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

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03596177
• Collaborator: (none)
• Enrollment: 28
• Location: 1
• Arms: 2
• Actual Duration (Months): 14.9
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

An exploratory study to evaluate the effect of MEDI0382 on energy balance in overweight and obese participants with type 2 diabetes mellitus

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type II; Obesity	Drug: MEDI0382; Drug: Placebo	Phase 2

Detailed Description

An exploratory Phase 2a, randomised, double-blind, placebo-controlled study to evaluate the effect of MEDI0382 on energy balance in overweight and obese participants with type 2 diabetes mellitus

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomised, Double-Blind, Placebo-ControlledRandomised, Double-Blind, Placebo-Controlled
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An Exploratory Phase 2a, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Effect of MEDI0382 on Energy Balance in Overweight and Obese Subjects With Type 2 Diabetes Mellitus
• Actual Study Start Date: Sep 26, 2018
• Actual Primary Completion Date: Dec 22, 2019
• Actual Study Completion Date: Dec 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI0382 Participants will receive subcutaneous (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.	Drug: MEDI0382; MEDI0382 will be administered subcutaneously, 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.; Drug: Placebo; 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.
Placebo Comparator: Placebo Participants will receive 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.	Drug: Placebo; 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.

Outcome Measures

Primary Outcome Measures

1. Percent Change in Body Weight From Baseline to Day 59 [Baseline (Day 17) 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.

Secondary Outcome Measures

1. Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 [Baseline (Day 16), Day 32, and Day 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.

2. Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 [Baseline (Day 16) to Day 32 and Day 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.

3. Percent Change in Total Energy Expenditure (TEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 [Baseline (Day 15) 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.

4. Change in TEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 [Baseline (Day 15) 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.

5. Percent Change in Activity Energy Expenditure (AEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 [Baseline (Day 15) 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.

6. Change in AEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 [Baseline (Day 15) 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.

7. Percent Change in Resting Energy Expenditure (REE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 [Baseline (Day 15) 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.

8. Change in REE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 [Baseline (Day 15) 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.

9. Percent Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32 [Baseline (Day 16) 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.

10. Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32 [Baseline (Day 16) 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.

11. Change in Body Weight From Baseline to Day 59 [Baseline (Day 17) 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.

12. Percent Change in Total Body Fat Mass as Measured by Dual-energy X-ray Absorptiometry (DXA) From Baseline to Day 59 [Baseline (Day -1) 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.

13. Change in Total Body Fat Mass as Measured by DXA From Baseline to Day 59 [Baseline (Day -1) 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.

14. Percent Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59 [Baseline (Day -1) 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.

15. Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59 [Baseline (Day -1) 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.

16. Change in Fasting Glucose During a Mixed-meal Tolerance Test (MMTT) From Baseline to Day 59 [Baseline (Day -1) 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.

17. 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 [Baseline (Day -1) 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.

18. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [Day 17 through 28 days post last dose (approximately 14 months)]

    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.

19. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs [Day 17 through 28 days post last dose (approximately 14 months)]

    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.

20. Number of Participants With Abnormal Vital Signs Reported as TEAEs [Day 17 through 28 days post last dose (approximately 14 months)]

    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.

21. Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs [Day 17 through 28 days post last dose (approximately 14 months)]

    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.

22. Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 [Day 17 (predose), Day 32 (predose), Day 59; and 28 days post last dose (approximately 14 months)]

    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.

23. Percent Change in TEE as Measured by Doubly Labelled Water From Baseline (Day 17) to End of Treatment (EOT; Day 58 or 59) [Baseline (Day 17) to End of Treatment (EOT; Day 58 or 59)]

    Day 17 was considered as baseline for this outcome measure. The analysis of percent change in TEE measured by doubly labelled water is not yet complete, therefore, results of these outcomes will be reported post finalization of Clinical Study Report addendum by March 2022.

