A Study to Evaluate the Safety and Tolerability of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus

• Sponsor: MedImmune LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03745937
• Collaborator: (none)
• Enrollment: 20
• Location: 1
• Arms: 4
• Actual Duration (Months): 4.6
• Patients Per Site Per Month: 4.3

Study Details

Study Description

Brief Summary

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.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MEDI0382 in Overweight/Obese Subjects With Type 2 Diabetes Mellitus
• Actual Study Start Date: Jan 7, 2019
• Actual Primary Completion Date: May 28, 2019
• Actual Study Completion Date: May 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI0382 Cohort 1 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).	Drug: MEDI0382; 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.
Placebo Comparator: Placebo Cohort 1 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.	Drug: Placebo; 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.
Experimental: MEDI0382 Cohort 2 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.	Drug: MEDI0382; 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.
Placebo Comparator: Placebo Cohort 2 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.	Drug: Placebo; 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.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period [Baseline (Day -1) through Day 56 (end of 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.

2. Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period [Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)]

   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.

3. Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period [Baseline (Day -1) through Day 56 (end of 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.

4. Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period [Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)]

   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.

5. Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period [Baseline (Day -1) through Day 56 (end of 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).

6. Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period [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 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).

7. Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period [Baseline (Day -1) through Day 56 (end of 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.

8. Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period [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 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.

9. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period [Baseline (Day -1) through Day 56 (end of 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.

10. Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period [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 are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of serum chemistry, hematology, and urine.

Secondary Outcome Measures

1. Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382 [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]

   Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 is reported.

2. Maximum Observed Serum Concentration (Cmax) of MEDI0382 [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]

   Maximum observed serum concentration (Cmax) of MEDI0382 is reported.

3. Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 [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 is reported.

4. Trough Plasma Concentration (Ctrough) of MEDI0382 [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 concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration (Ctrough) of MEDI0382 is reported.

5. Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC [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]

   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.

6. Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment [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)]

   Number of participants with positive ADA to MEDI0382 are reported.

7. Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM) [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)]

   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.

8. Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM [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]

   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.

9. 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 [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 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.

10. Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM [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]

    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.

11. Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM [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)]

    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).

12. Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM [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]

    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).

13. Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time [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 HbA1c based on 7-day glucose over time is reported.

14. Change From Baseline in Fasting Plasma Glucose Over Time [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 fasting plasma glucose over time is reported. During the Day 21, and Day 28, LOCF approach was used to calculate the value.

15. Change From Baseline in HbA1c [Baseline (Day -1) through Day 77 (end of the treatment extension period)]

    Change from baseline in HbA1c is reported.

16. Absolute Change From Baseline in Body Weight [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 is reported.

17. Percentage Change From Baseline in Body Weight [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 is reported.

18. Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period [Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56]

    Absolute change from baseline in body weight to the end of each week of the up-titration period is reported.

19. Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period [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 is reported.

20. Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period [Baseline (Day -1) through Day 77 (end of the treatment extension period)]

    Percentage of participants achieving greater than 5% body weight loss from baseline is reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participants aged 18 to 74 years (inclusive) at screening.

2. Provision of signed and dated written informed consent (with the exception of consent for genetic and non-genetic research) prior to any study specific procedures.

3. Body mass index (BMI) between 27 and 35 kg/m^2 (inclusive) at screening.

4. Hemoglobin A1c (HbA1c) range of 6.5% to 8.5% (inclusive) at screening (Note: Participants may be re-tested for the HbA1c entry criterion only once.).

5. Willing and able to self-inject study drug for the duration of the study.

6. Diagnosed with type 2 diabetes mellitus with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease >= 500 mg/day) has occurred in the three months prior to screening.

7. Female participants must have a negative pregnancy test at screening and randomization, and must not be lactating.

8. Female participants of childbearing potential who are sexually active with a male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose of study drug.

Exclusion Criteria:

1. 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.

2. 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.

3. Concurrent participation in another study of any kind and repeat randomization in this study is prohibited.

4. Any participant who has received any of the following medications prior to the start of the study:

• Herbal preparations or drugs licensed for control of body weight or appetite

• Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying

• Antimicrobials within the quinolone, macrolide or azole class

• Any change in antihypertensive medication

• Aspirin (acetylsalicylic acid)

• Paracetamol (acetaminophen) or paracetamol-containing preparations

• Ascorbic acid (vitamin C) supplements

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

2. 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.

