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CompletedNCT03745937Updated Jun 5, 2020Results posted

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

A Phase 2 interventional study of MEDI0382 and Placebo in Type 2 Diabetes Mellitus, sponsored by MedImmune LLC. Completed at 1 site in Germany. Open to participants aged 18 Years to 74 Years. Per ClinicalTrials.gov, last updated 2020-06-05.

Sponsored by MedImmune LLC · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
20
Allocation
Randomized
Ages
18 Years to 74 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Type 2 Diabetes Mellitus

Keywords

  • MEDI0382, diabetes, obesity, overweight, type 2 diabetes mellitus
03

In context

Diabetes Mellitus

10,925 studies on the registry are indexed under Diabetes Mellitus; 1,319 are open to participants now.

This study's enrollment of 20 is below the median of 80 across 8,367 interventional studies indexed under Diabetes Mellitus.

Browse Diabetes Mellitus studies →

Lead sponsor

MedImmune LLC is the lead sponsor of 265 studies on the registry; none are open to participants now.

Of its 50 completed or terminated interventional studies of FDA-regulated products, 28 (56%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 74 Years
Sexes eligible
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

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
  5. Severe allergy/hypersensitivity to any of the proposed study treatments, standardized meals, or excipients.
  6. 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.
  7. 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.
  8. 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.

  9. 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
  10. Impaired renal function defined as estimated glomerular filtration rate (GFR) \< 60 mL/minute/1.73m\^2 at screening.

  11. Poorly controlled hypertension defined as:

    • Systolic blood pressure (BP) > 160 mm Hg
    • Diastolic BP or >= 90 mm Hg
  12. 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.
  13. Prolonged QT intervals corrected for heart rate or family history of long QT-segment at screening.
  14. PR (PQ) interval prolongation, intermittent second or third-degree atrioventricular (AV) block, or AV dissociation.
  15. Persistent or intermittent complete bundle branch block.
  16. 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.
  17. Severe congestive heart failure.
  18. Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia.
  19. Hemoglobinopathy, hemolytic anemia or chronic anemia or any other condition known to interfere with the interpretation of HbA1c measurement.
  20. 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.
  21. Any positive results for serum hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
  22. 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.
  23. Symptoms of depression or any other psychiatric disorder requiring treatment with medication.
  24. History of severe allergy/hypersensitivity, including to any component of the investigational product formulation or other biological agent, or ongoing clinically important allergy/hypersensitivity.
  25. Blood/plasma donation within 1 month of screening.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
20 participants (actual)

Study arms

  • 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

  • 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

  • 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

  • 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

Interventions

  • DrugMEDI0382

    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.

  • DrugPlacebo

    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.

06

What researchers measure

Primary outcomes

  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

    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)

  2. 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.

    Time frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

  3. 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.

    Time frame: Baseline (Day -1) through Day 56 (end of Up-titration period)

  4. 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.

    Time frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

  5. 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).

    Time frame: Baseline (Day -1) through Day 56 (end of Up-titration period)

  6. 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).

    Time frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

  7. 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.

    Time frame: Baseline (Day -1) through Day 56 (end of Up-titration period)

  8. 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.

    Time frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

  9. 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.

    Time frame: Baseline (Day -1) through Day 56 (end of Up-titration period)

  10. 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.

    Time frame: Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)

Secondary outcomes

  1. 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.

    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

  2. Maximum Observed Serum Concentration (Cmax) of MEDI0382

    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

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

    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

  4. 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.

    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

  5. 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.

    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

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

    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)

  7. 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.

    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)

  8. 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.

    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

  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

    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)

  10. 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.

    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

  11. 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).

    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)

  12. 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).

    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

  13. 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.

    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

  14. 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.

    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)

  15. Change From Baseline in HbA1c

    Change from baseline in HbA1c is reported.

    Time frame: Baseline (Day -1) through Day 77 (end of the treatment extension period)

  16. Absolute Change From Baseline in Body Weight

    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)

  17. Percentage Change From Baseline in Body Weight

    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)

  18. 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.

    Time frame: Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56

  19. 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.

    Time frame: Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56

  20. 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.

    Time frame: Baseline (Day -1) through Day 77 (end of the treatment extension period)

07

Results

Posted Jun 5, 2020

Participant flow

The study was conducted in Germany between 07Jan2019 and 28May2019.

