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This is a Phase 2a, randomized, blinded, placebo-controlled study in up to 20 overweight or obese participants with type 2 diabetes mellitus. The participants will participate in the study for approximately 18 weeks, including screening, run-in and treatment periods and a safety follow-up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MEDI0382 Cohort 1 | Experimental | Participants will receive subcutaneous (SC) dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week treatment extension period (TEP). |
|
| Placebo Cohort 1 | Placebo Comparator | Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the uptitration period and thereafter once daily through 3 week TEP. |
|
| MEDI0382 Cohort 2 | Experimental | Participants will receive SC dose of MEDI0382 uptitrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP. |
|
| Placebo Cohort 2 | Placebo Comparator | Participants will receive SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MEDI0382 | Drug | Subcutaneous dose of MEDI0382 will be up-titrated weekly once daily up to 8 weeks during the uptitration period and thereafter once daily in 3-week TEP. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. | Baseline (Day -1) through Day 56 (end of Up-titration period) |
| Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. | Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
| Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period | Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG. | Baseline (Day -1) through Day 56 (end of Up-titration period) |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 | Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 is reported. | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
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Inclusion Criteria:
Exclusion Criteria:
History of, or any existing condition 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 during the run-in period.
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.
Concurrent participation in another study of any kind and repeat randomization in this study is prohibited.
Any participant who has received any of the following medications prior to the start of the study:
Severe allergy/hypersensitivity to any of the proposed study treatments, standardized meals, or excipients.
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.
Acute pancreatitis, pancreatic amylase, and/or pancreatic lipase > 3 × upper limit of normal range (ULN); history of chronic pancreatitis; or serum triglyceride levels > 11 mmol/L (1000 mg/dL) at screening.
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.
Significant hepatic disease (except for nonalcoholic steatohepatitis (NASH) or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results at screening:
Impaired renal function defined as estimated glomerular filtration rate (GFR) < 60 mL/minute/1.73m^2 at screening.
Poorly controlled hypertension defined as:
Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead ECG or any abnormalities that may interfere with the interpretation of serial ECG changes.
Prolonged QT intervals corrected for heart rate or family history of long QT-segment at screening.
PR (PQ) interval prolongation, intermittent second or third-degree atrioventricular (AV) block, or AV dissociation.
Persistent or intermittent complete bundle branch block.
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.
Severe congestive heart failure.
Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia.
Hemoglobinopathy, hemolytic anemia or chronic anemia or any other condition known to interfere with the interpretation of HbA1c measurement.
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.
Any positive results for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
History of substance dependence, alcohol abuse, or excessive alcohol intake. Participants who use benzodiazepines for chronic anxiety or sleep disorders may be permitted to enter the study.
Symptoms of depression or any other psychiatric disorder requiring treatment with medication.
History of severe allergy/hypersensitivity, including to any component of the investigational product formulation or other biological agent, or ongoing clinically important allergy/hypersensitivity.
Blood/plasma donation within 1 month of screening.
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| Name | Affiliation | Role |
|---|---|---|
| Tim Heise, MD | Profil Institut für Stoffwechselforschung GmbH | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Neuss | 41460 | Germany |
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| Label | URL |
|---|---|
| CSP redacted protocol | View source |
| SAP redacted | View source |
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A total of 20 participants were randomized to the study.