3. 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.

4. 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.

5. 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:

• Aspartate transaminase (AST) >= 3 × ULN

• Alanine transaminase (ALT) >= 3 × ULN

• Total bilirubin (TBL) >= 2 × ULN

1. Impaired renal function defined as estimated glomerular filtration rate (GFR) < 60 mL/minute/1.73m^2 at screening.

2. Poorly controlled hypertension defined as:

• Systolic blood pressure (BP) > 160 mm Hg

• Diastolic BP or >= 90 mm Hg

1. 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.

2. Prolonged QT intervals corrected for heart rate or family history of long QT-segment at screening.

3. PR (PQ) interval prolongation, intermittent second or third-degree atrioventricular (AV) block, or AV dissociation.

4. Persistent or intermittent complete bundle branch block.

5. 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.

6. Severe congestive heart failure.

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

8. Hemoglobinopathy, hemolytic anemia or chronic anemia or any other condition known to interfere with the interpretation of HbA1c measurement.

9. 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.

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

11. 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.

12. Symptoms of depression or any other psychiatric disorder requiring treatment with medication.

13. History of severe allergy/hypersensitivity, including to any component of the investigational product formulation or other biological agent, or ongoing clinically important allergy/hypersensitivity.

14. Blood/plasma donation within 1 month of screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Neuss		Germany	41460

Sponsors and Collaborators

• MedImmune LLC

Investigators

• Principal Investigator: Tim Heise, MD, Profil Institut für Stoffwechselforschung GmbH

Study Documents (Full-Text)

• Study Protocol - Apr 16, 2019
• Statistical Analysis Plan - Jan 22, 2019

More Information

Additional Information:

• CSP redacted protocol
• SAP redacted

Publications

None provided.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT03745937
• Other Study ID Numbers: D5670C00030
• First Posted: Nov 19, 2018
• Last Update Posted: Jun 5, 2020
• Last Verified: May 1, 2020

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

Study Results

Participant Flow

Recruitment Details	The study was conducted in Germany between 07Jan2019 and 28May2019.
Pre-assignment Detail	A total of 20 participants were randomized to the study.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Period Title: Overall Study
STARTED	2	6	3	9
COMPLETED	2	5	3	7
NOT COMPLETED	0	1	0	2

Baseline Characteristics

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2	Total
Arm/Group Description	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).	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.	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.	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.	Total of all reporting groups
Overall Participants	2	6	3	9	20
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.5 (3.5)	65.3 (6.2)	62.3 (3.5)	67.1 (5.3)	66.0 (5.2)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 16.7%	2 66.7%	2 22.2%	5 25%
Male	2 100%	5 83.3%	1 33.3%	7 77.8%	15 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	6 100%	3 100%	9 100%	20 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%
White	2 100%	6 100%	3 100%	9 100%	20 100%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period
Description	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; 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.
Time Frame	Baseline (Day -1) through Day 56 (end of Up-titration period)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
TEAEs	2 100%	6 100%	3 100%	8 88.9%
TESAEs	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period
Description	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.
Time Frame	Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
TEAEs	2 100%	6 100%	3 100%	8 88.9%
TESAEs	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period
Description	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.
Time Frame	Baseline (Day -1) through Day 56 (end of Up-titration period)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Atrial fibrillation	0 0%	0 0%	0 0%	1 11.1%
Supraventricular extrasystoles	0 0%	0 0%	0 0%	1 11.1%
Ventricular extrasystoles	0 0%	0 0%	0 0%	1 11.1%
Ventricular tachycardia	1 50%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period
Description	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.
Time Frame	Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Atrial fibrillation	0 0%	0 0%	0 0%	1 11.1%
Supraventricular extrasystoles	0 0%	0 0%	0 0%	1 11.1%
Ventricular extrasystoles	0 0%	0 0%	0 0%	1 11.1%
Ventricular tachycardia	1 50%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period
Description	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).
Time Frame	Baseline (Day -1) through Day 56 (end of Up-titration period)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Count of Participants [Participants]	0 0%	1 16.7%	0 0%	0 0%