24. Change in TEE as Measured by Doubly Labelled Water From Baseline (Day 17) to End of Treatment (EOT; Day 58 or 59) [Baseline (Day 17) to End of Treatment (EOT; Day 58 or 59)]

    Day 17 was considered as baseline for this outcome measure. The analysis of change in TEE measured by doubly labelled water is not yet complete, therefore, results of these outcomes will be reported post finalization of Clinical Study Report addendum by March 2022.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participants aged >= 30 and <= 75 years at screening

2. Provision of signed and dated written informed consent (except for consent for genetic and non-genetic research and additional optional assessments) prior to any protocol-related procedures

3. Body Mass Index > 28 and <= 40 kg/m^2 at screening

4. Glycated haemoglobin (HbA1c) <= 8.0% at screening

5. Diagnosed with type 2 diabetes (T2DM) with glucose control managed with metformin, with or without a dipeptidyl peptidase 4 (DPPIV) inhibitor, Sodium-glucose co-transporter-2 inhibitors (SGLT2i), sulfonylurea, or meglitinide, where no significant dose change (increase or decrease > 50%) has occurred in the 3 months prior to screening; if the participant is on dual therapy, a 4-week washout of the non-metformin therapy (DPPIV inhibitor, SGLT2i, sulfonylurea, or meglitinide) will be required prior to Visit 4.

6. Female participants of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating.

7. Female participants of childbearing potential who are sexually active with a non-sterilised male partner must be using at least one highly effective method of contraception from screening and must agree to continue using such precautions up until 4 weeks after the last dose of study drug

Exclusion Criteria:

1. History of, or any existing condition(s) that, in the opinion of the investigator, would interfere with evaluation of the study drug, put the participant at risk, influence the participant's ability to participate or affect the interpretation of the results of the study and/or any participant unable or unwilling to follow study procedures

2. Any participant with a cardiac pacemaker or implanted/portable electronic device

3. Any participant who has received another study drug as part of a clinical study or a Glucagon-like peptide-1 (GLP-1) analogue-containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening (Visit

1. Any participant who has received any of the following medications within the specified timeframe prior to Visit 2: herbal preparations or drugs licensed for control of body weight or appetite (eg, orlistat, bupropion, naltrexone, phentermine-topiramate, phentermine, lorcaserin, opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying)

2. Concurrent participation in another study with a study drug and prior randomisation in this study is prohibited

3. Severe allergy/hypersensitivity to any of the proposed study treatments, excipients, or standardised meals

4. Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the participant has been treated with daily SC insulin within 90 days prior to screening.

5. Abnormal thyroid stimulating hormone (TSH) level of < 0.03 Milli-International Units Per Litre (mIU/L) or > 10 mIU/L confirmed on two consecutive tests

6. Regularly engage in high intensity exercise at least three times per week or have done so in the prior three months

7. Clinically significant inflammatory bowel disease, gastroparesis or other severe disease or surgery affecting the upper gastrointestinal tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data

8. Acute or chronic pancreatitis

9. Significant hepatic disease (except for nonalcoholic steatohepatitis or nonalcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results at screening:

10. Aspartate transaminase (AST) >= 3 × upper limit of normal (ULN)

11. Alanine transaminase (ALT) >= 3 × ULN

12. Total bilirubin >= 2 × ULN

13. Impaired renal function defined as estimated glomerular filtration rate (eGFR) < 45 mL/minute/1.73 m^2 at screening (GFR estimated according to the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) or the Modification of Diet in Renal Disease (MDRD) using MDRD Study Equation isotope dilution mass spectrometry-traceable [International System of Units (SI) units]

14. Poorly controlled hypertension defined as:

15. Systolic blood pressure (BP) > 180 mm Hg

16. Diastolic BP or > 100 mm Hg After 10 minutes of supine rest and confirmed by repeated measurement at screening.

Participants who fail BP screening criteria may be considered for 24-hour ambulatory BP monitoring at the discretion of the investigator. Participants who maintain a mean 24-hour BP <= 180/100 mmHg with a preserved nocturnal dip of > 15% will be considered eligible

1. Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke within 3 months prior to screening, or participants who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening

2. Severe congestive heart failure (New York Heart Association Class III or IV)

3. Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia

4. History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer

5. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody

6. Substance dependence or history of alcohol abuse and/or excess alcohol intake

7. Involvement of any AstraZeneca, Medimmune Ltd, contract research organization (CRO), or National Institute for Health Research/Wellcome Trust Cambridge Clinical Research Facility employee or their close relatives

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Cambridge		United Kingdom	CB2 0QQ

Sponsors and Collaborators

• MedImmune LLC

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 20, 2019
• Statistical Analysis Plan - Feb 23, 2019