The study was conducted in Germany between 07Jan2019 and 28May2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo Cohort 1 | Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP). |
| FG001 | MEDI0382 Cohort 1 | Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP. |
| FG002 | Placebo Cohort 2 | Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP. |
| FG003 | MEDI0382 Cohort 2 | Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo Cohort 1 | Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP). |
| BG001 | MEDI0382 Cohort 1 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day -1) through Day 56 (end of Up-titration period) |
|
Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo Cohort 1 | Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Lars Hansen | MedImmune, LLC | +1 301 398 4563 | information.center@astrazeneca.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 16, 2019 | May 20, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 22, 2019 | May 20, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| D003920 | Diabetes Mellitus |
| D009765 | Obesity |
| D050177 | Overweight |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C000624433 | cotadutide |
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| Placebo | Drug | Subcutaneous dose of placebo matched to MEDI0382 will be administered once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP. |
|
| Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period |
Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG. |
| Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period | Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). | Baseline (Day -1) through Day 56 (end of Up-titration period) |
| Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period | Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). | Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
| Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period | Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and, endocrine. | Baseline (Day -1) through Day 56 (end of Up-titration period) |
| Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period | Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examination findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and endocrine. | Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine. | Baseline (Day -1) through Day 56 (end of Up-titration period) |
| Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine. | Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
| Maximum Observed Serum Concentration (Cmax) of MEDI0382 | Maximum observed serum concentration (Cmax) of MEDI0382 is reported. | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
| Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 | Time to observed maximum serum concentration (Tmax) of MEDI0382 is reported. | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
| Trough Plasma Concentration (Ctrough) of MEDI0382 | Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration (Ctrough) of MEDI0382 is reported. | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
| Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC | The Ro was calculated using the AUC method which account for the overall exposure measured using the Day 1 and specified time point (Day I). Ro = AUCtrough [Day I]/AUCtrough [Day 1]; where I is the specified day. | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
| Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment | Number of participants with positive ADA to MEDI0382 are reported. | Pre-dose (Day -2), Days 7, 14, 35, 42, 56; Day 21 of 3 week treatment extension, and 28 days post last dose (approximately 5 months) |
| Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM) | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. During 14 days follow-up (Day 91), last observation carried forward (LOCF) approach was used to calculate the value. | Baseline (Day -1) through Day 56 (end of the up-titration period), Day 77 (end of the treatment extension period) and Day 91 (end of the follow-up period) |
| Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. | Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period |
| Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM | Change from baseline in percentage of glucose AUC4Hrs during a standardized breakfast, lunch, and evening meal over time is reported. Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. | Baseline (Day -1) through Day 7 (end of Week 1), Day 56 (end of the up-titration period), and Day 77 (end of the treatment extension period) |
| Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Change from baseline in coefficient of variation in glucose over 7 days is reported. | Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period |
| Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (< 54 mg/dL). | Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period) |
| Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (< 54 mg/dL). | Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period |
| Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time | Change from baseline in estimated HbA1c based on 7-day glucose over time is reported. | Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period |
| Change From Baseline in Fasting Plasma Glucose Over Time | Change from baseline in fasting plasma glucose over time is reported. During the Day 21, and Day 28, LOCF approach was used to calculate the value. | Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period) |
| Change From Baseline in HbA1c | Change from baseline in HbA1c is reported. | Baseline (Day -1) through Day 77 (end of the treatment extension period) |
| Absolute Change From Baseline in Body Weight | Absolute change from baseline in body weight is reported. | Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP) |
| Percentage Change From Baseline in Body Weight | Percentage change from baseline in body weight is reported. | Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP) |
| Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period | Absolute change from baseline in body weight to the end of each week of the up-titration period is reported. | Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56 |
| Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period | Percentage change from baseline in body weight to the end of each week of the up-titration period is reported. | Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56 |
| Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period | Percentage of participants achieving greater than 5% body weight loss from baseline is reported. | Baseline (Day -1) through Day 77 (end of the treatment extension period) |
| Not-specifed |
|
Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP. |
| BG002 | Placebo Cohort 2 | Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP. |
| BG003 | MEDI0382 Cohort 2 | Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP. |
| BG004 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 | Placebo Cohort 1 | Participants received subcutaneous (SC) dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week treatment extension period (TEP). |
| OG001 | MEDI0382 Cohort 1 | Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP. |
| OG002 | Placebo Cohort 2 | Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP. |
| OG003 | MEDI0382 Cohort 2 | Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP. |
|
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| Primary | Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period | An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
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|
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| Primary | Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period | Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG. | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day -1) through Day 56 (end of Up-titration period) |
|
|
|