6. Primary Outcome

Title	Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period
Description	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).
Time Frame	Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Count of Participants [Participants]	0 0%	1 16.7%	0 0%	0 0%

7. Primary Outcome

Title	Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period
Description	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.
Time Frame	Baseline (Day -1) through Day 56 (end of Up-titration period)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Count of Participants [Participants]	0 0%	3 50%	0 0%	4 44.4%

8. Primary Outcome

Title	Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period
Description	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.
Time Frame	Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Count of Participants [Participants]	0 0%	3 50%	0 0%	4 44.4%

9. Primary Outcome

Title	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period
Description	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.
Time Frame	Baseline (Day -1) through Day 56 (end of Up-titration period)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Count of Participants [Participants]	0 0%	1 16.7%	0 0%	0 0%

10. Primary Outcome

Title	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period
Description	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.
Time Frame	Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Outcome Measure Data

Analysis Population Description

As-treated population included all participants who received any dose of study drug and analyzed according to the treatment they actually received.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Count of Participants [Participants]	0 0%	1 16.7%	0 0%	0 0%

11. Secondary Outcome

Title	Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382
Description	Area under the plasma concentration time curve over a dosing duration (AUCτ) of MEDI0382 is reported.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MEDI0382 (Cohort 1 + Cohort 2)
Arm/Group Description	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, in both Cohorts 1 and 2.
Measure Participants	15
Day 1	20.9
Day 7	23.7
Day 14	59.9
Day 35	276
Day 42	332
Day 49	434
Day 56	611
Day 84	661

12. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax) of MEDI0382
Description	Maximum observed serum concentration (Cmax) of MEDI0382 is reported.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MEDI0382 (Cohort 1 + Cohort 2)
Arm/Group Description	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, in both Cohorts 1 and 2.
Measure Participants	15
Day 1	1.02
Day 7	1.35
Day 14	3.43
Day 35	15.3
Day 42	17.8
Day 49	24.9
Day 56	32.8
Day 84	35.3

13. Secondary Outcome

Title	Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382
Description	Time to observed maximum serum concentration (Tmax) of MEDI0382 is reported.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MEDI0382 (Cohort 1 + Cohort 2)
Arm/Group Description	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, in both Cohorts 1 and 2.
Measure Participants	15
Day 1	6.02
Day 7	6.00
Day 14	6.00
Day 35	6.00
Day 42	6.00
Day 49	6.00
Day 56	6.00
Day 84	6.00

14. Secondary Outcome

Title	Trough Plasma Concentration (Ctrough) of MEDI0382
Description	Trough concentration is the lowest concentration reached by a drug before the next dose is administered. Trough plasma concentration (Ctrough) of MEDI0382 is reported.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MEDI0382 (Cohort 1 + Cohort 2)
Arm/Group Description	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, in both Cohorts 1 and 2.
Measure Participants	15
Day 7	0.551
Day 14	1.46
Day 22	2.01
Day 29	4.65
Day 35	6.92
Day 42	8.85
Day 49	11.0
Day 56	16.3
Day 70	13.6
Day 84	18.8

15. Secondary Outcome

Title	Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	MEDI0382 (Cohort 1 + Cohort 2)
Arm/Group Description	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, in both Cohorts 1 and 2.
Measure Participants	15
Day 1	NA
Day 7	1.25
Day 14	1.40
Day 35	1.01
Day 42	0.857
Day 49	0.904
Day 56	1.16
Day 84	1.30

16. Secondary Outcome

Title	Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment
Description	Number of participants with positive ADA to MEDI0382 are reported.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Immunogenicity population included all participants who received any dose of study drug, and had at least one serum sample for immunogenicity testing.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Positive at baseline	0 0%	0 0%	0 0%	1 11.1%
Positive post-baseline	0 0%	3 50%	0 0%	4 44.4%
Positive at baseline and post-baseline	0 0%	0 0%	0 0%	1 11.1%
Not detected at baseline; positive post-baseline	0 0%	3 50%	0 0%	3 33.3%
Positive at baseline; not detected post-baseline	0 0%	0 0%	0 0%	1 11.1%

17. Secondary Outcome

Title	Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM)
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Day 56	-14.96 (16.06)	-52.04 (21.73)	-22.51 (22.41)	-34.25 (14.69)
Day 77	-10.41 (0.17)	-49.24 (25.81)	-32.54 (26.78)	-39.70 (21.85)
Day 91	-1.80 (25.06)	-5.71 (29.28)	20.28 (33.40)	-13.03 (24.54)

