Diabetes Mellitus, Type II, Obesity
Conditions
Keywords
Diabetes Mellitus, Type II, Obesity, MEDI0382
Brief summary
An exploratory study to evaluate the effect of MEDI0382 on energy balance in overweight and obese participants with type 2 diabetes mellitus
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
Interventions
DRUGMEDI0382
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.
DRUGPlacebo
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.
Sponsors
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomised, Double-Blind, Placebo-Controlled
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
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) 4. 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) 5. Concurrent participation in another study with a study drug and prior randomisation in this study is prohibited 6. Severe allergy/hypersensitivity to any of the proposed study treatments, excipients, or standardised meals 7. 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. 8. 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 9. Regularly engage in high intensity exercise at least three times per week or have done so in the prior three months 10. 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 11. Acute or chronic pancreatitis 12. 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: 1. Aspartate transaminase (AST) \>= 3 × upper limit of normal (ULN) 2. Alanine transaminase (ALT) \>= 3 × ULN 3. 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: 1. Systolic blood pressure (BP) \> 180 mm Hg 2. 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 15. 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 16. Severe congestive heart failure (New York Heart Association Class III or IV) 17. Basal calcitonin level \> 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia 18. 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 19. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody 20. Substance dependence or history of alcohol abuse and/or excess alcohol intake 21. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United Kingdom
Participant flow
Pre-assignment details
Due to COVID-19 pandemic a full analysis could not be performed due to logistical challenges and equipment failure and no further conclusions can be drawn. The results from the secondary analyses presented in this CSR Addendum do not impact any of the conclusions presented in the CSR, (Data cut off \[DCO\] 31 January 2020), see details in Limitations and Caveats section
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period. | 9 |
| MEDI0382 Participants received SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period. | 19 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double Blind Period | Death during safety follow-up | 0 | 1 |
| Double Blind Period | Other | 0 | 4 |
| Double Blind Period | Withdrawal by Subject | 0 | 1 |
| Single Blind Period | Other | 1 | 0 |
| Single Blind Period | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | MEDI0382 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 59.5 Years STANDARD_DEVIATION 8.4 | 60.4 Years STANDARD_DEVIATION 8 | 62.2 Years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 27 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 18 Participants | 26 Participants | 8 Participants |
| Sex: Female, Male Female | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 18 Participants | 25 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 1 / 18 |
| other Total, other adverse events | 5 / 7 | 16 / 18 |
| serious Total, serious adverse events | 0 / 7 | 2 / 18 |
Outcome results
Primary
Percent Change in Body Weight From Baseline to 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.
Time frame: Baseline (Day 17) and Day 59
Population: Modified intent-to-treat (ITT) population: Participants in ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 59.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change in Body Weight From Baseline to Day 59 | -1.40 Percent change in body weight |
| MEDI0382 | Percent Change in Body Weight From Baseline to Day 59 | -3.98 Percent change in body weight |
p-value: 0.01190% CI: [-4.15, -1]ANCOVA
Secondary
Change in AEE as Measured by Whole Room Indirect Calorimetry From Baseline to 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.
Time frame: Baseline (Day 15) and Day 58
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 58.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in AEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | -1.132 kilojoules/kg fat body mass |
| MEDI0382 | Change in AEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | -0.265 kilojoules/kg fat body mass |
p-value: 0.5890% CI: [-1.81, 3.545]ANCOVA
Secondary
Change in Body Weight From Baseline to 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.
Time frame: Baseline (Day 17) and Day 59
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 59.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in Body Weight From Baseline to Day 59 | -1.26 kg |
| MEDI0382 | Change in Body Weight From Baseline to Day 59 | -3.80 kg |
p-value: 0.00990% CI: [-4.05, -1.03]ANCOVA
Secondary
Change in Fasting Glucose During a Mixed-meal Tolerance Test (MMTT) From Baseline to 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.
Time frame: Baseline (Day -1) and Day 59
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 59.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in Fasting Glucose During a Mixed-meal Tolerance Test (MMTT) From Baseline to Day 59 | -12.600 mg/dL |
| MEDI0382 | Change in Fasting Glucose During a Mixed-meal Tolerance Test (MMTT) From Baseline to Day 59 | -38.601 mg/dL |
p-value: 0.00190% CI: [-37.801, -14.201]ANCOVA
Secondary
Change in REE as Measured by Hood Indirect Calorimetry From Baseline to 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.