| Primary | Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period | Number of participants with abnormal ECGs reported as TEAEs are reported. Abnormal ECGs is defined as any abnormal findings in heart rate, RR interval, PR interval, QRS, QT intervals, and QTcF intervals from the primary lead of the digital 12-lead ECG. | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
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| Primary | Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period | Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day -1) through Day 56 (end of Up-titration period) |
|
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| Primary | Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period | Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
|
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| Primary | Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period | Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examinations findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and, endocrine. | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day -1) through Day 56 (end of Up-titration period) |
|
|
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| Primary | Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period | Number of participants with abnormal physical examinations reported as TEAEs are reported. Abnormal physical examination findings are defined as any abnormal finding in the following body systems: immunologic/allergy; head, ears, eyes, nose, and throat; respiratory; cardiovascular; gastrointestinal; musculoskeletal; neurological psychiatric; dermatologic; hematologic/lymphatic; and endocrine. | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
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| Primary | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine. | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day -1) through Day 56 (end of Up-titration period) |
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| Primary | Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period | Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine. | As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received. | Posted | Count of Participants | Participants | Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months) |
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| Secondary | Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 | Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 is reported. | Pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points. | Posted | Geometric Mean | Full Range | ng.hr/mL | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
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| Secondary | Maximum Observed Serum Concentration (Cmax) of MEDI0382 | Maximum observed serum concentration (Cmax) of MEDI0382 is reported. | The PK population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points. | Posted | Geometric Mean | Full Range | ng/mL | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
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| Secondary | Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 | Time to observed maximum serum concentration (Tmax) of MEDI0382 is reported. | The PK population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points. | Posted | Median | Full Range | hours | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
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| Secondary | Trough Plasma Concentration (Ctrough) of MEDI0382 | Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration (Ctrough) of MEDI0382 is reported. | The PK population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points. | Posted | Geometric Mean | Full Range | ng/mL | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
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| Secondary | Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC | The Ro was calculated using the AUC method which account for the overall exposure measured using the Day 1 and specified time point (Day I). Ro = AUCtrough [Day I]/AUCtrough [Day 1]; where I is the specified day. | The PK population included all participants who received at least 1 dose of study drug and had at least one measurable concentration time point of MEDI0382. Here, only the participants with available data were analyzed for the specified time points. | Posted | Geometric Mean | Full Range | Ratio | Pre-dose and at 1, 2, 4, 6, 8, 12 and 24 hours post dose on Days 1, 7, 14, 35, 42, 49 and 56; pre-dose on Days 22, 29, 70, 84; additional 48 and 72 hours post-dose on Day 84 |
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| Secondary | Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment | Number of participants with positive ADA to MEDI0382 are reported. | Immunogenicity population included all participants who received any dose of study drug, and had at least one serum sample for immunogenicity testing. | Posted | Count of Participants | Participants | Pre-dose (Day -2), Days 7, 14, 35, 42, 56; Day 21 of 3 week treatment extension, and 28 days post last dose (approximately 5 months) |
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| Secondary | Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM) | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. During 14 days follow-up (Day 91), last observation carried forward (LOCF) approach was used to calculate the value. | Intent-to-treat (ITT) population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | mg/dL | Baseline (Day -1) through Day 56 (end of the up-titration period), Day 77 (end of the treatment extension period) and Day 91 (end of the follow-up period) |
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| Secondary | Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | mg/dL | Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period |
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| Secondary | Percentage Change From Baseline in Glucose Area Under Concentration Time-curve Over 4 Hours (AUC4Hrs) During a Standardized Breakfast, Lunch, and Evening Meal Over Time as Measured by CGM | Change from baseline in percentage of glucose AUC4Hrs during a standardized breakfast, lunch, and evening meal over time is reported. Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | Percent change in Glucose AUC4Hrs | Baseline (Day -1) through Day 7 (end of Week 1), Day 56 (end of the up-titration period), and Day 77 (end of the treatment extension period) |
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| Secondary | Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Change from baseline in coefficient of variation in glucose over 7 days is reported. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | Percent of CV | Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period |
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| Secondary | Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (< 54 mg/dL). | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | Percentage of time spent | Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period) |
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| Secondary | Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM | Continuous glucose monitoring is a minimally invasive device applied to the skin in the upper arm that provides a measure of interstitial glucose levels every 15 minutes. Data derived from CGM was used to calculate the average glucose level over 24-hour and 7-day periods to compare the glucose lowering efficacy of each dose level. Hyperglycemia (> 140 mg/dL), normoglycemia (70 -140 mg/dL), and clinically significant hypoglycemia (< 54 mg/dL). | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | Percentage of time spent | Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period |