18. Secondary Outcome

Title	Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Days 1-7	37.53 (NA)	-34.64 (15.48)	-3.96 (3.30)	-26.06 (9.47)
Days 8-14	22.73 (NA)	-52.07 (19.14)	-14.44 (9.33)	-39.86 (10.44)
Days 15-21	13.83 (NA)	-44.84 (22.06)	-13.72 (18.47)	-38.10 (16.50)
Days 22-28	12.54 (NA)	-53.38 (29.90)	5.88 (7.54)	-25.10 (33.72)
Days 29-35	16.11 (NA)	-63.28 (22.23)	0.32 (13.60)	-40.83 (20.31)
Days 36-42	22.29 (NA)	-47.97 (24.65)	-20.03 (7.97)	-35.45 (26.96)
Days 43-49	5.69 (NA)	-48.06 (19.98)	-19.88 (29.62)	-46.84 (20.92)
Days 50-56	2.02 (NA)	-55.21 (22.32)	-19.59 (21.63)	-37.89 (18.28)
Days 71-77	21.50 (NA)	-62.66 (28.88)	-19.06 (23.43)	-40.20 (31.70)

19. Secondary Outcome

Title	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
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Day 7 - Breakfast	-3.72 (5.73)	-27.90 (2.98)	-8.66 (6.75)	-25.85 (7.33)
Day 56 - Breakfast	-21.96 (13.09)	-42.22 (10.32)	-10.18 (9.18)	-32.82 (10.82)
Day 77 - Breakfast	-10.54 (6.18)	-41.52 (9.97)	-19.21 (7.20)	-32.48 (12.18)
Day 7 - Lunch	-3.06 (23.08)	-32.55 (10.32)	0.32 (9.00)	-15.68 (17.75)
Day 56 - Lunch	-7.35 (11.46)	-33.67 (22.60)	-24.06 (10.65)	-18.30 (13.96)
Day 77 - Lunch	-7.76 (20.13)	-31.10 (32.74)	-28.75 (15.12)	-21.58 (15.09)
Day 7 - Evening Meal	-7.81 (17.77)	-16.14 (15.55)	-10.37 (11.55)	-22.58 (8.20)
Day 56 - Evening Meal	-11.07 (1.26)	-35.39 (22.14)	-22.08 (13.93)	-31.44 (10.51)
Day 77 - Evening Meal	-12.12 (4.61)	-26.09 (21.61)	-22.06 (14.63)	-34.18 (15.11)

20. Secondary Outcome

Title	Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Days 1 - 7	-4.48 (NA)	-0.96 (4.99)	1.51 (3.84)	-2.41 (3.60)
Days 8 - 14	-3.67 (NA)	-2.97 (4.34)	2.26 (3.54)	-0.95 (5.62)
Days 15 - 21	-8.86 (NA)	-2.65 (5.40)	-1.54 (1.05)	-4.44 (2.77)
Days 22 - 28	-4.79 (NA)	-3.70 (6.86)	-2.49 (2.41)	-1.56 (5.23)
Days 29 - 35	-7.92 (NA)	-5.84 (5.42)	-3.24 (1.68)	-2.52 (5.57)
Days 36 - 42	0.93 (NA)	-4.96 (6.54)	1.39 (1.69)	-1.38 (4.68)
Days 43 - 49	-3.96 (NA)	-3.68 (5.42)	2.18 (5.40)	-1.98 (3.48)
Days 50 - 56	-2.97 (NA)	-2.94 (4.61)	4.10 (2.60)	-2.36 (3.23)
Days 71 - 77	-4.91 (NA)	-2.15 (4.88)	2.60 (2.21)	-0.82 (3.73)