Time frame: Baseline (Day 16) and Day 32
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 32.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32 | 3.316 kilojoules/kg fat body mass |
| MEDI0382 | Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32 | 18.502 kilojoules/kg fat body mass |
p-value: 0.16890% CI: [-3.151, 33.523]ANCOVA
Secondary
Change in REE as Measured by Whole Room Indirect Calorimetry From Baseline to 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.
Time frame: Baseline (Day 15) and Day 58
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 58.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in REE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | 13.237 kilojoules/kg fat body mass |
| MEDI0382 | Change in REE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | 7.565 kilojoules/kg fat body mass |
p-value: 0.41290% CI: [-17.415, 6.072]ANCOVA
Secondary
Change in TEE as Measured by Whole Room Indirect Calorimetry From Baseline to 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.
Time frame: Baseline (Day 15) and Day 58
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 58.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in TEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | 5.969 kilojoules/kg fat body mass |
| MEDI0382 | Change in TEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | -4.070 kilojoules/kg fat body mass |
p-value: 0.35190% CI: [-28.287, 8.209]ANCOVA
Secondary
Change in Total Body Fat Mass as Measured by DXA From Baseline to 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.
Time frame: Baseline (Day -1) and Day 59
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 59.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in Total Body Fat Mass as Measured by DXA From Baseline to Day 59 | -1.455 Kg |
| MEDI0382 | Change in Total Body Fat Mass as Measured by DXA From Baseline to Day 59 | -3.303 Kg |
p-value: 0.08590% CI: [-3.605, -0.091]ANCOVA
Secondary
Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to 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.
Time frame: Baseline (Day -1) and Day 59
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 59.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59 | -0.010 Ratio |
| MEDI0382 | Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59 | -0.029 Ratio |
p-value: 0.14590% CI: [-0.041, 0.003]ANCOVA
Secondary
Change in Total Energy Intake From the ad Libitum Lunch From Baseline 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.
Time frame: Baseline (Day 16) to Day 32 and Day 59
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Days 32 and 59.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 | Change at Day 32 | -126.271 Kilojoules |
| Placebo | Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 | Change at Day 59 | -410.816 Kilojoules |
| MEDI0382 | Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 | Change at Day 32 | -1677.465 Kilojoules |
| MEDI0382 | Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 | Change at Day 59 | -1743.331 Kilojoules |
Comparison: Statistical Analysis for Day 32p-value: <0.00190% CI: [-2190.515, -911.873]ANCOVA
Comparison: Statistical Analysis for Day 59p-value: 0.01590% CI: [-2187.711, -477.318]ANCOVA
Secondary
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
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)
Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | 0 Participants |
| MEDI0382 | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs | 0 Participants |
Secondary
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
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)
Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs | 0 Participants |
| MEDI0382 | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs | 4 Participants |
Secondary
Number of Participants With Abnormal Vital Signs Reported as TEAEs
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)
Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Abnormal Vital Signs Reported as TEAEs | 0 Participants |
| MEDI0382 | Number of Participants With Abnormal Vital Signs Reported as TEAEs | 0 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382
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)
Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they received. Here, number of participants analyzed denotes those participants who had post-baseline ADA results.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 | ADA positive post-BL | 0 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 | Treatment-boosted ADA | 0 Participants |
| Placebo | Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 | Treatment-emergent ADA | 0 Participants |
| MEDI0382 | Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 | ADA positive post-BL | 3 Participants |
| MEDI0382 | Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 | Treatment-boosted ADA | 0 Participants |
| MEDI0382 | Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382 | Treatment-emergent ADA | 3 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
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)
Population: Participants who received any study drug in the double-blind treatment period and were analyzed according to the treatment they received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAEs | 5 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAEs | 0 Participants |
| MEDI0382 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TEAEs | 17 Participants |
| MEDI0382 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | Any TESAEs | 2 Participants |
Secondary
Percent Change in Activity Energy Expenditure (AEE) as Measured by Whole Room Indirect Calorimetry From Baseline to 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.