More Information

Additional Information:

• D5670C00021 CSP redacted
• D5670C00021 SAP redacted

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT03596177
• Other Study ID Numbers: D5670C00021
• First Posted: Jul 23, 2018
• Last Update Posted: Mar 5, 2021
• Last Verified: Feb 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by MedImmune LLC: Diabetes Mellitus, Type II; Obesity; MEDI0382
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight

Study Results

Participant Flow

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Period Title: Single Blind Period
STARTED	9	19
COMPLETED	7	18
NOT COMPLETED	2	1
Period Title: Single Blind Period
STARTED	7	18
COMPLETED	7	12
NOT COMPLETED	0	6

Baseline Characteristics

Arm/Group Title	Placebo	MEDI0382	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	9	19	28
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	62.2 (7.2)	59.5 (8.4)	60.4 (8.0)
Sex: Female, Male (Count of Participants)
Female	2 22.2%	1 5.3%	3 10.7%
Male	7 77.8%	18 94.7%	25 89.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	9 100%	18 94.7%	27 96.4%
Unknown or Not Reported	0 0%	1 5.3%	1 3.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	1 5.3%	1 3.6%
Black or African American	1 11.1%	0 0%	1 3.6%
White	8 88.9%	18 94.7%	26 92.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percent Change in Body Weight From Baseline to Day 59
Description	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.
Time Frame	Baseline (Day 17) and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	14
Least Squares Mean (90% Confidence Interval) [Percent change in body weight]	-1.40	-3.98

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.58
	Confidence Interval	(2-Sided) 90%; -4.15 to -1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59
Description	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.
Time Frame	Baseline (Day 16), Day 32, and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	14
Percent change at Day 32	-5.170	-50.652
Percent change at Day 59	-10.598	-51.922

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments	Statistical Analysis for Day 32
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-45.481
	Confidence Interval	(2-Sided) 90%; -67.777 to -23.186
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments	Statistical Analysis for Day 59
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-41.323
	Confidence Interval	(2-Sided) 90%; -66.740 to -15.907
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59
Description	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.
Time Frame	Baseline (Day 16) to Day 32 and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	14
Change at Day 32	-126.271	-1677.465
Change at Day 59	-410.816	-1743.331

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments	Statistical Analysis for Day 32
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1551.194
	Confidence Interval	(2-Sided) 90%; -2190.515 to -911.873
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments	Statistical Analysis for Day 59
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1332.515
	Confidence Interval	(2-Sided) 90%; -2187.711 to -477.318
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percent Change in Total Energy Expenditure (TEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
Description	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.
Time Frame	Baseline (Day 15) and Day 58

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [Percent change in TEE]	2.032	-1.141

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.384
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.173
	Confidence Interval	(2-Sided) 90%; -9.368 to 3.022
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change in TEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
Description	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.
Time Frame	Baseline (Day 15) and Day 58

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [kilojoules/kg fat body mass]	5.969	-4.070

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.351
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-10.039
	Confidence Interval	(2-Sided) 90%; -28.287 to 8.209
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percent Change in Activity Energy Expenditure (AEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
Description	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.
Time Frame	Baseline (Day 15) and Day 58

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [Percent change in AEE]	-0.446	-0.261

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.968
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.186
	Confidence Interval	(2-Sided) 90%; -7.858 to 8.229
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change in AEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
Description	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.
Time Frame	Baseline (Day 15) and Day 58

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [kilojoules/kg fat body mass]	-1.132	-0.265

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.580
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.867
	Confidence Interval	(2-Sided) 90%; -1.810 to 3.545
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percent Change in Resting Energy Expenditure (REE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
Description	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.
Time Frame	Baseline (Day 15) and Day 58

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [Percent change in REE]	8.113	4.468

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.324
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.645
	Confidence Interval	(2-Sided) 90%; -9.894 to 2.603
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change in REE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
Description	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.
Time Frame	Baseline (Day 15) and Day 58

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [kilojoules/kg fat body mass]	13.237	7.565

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.412
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.672
	Confidence Interval	(2-Sided) 90%; -17.415 to 6.072
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percent Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32
Description	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.
Time Frame	Baseline (Day 16) and Day 32

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [Percent Change in REE]	1.189	8.546

