Placebo will be administered subcutaneously for 16 days in the single-blind treatment period in both MEDI0382 and placebo arms, and SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period in placebo arm.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Total of all reporting groups

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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.