Time frame: Baseline (Day 15) and Day 58
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 58.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change in Activity Energy Expenditure (AEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | -0.446 Percent change in AEE |
| MEDI0382 | Percent Change in Activity Energy Expenditure (AEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | -0.261 Percent change in AEE |
p-value: 0.96890% CI: [-7.858, 8.229]ANCOVA
Secondary
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
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
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 59.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change in Glucose Area Under the Concentration-time Curve at 0 to 4 Hours (AUC0-4hrs) During a MMTT From Baseline to Day 59 | -6.773 Percentage change in glucose AUC0-4hrs |
| MEDI0382 | 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 | -19.105 Percentage change in glucose AUC0-4hrs |
p-value: 0.0190% CI: [-19.726, -4.938]ANCOVA
Secondary
Percent Change in REE as Measured by Hood Indirect Calorimetry From Baseline to 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.
Time frame: Baseline (Day 16) and Day 32
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 32.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32 | 1.189 Percent Change in REE |
| MEDI0382 | Percent Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32 | 8.546 Percent Change in REE |
p-value: 0.17790% CI: [-1.742, 16.456]ANCOVA
Secondary
Percent Change in Resting Energy Expenditure (REE) as Measured by Whole Room Indirect Calorimetry From Baseline to 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.
Time frame: Baseline (Day 15) and Day 58
Population: mITT population:Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 58.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change in Resting Energy Expenditure (REE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | 8.113 Percent change in REE |
| MEDI0382 | Percent Change in Resting Energy Expenditure (REE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | 4.468 Percent change in REE |
p-value: 0.32490% CI: [-9.894, 2.603]ANCOVA
Secondary
Percent Change in Total Body Fat Mass as Measured by Dual-energy X-ray Absorptiometry (DXA) From Baseline to 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.
Time frame: Baseline (Day -1) and Day 59
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 59.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change in Total Body Fat Mass as Measured by Dual-energy X-ray Absorptiometry (DXA) From Baseline to Day 59 | -4.218 Percent change in total body fat mass |
| MEDI0382 | Percent Change in Total Body Fat Mass as Measured by Dual-energy X-ray Absorptiometry (DXA) From Baseline to Day 59 | -9.340 Percent change in total body fat mass |
p-value: 0.10790% CI: [-10.364, 0.119]ANCOVA
Secondary
Percent Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to 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.
Time frame: Baseline (Day -1) and Day 59
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 59.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59 | -1.667 Percent change in TBFM:LM ratio |
| MEDI0382 | Percent Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59 | -4.827 Percent change in TBFM:LM ratio |
p-value: 0.20490% CI: [-7.326, 1.007]ANCOVA
Secondary
Percent Change in Total Energy Expenditure (TEE) as Measured by Whole Room Indirect Calorimetry From Baseline to 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.
Time frame: Baseline (Day 15) and Day 58
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Day 58.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change in Total Energy Expenditure (TEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | 2.032 Percent change in TEE |
| MEDI0382 | Percent Change in Total Energy Expenditure (TEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58 | -1.141 Percent change in TEE |
p-value: 0.38490% CI: [-9.368, 3.022]ANCOVA
Secondary
Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline 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. 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
Population: mITT population: Participants in the ITT population (who received any study drug) who received at least one dose of the study drug in the double-blind treatment period, and analyzed according to their randomized treatment group. Here, number of participants analyzed denotes those participants who were evaluable at baseline and Days 32 and 59.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 | Percent change at Day 32 | -5.170 Percent change in total energy intake |
| Placebo | Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 | Percent change at Day 59 | -10.598 Percent change in total energy intake |
| MEDI0382 | Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 | Percent change at Day 32 | -50.652 Percent change in total energy intake |
| MEDI0382 | Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59 | Percent change at Day 59 | -51.922 Percent change in total energy intake |
Comparison: Statistical Analysis for Day 32p-value: 0.00290% CI: [-67.777, -23.186]ANCOVA
Comparison: Statistical Analysis for Day 59p-value: 0.01190% CI: [-66.74, -15.907]ANCOVA