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.177
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	7.357
	Confidence Interval	(2-Sided) 90%; -1.742 to 16.456
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32
Description	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.
Time Frame	Baseline (Day 16) and Day 32

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [kilojoules/kg fat body mass]	3.316	18.502

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.168
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	15.186
	Confidence Interval	(2-Sided) 90%; -3.151 to 33.523
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change in Body Weight From Baseline to Day 59
Description	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.
Time Frame	Baseline (Day 17) and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	14
Least Squares Mean (90% Confidence Interval) [kg]	-1.26	-3.80

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.54
	Confidence Interval	(2-Sided) 90%; -4.05 to -1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percent Change in Total Body Fat Mass as Measured by Dual-energy X-ray Absorptiometry (DXA) From Baseline to Day 59
Description	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.
Time Frame	Baseline (Day -1) and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [Percent change in total body fat mass]	-4.218	-9.340

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.107
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.122
	Confidence Interval	(2-Sided) 90%; -10.364 to 0.119
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change in Total Body Fat Mass as Measured by DXA From Baseline to Day 59
Description	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.
Time Frame	Baseline (Day -1) and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [Kg]	-1.455	-3.303

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.085
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.848
	Confidence Interval	(2-Sided) 90%; -3.605 to -0.091
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Percent Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59
Description	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.
Time Frame	Baseline (Day -1) and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [Percent change in TBFM:LM ratio]	-1.667	-4.827

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.204
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.159
	Confidence Interval	(2-Sided) 90%; -7.326 to 1.007
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59
Description	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.
Time Frame	Baseline (Day -1) and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [Ratio]	-0.010	-0.029

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.145
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.019
	Confidence Interval	(2-Sided) 90%; -0.041 to 0.003
	Parameter Dispersion	Type: Value:
	Estimation Comments

17. Secondary Outcome

Title	Change in Fasting Glucose During a Mixed-meal Tolerance Test (MMTT) From Baseline to Day 59
Description	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.
Time Frame	Baseline (Day -1) and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [mg/dL]	-12.600	-38.601

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-26.001
	Confidence Interval	(2-Sided) 90%; -37.801 to -14.201
	Parameter Dispersion	Type: Value:
	Estimation Comments

18. Secondary Outcome

Title	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
Description	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.
Time Frame	Baseline (Day -1) and Day 59

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	12
Least Squares Mean (90% Confidence Interval) [Percentage change in glucose AUC0-4hrs]	-6.773	-19.105

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, MEDI0382
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-12.332
	Confidence Interval	(2-Sided) 90%; -19.726 to -4.938
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description	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.
Time Frame	Day 17 through 28 days post last dose (approximately 14 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	18
Any TEAEs	5 55.6%	17 89.5%
Any TESAEs	0 0%	2 10.5%

20. Secondary Outcome

Title	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Description	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.
Time Frame	Day 17 through 28 days post last dose (approximately 14 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	18
Count of Participants [Participants]	0 0%	0 0%

21. Secondary Outcome

Title	Number of Participants With Abnormal Vital Signs Reported as TEAEs
Description	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.
Time Frame	Day 17 through 28 days post last dose (approximately 14 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	18
Count of Participants [Participants]	0 0%	0 0%

22. Secondary Outcome

Title	Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
Description	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.
Time Frame	Day 17 through 28 days post last dose (approximately 14 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	18
Count of Participants [Participants]	0 0%	4 21.1%

23. Secondary Outcome

Title	Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382
Description	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.
Time Frame	Day 17 (predose), Day 32 (predose), Day 59; and 28 days post last dose (approximately 14 months)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo	MEDI0382
Arm/Group Description	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.	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.
Measure Participants	7	14
ADA positive post-BL	0 0%	3 15.8%
Treatment-boosted ADA	0 0%	0 0%
Treatment-emergent ADA	0 0%	3 15.8%

24. Secondary Outcome

Title	Percent Change in TEE as Measured by Doubly Labelled Water From Baseline (Day 17) to End of Treatment (EOT; Day 58 or 59)
Description	Day 17 was considered as baseline for this outcome measure. The analysis of percent change in TEE measured by doubly labelled water is not yet complete, therefore, results of these outcomes will be reported post finalization of Clinical Study Report addendum by March 2022.
Time Frame	Baseline (Day 17) to End of Treatment (EOT; Day 58 or 59)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

