanned using DXA scanner and total body fat mass and lean mass was determined. Change in total body fat mass:lean mass (TBFM:LM) ratio is reported. Day -1 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59	-0.010 Ratio Interval -0.027 to 0.007	-0.029 Ratio Interval -0.042 to -0.016

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 59

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 59.

The MMTT involves consumption of a standardized solid breakfast meal within 5 minutes, following a minimum 12 hours fast, and timed serial blood samples are obtained for measurement of glucose levels through 240 minutes with no additional food intake during this time. Change in fasting glucose is reported. Day -1 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Change in Fasting Glucose During a Mixed-meal Tolerance Test (MMTT) From Baseline to Day 59	-12.600 mg/dL Interval -21.673 to -3.527	-38.601 mg/dL Interval -45.36 to -31.842

SECONDARY outcome

Timeframe: Baseline (Day -1) and Day 59

Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, "number of participants analyzed" denotes those participants who were evaluable at baseline and Day 59.

The MMTT involves consumption of a standardized solid breakfast meal within 5 minutes, following a minimum 12 hours fast, and timed serial blood samples are obtained for measurement of glucose levels through 240 minutes with no additional food intake during this time. Percent change in glucose AUC0-4hrs during MMTT is reported. Day -1 was considered as baseline for this outcome measure.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=12 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Percent Change in Glucose Area Under the Concentration-time Curve at 0 to 4 Hours (AUC0-4hrs) During a MMTT From Baseline to Day 59	-6.773 Percentage change in glucose AUC0-4hrs Interval -12.528 to -1.018	-19.105 Percentage change in glucose AUC0-4hrs Interval -23.434 to -14.777

SECONDARY outcome

Timeframe: Day 17 through 28 days post last dose (approximately 14 months)

Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they 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, and congenital anomaly. 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. From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=18 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TEAEs	5 Participants	17 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Any TESAEs	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Day 17 through 28 days post last dose (approximately 14 months)

Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they received.

Number of participants with clinical laboratory abnormalities reported as TEAEs are reported. Clinical laboratory abnormalities are defined as any abnormal findings in analysis of serum chemistry, hematology, and urinalysis. From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=18 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 17 through 28 days post last dose (approximately 14 months)

Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they received.

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs reported as TEAEs included any abnormal findings in body temperature, blood pressure, pulse rate, and respiratory rate. From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=18 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Number of Participants With Abnormal Vital Signs Reported as TEAEs	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 17 through 28 days post last dose (approximately 14 months)

Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they received.

Number of participants with abnormal ECG reported as TEAEs are reported. From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=18 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs	0 Participants	4 Participants

SECONDARY outcome

Timeframe: Day 17 (predose), Day 32 (predose), Day 59; and 28 days post last dose (approximately 14 months)

Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they received. Here, "number of participants analyzed" denotes those participants who had post-baseline ADA results.

Number of participants with positive ADA to MEDI0382 are reported. Treatment-boosted ADA is defined as baseline ADA titer that was boosted to a 4-fold or higher level following drug administration. Treatment-emergent ADA is defined as the sum of treatment-induced ADA (post-baseline positive only) and treatment-boosted ADA. From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, ADA were not applicable for Day 1 to Day 16. The ADAs were recorded and reported for double-blind treatment period ie, from Day 17.

Outcome measures

Measure	Placebo n=7 Participants Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=14 Participants Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 ADA positive post-BL	0 Participants	3 Participants
Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 Treatment-boosted ADA	0 Participants	0 Participants
Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 Treatment-emergent ADA	0 Participants	3 Participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

MEDI0382

Serious events: 2 serious events

Other events: 16 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo n=7 participants at risk Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=18 participants at risk Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Cardiac disorders Coronary artery thrombosis	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Musculoskeletal and connective tissue disorders Haematoma muscle	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.

Other adverse events

Measure	Placebo n=7 participants at risk Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.	MEDI0382 n=18 participants at risk Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Gastrointestinal disorders Flatulence	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 2 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Abdominal pain	14.3% 1/7 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	11.1% 2/18 • Number of events 2 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Breath odour	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Constipation	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	16.7% 3/18 • Number of events 5 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Dental caries	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Diarrhoea	57.1% 4/7 • Number of events 5 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	16.7% 3/18 • Number of events 6 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Dyspepsia	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 2 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Eructation	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	16.7% 3/18 • Number of events 3 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Nausea	28.6% 2/7 • Number of events 2 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	72.2% 13/18 • Number of events 19 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Retching	14.3% 1/7 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Gastrointestinal disorders Vomiting	14.3% 1/7 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	22.2% 4/18 • Number of events 5 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
General disorders Injection site erythema	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	11.1% 2/18 • Number of events 2 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
General disorders Injection site haemorrhage	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Immune system disorders Seasonal allergy	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Infections and infestations Nasopharyngitis	14.3% 1/7 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	0.00% 0/18 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Infections and infestations Tooth abscess	14.3% 1/7 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	0.00% 0/18 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Injury, poisoning and procedural complications Contusion	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	16.7% 3/18 • Number of events 4 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Injury, poisoning and procedural complications Eye contusion	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	11.1% 2/18 • Number of events 2 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Investigations Electrocardiogram t wave amplitude decreased	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	22.2% 4/18 • Number of events 4 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	27.8% 5/18 • Number of events 5 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Musculoskeletal and connective tissue disorders Back pain	14.3% 1/7 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	0.00% 0/18 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Nervous system disorders Dizziness	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	11.1% 2/18 • Number of events 2 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Nervous system disorders Headache	28.6% 2/7 • Number of events 5 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	11.1% 2/18 • Number of events 2 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Nervous system disorders Lethargy	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	16.7% 3/18 • Number of events 3 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Nervous system disorders Restless legs syndrome	14.3% 1/7 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	0.00% 0/18 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Nervous system disorders Syncope	14.3% 1/7 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	0.00% 0/18 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Psychiatric disorders Anxiety	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Psychiatric disorders Depressed mood	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Reproductive system and breast disorders Coital bleeding	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Skin and subcutaneous tissue disorders Blister	14.3% 1/7 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	0.00% 0/18 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.
Vascular disorders Hot flush	0.00% 0/7 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.	5.6% 1/18 • Number of events 1 • Day 17 through 28 days post last dose (approximately 14 months) From Day 1 to Day 16 all participants in both treatment arms received placebo so that analysis of energy intake in participants who were randomised to MEDI0382 may be performed. Hence, TEAEs were not applicable for Day 1 to Day 16. The TEAEs were recorded and reported for double-blind treatment period ie, from Day 17.

Additional Information

Victoria Parker

MedImmune, LLC

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Email: information.center@astrazeneca.com

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