21. Secondary Outcome

Title	Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM
Description	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).
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Day 7 - Hyperglycemia	-19.79 (32.41)	-39.06 (15.18)	-7.29 (14.77)	-22.66 (18.06)
Day 14 - Hyperglycemia	-5.73 (12.52)	-41.67 (12.17)	-15.63 (27.14)	-25.91 (24.31)
Day 21 - Hyperglycemia	-3.65 (8.10)	-38.50 (13.38)	10.42 (16.04)	-22.92 (30.64)
Day 28 - Hyperglycemia	-9.90 (18.41)	-33.54 (28.12)	13.19 (33.09)	-21.88 (25.20)
Day 35 - Hyperglycemia	-6.01 (6.84)	-51.24 (8.80)	2.49 (25.74)	-32.30 (27.21)
Day 42 - Hyperglycemia	-19.80 (7.37)	-38.33 (28.49)	-20.49 (32.81)	-36.85 (27.44)
Day 49 - Hyperglycemia	9.90 (19.89)	-49.79 (5.58)	-16.32 (41.07)	-42.71 (27.02)
Day 56 - Hyperglycemia	-20.31 (3.68)	-50.21 (18.51)	-16.96 (26.89)	-31.40 (28.11)
Day 77 - Hyperglycemia	-21.35 (14.00)	-46.04 (20.90)	-26.74 (30.09)	-35.27 (32.58)
Day 7 - Normoglycemia	19.27 (31.67)	39.58 (13.79)	7.64 (15.36)	22.66 (18.04)
Day 14 - Normoglycemia	5.21 (11.79)	41.25 (10.25)	13.89 (29.47)	25.78 (24.35)
Day 21 - Normoglycemia	3.13 (8.84)	39.06 (14.23)	-11.11 (16.84)	19.53 (30.77)
Day 28 - Normoglycemia	9.90 (18.41)	20.21 (18.69)	-13.54 (34.34)	21.13 (25.07)
Day 35 - Normoglycemia	5.48 (7.60)	39.35 (10.46)	-2.14 (26.29)	27.81 (27.30)
Day 42 - Normoglycemia	19.79 (7.37)	34.58 (26.78)	16.67 (37.80)	36.72 (27.45)
Day 49 - Normoglycemia	-10.42 (20.62)	47.92 (5.46)	4.86 (37.81)	41.82 (28.31)
Day 56 - Normoglycemia	19.79 (4.42)	40.42 (24.78)	17.31 (27.47)	30.51 (29.37)
Day 77 - Normoglycemia	18.75 (14.73)	43.13 (19.72)	21.88 (29.04)	27.73 (36.31)
Day 7 - Hypoglycemia	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 14 - Hypoglycemia	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 21 - Hypoglycemia	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 28 - Hypoglycemia	0.00 (0.00)	1.04 (2.33)	0.00 (0.00)	0.00 (0.00)
Day 35 - Hypoglycemia	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 42 - Hypoglycemia	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 49 - Hypoglycemia	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 56 - Hypoglycemia	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Day 77 - Hypoglycemia	0.00 (0.00)	0.83 (1.86)	0.00 (0.00)	1.73 (3.73)