25. Secondary Outcome

Title	Change in TEE as Measured by Doubly Labelled Water From Baseline (Day 17) to End of Treatment (EOT; Day 58 or 59)
Description	Day 17 was considered as baseline for this outcome measure. The analysis of change in TEE measured by doubly labelled water is not yet complete, therefore, results of these outcomes will be reported post finalization of Clinical Study Report addendum by March 2022.
Time Frame	Baseline (Day 17) to End of Treatment (EOT; Day 58 or 59)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Day 17 through 28 days post last dose (approximately 14 months)
Adverse Event Reporting Description	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.
Arm/Group Title	Placebo		MEDI0382
Arm/Group Description	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.		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.
All Cause Mortality
	Placebo		MEDI0382
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		1/18 (5.6%)
Serious Adverse Events
	Placebo		MEDI0382
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		2/18 (11.1%)
Cardiac disorders
Coronary artery thrombosis	0/7 (0%)	0	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Haematoma muscle	0/7 (0%)	0	1/18 (5.6%)	1
Other (Not Including Serious) Adverse Events
	Placebo		MEDI0382
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/7 (71.4%)		16/18 (88.9%)
Gastrointestinal disorders
Abdominal pain	1/7 (14.3%)	1	2/18 (11.1%)	2
Breath odour	0/7 (0%)	0	1/18 (5.6%)	1
Constipation	0/7 (0%)	0	3/18 (16.7%)	5
Dental caries	0/7 (0%)	0	1/18 (5.6%)	1
Diarrhoea	4/7 (57.1%)	5	3/18 (16.7%)	6
Dyspepsia	0/7 (0%)	0	1/18 (5.6%)	2
Eructation	0/7 (0%)	0	3/18 (16.7%)	3
Flatulence	0/7 (0%)	0	1/18 (5.6%)	1
Gastrooesophageal reflux disease	0/7 (0%)	0	1/18 (5.6%)	2
Nausea	2/7 (28.6%)	2	13/18 (72.2%)	19
Retching	1/7 (14.3%)	1	1/18 (5.6%)	1
Vomiting	1/7 (14.3%)	1	4/18 (22.2%)	5
General disorders
Injection site erythema	0/7 (0%)	0	2/18 (11.1%)	2
Injection site haemorrhage	0/7 (0%)	0	1/18 (5.6%)	1
Immune system disorders
Seasonal allergy	0/7 (0%)	0	1/18 (5.6%)	1
Infections and infestations
Nasopharyngitis	1/7 (14.3%)	1	0/18 (0%)	0
Tooth abscess	1/7 (14.3%)	1	0/18 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/7 (0%)	0	3/18 (16.7%)	4
Eye contusion	0/7 (0%)	0	1/18 (5.6%)	1
Skin abrasion	0/7 (0%)	0	2/18 (11.1%)	2
Investigations
Electrocardiogram t wave amplitude decreased	0/7 (0%)	0	4/18 (22.2%)	4
Metabolism and nutrition disorders
Decreased appetite	0/7 (0%)	0	5/18 (27.8%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	0/7 (0%)	0	1/18 (5.6%)	1
Back pain	1/7 (14.3%)	1	0/18 (0%)	0
Rotator cuff syndrome	0/7 (0%)	0	1/18 (5.6%)	1
Nervous system disorders
Dizziness	0/7 (0%)	0	2/18 (11.1%)	2
Headache	2/7 (28.6%)	5	2/18 (11.1%)	2
Lethargy	0/7 (0%)	0	3/18 (16.7%)	3
Restless legs syndrome	1/7 (14.3%)	1	0/18 (0%)	0
Syncope	1/7 (14.3%)	1	0/18 (0%)	0
Psychiatric disorders
Anxiety	0/7 (0%)	0	1/18 (5.6%)	1
Depressed mood	0/7 (0%)	0	1/18 (5.6%)	1
Reproductive system and breast disorders
Coital bleeding	0/7 (0%)	0	1/18 (5.6%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/7 (0%)	0	1/18 (5.6%)	1
Skin and subcutaneous tissue disorders
Blister	1/7 (14.3%)	1	0/18 (0%)	0
Vascular disorders
Hot flush	0/7 (0%)	0	1/18 (5.6%)	1

Limitations/Caveats

[Not Specified]

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