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| Secondary | Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time | Change from baseline in estimated HbA1c based on 7-day glucose over time is reported. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | Percent of HbA1C | Baseline (Days -7 to -1), Days 1-7, Days 8-14, Days 15-21, Days 22-28, Days 29-35, Days 36-42, Days 43-49, Days 50-56 of the Up-titration period, and Days 71-77 of end of the treatment extension period |
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| Secondary | Change From Baseline in Fasting Plasma Glucose Over Time | Change from baseline in fasting plasma glucose over time is reported. During the Day 21, and Day 28, LOCF approach was used to calculate the value. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | mg/dL | Baseline (Day -1), Days 7, 14, 21, 28, 35, 42, 49, 56 of the up-titration period, and Day77 (end of the treatment extension period) |
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| Secondary | Change From Baseline in HbA1c | Change from baseline in HbA1c is reported. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. | Posted | Mean | Standard Deviation | Percent of HbA1C | Baseline (Day -1) through Day 77 (end of the treatment extension period) |
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| Secondary | Absolute Change From Baseline in Body Weight | Absolute change from baseline in body weight is reported. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | Kg | Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP) |
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| Secondary | Percentage Change From Baseline in Body Weight | Percentage change from baseline in body weight is reported. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | Percentage change in body weight | Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP) |
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| Secondary | Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period | Absolute change from baseline in body weight to the end of each week of the up-titration period is reported. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | Kg | Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56 |
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| Secondary | Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period | Percentage change from baseline in body weight to the end of each week of the up-titration period is reported. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Mean | Standard Deviation | Percentage change in body weight | Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56 |
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| Secondary | Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period | Percentage of participants achieving greater than 5% body weight loss from baseline is reported. | An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group. Here, only the participants with available data were analyzed for the specified time points. | Posted | Number | Percentage of participants | Baseline (Day -1) through Day 77 (end of the treatment extension period) |
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| 0 |
| 2 |
| 0 |
| 2 |
| 2 |
| 2 |
| EG001 | MEDI0382 Cohort 1 | Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP. | 0 | 6 | 0 | 6 | 6 | 6 |
| EG002 | Placebo Cohort 2 | Participants received SC dose of placebo matched to MEDI0382 once daily up to 8 weeks during the up-titration period and thereafter once daily through 3 week TEP. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG003 | MEDI0382 Cohort 2 | Participants received SC dose of MEDI0382 up-titrated weekly once daily up to 8 weeks during the up-titration period and thereafter once daily in 3-week TEP. | 0 | 9 | 0 | 9 | 8 | 9 |
| Supraventricular extrasystoles | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
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| Ventricular extrasystoles | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
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| Ventricular tachycardia | Cardiac disorders | MedDRA 22.0 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 22.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Eructation | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Intra-abdominal haematoma | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Early satiety | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Herpes zoster | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Blood pressure diastolic increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Appetite disorder | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
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| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 22.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Lethargy | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| TESAEs |
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| Supraventricular extrasystoles |
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| Ventricular extrasystoles |
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| Ventricular tachycardia |
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| Supraventricular extrasystoles |
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| Ventricular extrasystoles |
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| Ventricular tachycardia |
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| Day 14 |
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| Day 35 |
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| Day 42 |
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| Day 49 |
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| Day 56 |
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| Day 84 |
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| Day 14 |
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| Day 35 |
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| Day 42 |
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| Day 49 |
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| Day 56 |
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| Day 84 |
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| Day 14 |
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| Day 35 |
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| Day 42 |
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| Day 49 |
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| Day 56 |
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| Day 84 |
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| Day 14 |
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| Day 22 |
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| Day 29 |
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| Day 35 |
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| Day 42 |
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| Day 49 |
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| Day 56 |
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| Day 70 |
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| Day 84 |
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| Day 14 |
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| Day 35 |
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| Day 42 |
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| Day 49 |
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| Day 56 |
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| Day 84 |
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| Positive post-baseline |
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| Positive at baseline and post-baseline |
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| Not detected at baseline; positive post-baseline |
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| Positive at baseline; not detected post-baseline |
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| Day 77 |
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| Day 91 |
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| Days 8-14 |
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| Days 15-21 |
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| Days 22-28 |