22. Secondary Outcome

Title	Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM
Description	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).
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Days 1 - 7 (Hyperglycemia)	20.70 (NA)	-32.73 (12.03)	-8.87 (5.08)	-23.38 (15.92)
Days 8 - 14 (Hyperglycemia)	17.22 (NA)	-46.85 (16.11)	-17.00 (10.30)	-35.82 (20.15)
Days 15 - 21 (Hyperglycemia)	19.80 (NA)	-40.52 (19.30)	-9.16 (14.98)	-33.74 (26.94)
Days 22 - 28 (Hyperglycemia)	12.25 (NA)	-40.92 (29.12)	6.55 (12.31)	-26.31 (25.76)
Days 29 - 35 (Hyperglycemia)	20.10 (NA)	-51.69 (17.49)	4.03 (15.26)	-38.19 (31.32)
Days 36 - 42 (Hyperglycemia)	11.77 (NA)	-42.48 (25.55)	-17.21 (7.69)	-37.81 (30.52)
Days 43 - 49 (Hyperglycemia)	9.08 (NA)	-41.92 (19.10)	-16.46 (21.74)	-44.62 (30.95)
Days 50 - 56 (Hyperglycemia)	6.82 (NA)	-47.70 (21.30)	-18.70 (16.86)	-34.90 (27.76)
Days 71 - 77 (Hyperglycemia)	18.57 (NA)	-53.98 (27.16)	-16.06 (17.53)	-40.21 (37.99)
Days 1 - 7 (Normoglycemia)	-19.94 (NA)	32.58 (11.48)	9.10 (5.99)	23.34 (15.55)
Days 8 - 14 Normoglycemia)	-16.47 (NA)	43.41 (11.65)	17.07 (10.85)	33.32 (20.61)
Days 15 - 21 (Normoglycemia)	-19.20 (NA)	40.36 (19.14)	9.30 (15.08)	31.82 (27.12)
Days 22 - 28 (Normoglycemia)	-12.10 (NA)	32.09 (24.74)	-6.27 (12.58)	22.44 (26.08)
Days 29 - 35 (Normoglycemia)	-19.49 (NA)	42.95 (16.13)	-3.71 (15.81)	36.13 (30.86)
Days 36 - 42 (Normoglycemia)	-11.31 (NA)	40.62 (24.51)	17.15 (8.75)	37.45 (29.72)
Days 43 - 49 (Normoglycemia)	-8.63 (NA)	40.85 (17.93)	14.07 (19.02)	42.81 (30.11)
Days 50 - 56 (Normoglycemia)	-6.37 (NA)	44.10 (19.74)	18.10 (14.94)	33.61 (27.62)
Days 71 - 77 (Normoglycemia)	-18.27 (NA)	46.39 (29.99)	15.08 (17.47)	37.93 (38.28)
Days 1 - 7 (Hypoglycemia)	0.00 (NA)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Days 8 - 14 (Hypoglycemia)	0.00 (NA)	1.20 (1.68)	0.00 (0.00)	0.28 (0.68)
Days 15 - 21 (Hypoglycemia)	0.00 (NA)	0.00 (0.00)	0.00 (0.00)	0.20 (0.49)
Days 22 - 28 Hypoglycemia)	0.00 (NA)	1.09 (2.28)	0.00 (0.00)	0.79 (1.76)
Days 29 - 35 (Hypoglycemia)	0.00 (NA)	0.27 (0.61)	0.00 (0.00)	0.00 (0.00)
Days 36 - 42 (Hypoglycemia)	0.00 (NA)	0.00 (0.00)	0.00 (0.00)	0.00 (0.00)
Days 43 - 49 (Hypoglycemia)	0.00 (NA)	0.09 (0.20)	0.40 (0.70)	0.15 (0.37)
Days 50 - 56 (Hypoglycemia)	0.00 (NA)	0.06 (0.14)	0.20 (0.35)	0.15 (0.37)
Days 71 - 77 (Hypoglycemia)	0.00 (NA)	2.16 (3.23)	0.15 (0.26)	0.44 (0.59)

23. Secondary Outcome

Title	Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time
Description	Change from baseline in estimated HbA1c based on 7-day glucose over time is reported.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Days 1 - 7	1.31 (NA)	-1.21 (0.54)	-0.14 (0.12)	-0.91 (0.33)
Days 8 - 14	0.79 (NA)	-1.81 (0.67)	-0.50 (0.33)	-1.39 (0.36)
Days 15 - 21	0.48 (NA)	-1.56 (0.77)	-0.48 (0.64)	-1.33 (0.58)
Days 22 - 28	0.44 (NA)	-1.86 (1.04)	0.21 (0.26)	-0.88 (1.18)
Days 29 - 35	0.56 (NA)	-2.21 (0.78)	0.01 (0.47)	-1.42 (0.71)
Days 36 - 42	0.78 (NA)	-1.67 (0.86)	-0.70 (0.28)	-1.24 (0.94)
Days 43 - 49	0.20 (NA)	-1.68 (0.70)	-0.69 (1.03)	-1.63 (0.73)
Days 50 - 56	0.07 (NA)	-1.92 (0.78)	-0.68 (0.75)	-1.32 (0.64)
Days 71 - 77	0.75 (NA)	-2.18 (1.01)	-0.66 (0.82)	-1.40 (1.10)

24. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose Over Time
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Day 7	9.0 (48.1)	-32.0 (17.7)	13.7 (7.5)	-27.1 (12.6)
Day 14	-17.5 (31.8)	-48.0 (19.2)	-3.3 (23.9)	-33.9 (19.1)
Day 21	-17.5 (31.8)	-48.0 (19.2)	-3.3 (23.9)	-33.9 (19.1)
Day 28	-17.5 (31.8)	-48.0 (19.2)	-3.3 (23.9)	-33.9 (19.1)
Day 35	28.5 (16.3)	-46.8 (25.8)	5.7 (29.2)	-44.4 (15.8)
Day 42	9.0 (14.1)	-42.6 (24.5)	2.0 (27.9)	-35.1 (24.6)
Day 49	23.5 (20.5)	-45.6 (23.0)	-0.3 (35.6)	-38.1 (23.7)
Day 56	-7.5 (37.5)	-52.8 (24.4)	-9.7 (26.4)	-31.3 (24.6)
Day 77	1.0 (21.2)	-47.6 (34.2)	-9.7 (32.9)	-28.6 (20.5)

25. Secondary Outcome

Title	Change From Baseline in HbA1c
Description	Change from baseline in HbA1c is reported.
Time Frame	Baseline (Day -1) through Day 77 (end of the treatment extension period)

Outcome Measure Data

Analysis Population Description

An ITT population included all participants who received any dose of study drug and analyzed according to their randomized treatment group.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Mean (Standard Deviation) [Percent of HbA1C]	0.10 (0.00)	-1.44 (0.52)	-0.40 (0.35)	-0.59 (0.74)

26. Secondary Outcome

Title	Absolute Change From Baseline in Body Weight
Description	Absolute change from baseline in body weight is reported.
Time Frame	Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Day 56	-0.30 (0.00)	-5.27 (3.92)	-1.70 (1.80)	-2.89 (4.15)
Day 77	-1.25 (0.64)	-6.96 (4.66)	-1.50 (1.56)	-4.56 (4.41)

27. Secondary Outcome

Title	Percentage Change From Baseline in Body Weight
Description	Percentage change from baseline in body weight is reported.
Time Frame	Baseline (Day -1) through Day 56 (end of the up-titration period) and Day 77 (end of the TEP)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Day 56	-0.33 (0.01)	-5.06 (3.16)	-1.96 (2.09)	-3.20 (4.78)
Day 77	-1.38 (0.74)	-6.88 (3.81)	-1.76 (1.79)	-5.08 (5.00)

28. Secondary Outcome

Title	Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period
Description	Absolute change from baseline in body weight to the end of each week of the up-titration period is reported.
Time Frame	Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Day 7	-2.05 (1.06)	-1.78 (0.86)	-0.70 (1.64)	0.49 (4.87)
Day 14	-1.95 (0.35)	-2.72 (0.68)	-0.73 (1.10)	0.08 (4.19)
Day 35	-0.60 (0.99)	-3.86 (3.24)	-0.27 (1.25)	-1.70 (4.37)
Day 42	-0.10 (0.14)	-4.40 (3.22)	-1.57 (1.50)	-2.00 (4.56)
Day 49	0.10 (0.14)	-4.94 (3.63)	-1.57 (1.19)	-3.30 (5.08)
Day 56	-0.30 (0.00)	-5.27 (3.92)	-1.70 (1.80)	-2.89 (4.15)

29. Secondary Outcome

Title	Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period
Description	Percentage change from baseline in body weight to the end of each week of the up-titration period is reported.
Time Frame	Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Day 7	-2.22 (1.09)	-1.83 (0.95)	-0.77 (1.96)	0.67 (5.69)
Day 14	-2.13 (0.32)	-2.76 (0.62)	-0.83 (1.30)	0.22 (4.85)
Day 35	-0.64 (1.06)	-3.89 (2.99)	-0.27 (1.50)	-1.78 (4.95)
Day 42	-0.11 (0.15)	-4.43 (2.93)	-1.81 (1.74)	-2.09 (5.16)
Day 49	0.11 (0.16)	-4.95 (3.32)	-1.82 (1.37)	-3.52 (5.67)
Day 56	-0.33 (0.01)	-5.06 (3.16)	-1.96 (2.09)	-3.20 (4.78)