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| Days 29-35 |
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| Days 36-42 |
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| Days 43-49 |
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| Days 50-56 |
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| Days 71-77 |
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| Day 56 - Breakfast |
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| Day 77 - Breakfast |
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| Day 7 - Lunch |
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| Day 56 - Lunch |
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| Day 77 - Lunch |
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| Day 7 - Evening Meal |
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| Day 56 - Evening Meal |
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| Day 77 - Evening Meal |
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| Days 8 - 14 |
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| Days 15 - 21 |
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| Days 22 - 28 |
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| Days 29 - 35 |
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| Days 36 - 42 |
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| Days 43 - 49 |
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| Days 50 - 56 |
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| Days 71 - 77 |
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| Day 14 - Hyperglycemia |
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| Day 21 - Hyperglycemia |
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| Day 28 - Hyperglycemia |
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| Day 35 - Hyperglycemia |
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| Day 42 - Hyperglycemia |
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| Day 49 - Hyperglycemia |
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| Day 56 - Hyperglycemia |
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| Day 77 - Hyperglycemia |
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| Day 7 - Normoglycemia |
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| Day 14 - Normoglycemia |
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| Day 21 - Normoglycemia |
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| Day 28 - Normoglycemia |
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| Day 35 - Normoglycemia |
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| Day 42 - Normoglycemia |
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| Day 49 - Normoglycemia |
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| Day 56 - Normoglycemia |
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| Day 77 - Normoglycemia |
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| Day 7 - Hypoglycemia |
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| Day 14 - Hypoglycemia |
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| Day 21 - Hypoglycemia |
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| Day 28 - Hypoglycemia |
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| Day 35 - Hypoglycemia |
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| Day 42 - Hypoglycemia |
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| Day 49 - Hypoglycemia |
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| Day 56 - Hypoglycemia |
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| Day 77 - Hypoglycemia |
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| Days 8 - 14 (Hyperglycemia) |
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| Days 15 - 21 (Hyperglycemia) |
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| Days 22 - 28 (Hyperglycemia) |
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| Days 29 - 35 (Hyperglycemia) |
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| Days 36 - 42 (Hyperglycemia) |
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| Days 43 - 49 (Hyperglycemia) |
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| Days 50 - 56 (Hyperglycemia) |
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| Days 71 - 77 (Hyperglycemia) |
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| Days 1 - 7 (Normoglycemia) |
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| Days 8 - 14 Normoglycemia) |
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| Days 15 - 21 (Normoglycemia) |
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| Days 22 - 28 (Normoglycemia) |
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| Days 29 - 35 (Normoglycemia) |
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| Days 36 - 42 (Normoglycemia) |
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| Days 43 - 49 (Normoglycemia) |
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| Days 50 - 56 (Normoglycemia) |
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| Days 71 - 77 (Normoglycemia) |
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| Days 1 - 7 (Hypoglycemia) |
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| Days 8 - 14 (Hypoglycemia) |
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| Days 15 - 21 (Hypoglycemia) |
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| Days 22 - 28 Hypoglycemia) |
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| Days 29 - 35 (Hypoglycemia) |
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| Days 36 - 42 (Hypoglycemia) |
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| Days 43 - 49 (Hypoglycemia) |
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| Days 50 - 56 (Hypoglycemia) |
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| Days 71 - 77 (Hypoglycemia) |
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| Days 8 - 14 |
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| Days 15 - 21 |
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| Days 22 - 28 |
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| Days 29 - 35 |
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| Days 36 - 42 |
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| Days 43 - 49 |
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| Days 50 - 56 |
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| Days 71 - 77 |
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| Day 14 |
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| Day 21 |
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| Day 28 |
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| Day 35 |
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| Day 42 |
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| Day 49 |
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| Day 56 |
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| Day 77 |
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| Day 77 |
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| Day 77 |
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| Day 14 |
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| Day 35 |
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| Day 42 |
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| Day 49 |
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| Day 56 |
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| Day 14 |
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| Day 35 |
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| Day 42 |
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| Day 49 |
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| Day 56 |
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| Day 14 |
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| Day 35 |
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| Day 42 |
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| Day 49 |
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| Day 56 |
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| Day 77 |
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