30. Secondary Outcome

Title	Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period
Description	Percentage of participants achieving greater than 5% body weight loss from baseline is reported.
Time Frame	Baseline (Day -1) through Day 77 (end of the treatment extension period)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Placebo Cohort 1	MEDI0382 Cohort 1	Placebo Cohort 2	MEDI0382 Cohort 2
Arm/Group Description	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).	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.	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.	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.
Measure Participants	2	6	3	9
Day 7	0 0%	0 0%	0 0%	0 0%
Day 14	0 0%	0 0%	0 0%	0 0%
Day 35	0 0%	40 666.7%	0 0%	25 277.8%
Day 42	0 0%	40 666.7%	0 0%	25 277.8%
Day 49	0 0%	60 1000%	0 0%	50 555.6%
Day 56	0 0%	50 833.3%	0 0%	28.6 317.8%
Day 77	0 0%	80 1333.3%	0 0%	71.4 793.3%

Adverse Events

Time Frame	Baseline (Day -1) through 28 days post last dose (approximately up to 5 months)
Arm/Group Title	Placebo Cohort 1		MEDI0382 Cohort 1		Placebo Cohort 2		MEDI0382 Cohort 2
Arm/Group Description	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).		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.		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.		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.
All Cause Mortality
	Placebo Cohort 1		MEDI0382 Cohort 1		Placebo Cohort 2		MEDI0382 Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/6 (0%)		0/3 (0%)		0/9 (0%)
Serious Adverse Events
	Placebo Cohort 1		MEDI0382 Cohort 1		Placebo Cohort 2		MEDI0382 Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/6 (0%)		0/3 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Placebo Cohort 1		MEDI0382 Cohort 1		Placebo Cohort 2		MEDI0382 Cohort 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		6/6 (100%)		3/3 (100%)		8/9 (88.9%)
Cardiac disorders
Atrial fibrillation	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Supraventricular extrasystoles	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Ventricular extrasystoles	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Ventricular tachycardia	1/2 (50%)	1	0/6 (0%)	0	0/3 (0%)	0	0/9 (0%)	0
Ear and labyrinth disorders
Vertigo	0/2 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/9 (11.1%)	1
Gastrointestinal disorders
Abdominal distension	1/2 (50%)	1	1/6 (16.7%)	1	1/3 (33.3%)	1	2/9 (22.2%)	3
Abdominal pain	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/9 (22.2%)	4
Abdominal pain upper	0/2 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/9 (0%)	0
Constipation	0/2 (0%)	0	4/6 (66.7%)	4	1/3 (33.3%)	1	2/9 (22.2%)	3
Diarrhoea	0/2 (0%)	0	2/6 (33.3%)	2	0/3 (0%)	0	3/9 (33.3%)	8
Dyspepsia	0/2 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	4/9 (44.4%)	4
Eructation	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Gastrooesophageal reflux disease	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Intra-abdominal haematoma	0/2 (0%)	0	0/6 (0%)	0	1/3 (33.3%)	1	0/9 (0%)	0
Nausea	0/2 (0%)	0	2/6 (33.3%)	3	0/3 (0%)	0	1/9 (11.1%)	4
Vomiting	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
General disorders
Early satiety	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	4/9 (44.4%)	4
Fatigue	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	2/9 (22.2%)	2
Injection site erythema	0/2 (0%)	0	2/6 (33.3%)	3	0/3 (0%)	0	1/9 (11.1%)	1
Injection site reaction	0/2 (0%)	0	2/6 (33.3%)	4	0/3 (0%)	0	4/9 (44.4%)	15
Infections and infestations
Herpes zoster	0/2 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/9 (0%)	0
Nasopharyngitis	1/2 (50%)	1	2/6 (33.3%)	2	2/3 (66.7%)	4	1/9 (11.1%)	1
Investigations
Blood pressure diastolic increased	0/2 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/9 (0%)	0
Metabolism and nutrition disorders
Appetite disorder	0/2 (0%)	0	4/6 (66.7%)	4	0/3 (0%)	0	0/9 (0%)	0
Decreased appetite	0/2 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/9 (0%)	0
Hyperkalaemia	0/2 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/9 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/2 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/9 (0%)	0
Nervous system disorders
Dizziness	0/2 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/9 (0%)	0
Lethargy	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1
Presyncope	0/2 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	1/9 (11.1%)	2
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/2 (0%)	0	1/6 (16.7%)	1	0/3 (0%)	0	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/2 (0%)	0	0/6 (0%)	0	0/3 (0%)	0	1/9 (11.1%)	1

Limitations/Caveats

[Not Specified]

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