Participant flow — Overall Study
MilestonePlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Started2639
Completed2537
Not completed0102
Withdrew: Withdrawal by subject0001
Withdrew: Not-specifed0101

Outcome measures

PrimaryNumber 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.

Time frame:
Baseline (Day -1) through Day 56 (end of Up-titration period)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) Through the End of the Up-titration Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
TEAEs2638
TESAEs0000
PrimaryNumber 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.

Time frame:
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Reported as:
Count of participants · Participants
Number of Participants With TEAEs and TESAEs Through the End of the Follow-up Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
TEAEs2638
TESAEs0000
PrimaryNumber 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.

Time frame:
Baseline (Day -1) through Day 56 (end of Up-titration period)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs Through the End of the Up-titration Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Atrial fibrillation0001
Supraventricular extrasystoles0001
Ventricular extrasystoles0001
Ventricular tachycardia1000
PrimaryNumber 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.

Time frame:
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal ECGs Reported as TEAEs Through the End of the Follow-up Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Atrial fibrillation0001
Supraventricular extrasystoles0001
Ventricular extrasystoles0001
Ventricular tachycardia1000
PrimaryNumber 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).

Time frame:
Baseline (Day -1) through Day 56 (end of Up-titration period)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Up-titration Period0100
PrimaryNumber 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).

Time frame:
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Number of Participants With Abnormal Vital Signs Reported as TEAEs Through the End of the Follow-up Period0100
PrimaryNumber 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.

Time frame:
Baseline (Day -1) through Day 56 (end of Up-titration period)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Up-titration Period0304
PrimaryNumber 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.

Time frame:
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Number of Participants With Abnormal Physical Examinations Reported as TEAEs Through the End of the Follow-up Period0304
PrimaryNumber 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.

Time frame:
Baseline (Day -1) through Day 56 (end of Up-titration period)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Up-titration Period0100
PrimaryNumber 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.

Time frame:
Baseline (Day-1) through 28 days post last dose (end of follow-up period; approximately up to 5 months)
Reported as:
Count of participants · Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Through the End of the Follow-up Period0100
SecondaryArea 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.

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
Reported as:
Geometric mean · ng.hr/mL
Area Under the Plasma Concentration Time Curve Over a Dosing Interval (AUCτ) of MEDI0382
ng.hr/mLMEDI0382 (Cohort 1 + Cohort 2)
Day 120.9 (15.9 to 29.0)
Day 723.7 (17.2 to 41.3)
Day 1459.9 (35.8 to 101)
Day 35276 (183 to 694)
Day 42332 (247 to 735)
Day 49434 (308 to 752)
Day 56611 (343 to 2840)
Day 84661 (372 to 4740)
SecondaryMaximum Observed Serum Concentration (Cmax) of MEDI0382

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
Reported as:
Geometric mean · ng/mL
Maximum Observed Serum Concentration (Cmax) of MEDI0382
ng/mLMEDI0382 (Cohort 1 + Cohort 2)
Day 11.02 (0.447 to 1.84)
Day 71.35 (0.934 to 2.51)
Day 143.43 (2.02 to 6.37)
Day 3515.3 (9.74 to 36.1)
Day 4217.8 (12.7 to 37.8)
Day 4924.9 (15.2 to 39.0)
Day 5632.8 (17.7 to 137)
Day 8435.3 (19.7 to 202)
SecondaryTime to Observed Maximum Serum Concentration (Tmax) of MEDI0382

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
Reported as:
Median · hours
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382
hoursMEDI0382 (Cohort 1 + Cohort 2)
Day 16.02 (4.00 to 8.00)
Day 76.00 (4.00 to 8.00)
Day 146.00 (4.00 to 8.00)
Day 356.00 (4.00 to 8.00)
Day 426.00 (2.00 to 8.00)
Day 496.00 (4.00 to 8.00)
Day 566.00 (4.00 to 8.00)
Day 846.00 (0.00 to 8.00)
SecondaryTrough 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.

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
Reported as:
Geometric mean · ng/mL
Trough Plasma Concentration (Ctrough) of MEDI0382
ng/mLMEDI0382 (Cohort 1 + Cohort 2)
Day 70.551 (0.401 to 0.775)
Day 141.46 (0.617 to 2.56)
Day 222.01 (1.09 to 3.27)
Day 294.65 (2.10 to 27.0)
Day 356.92 (3.85 to 23.2)
Day 428.85 (5.09 to 26.4)
Day 4911.0 (5.86 to 23.7)
Day 5616.3 (9.70 to 131)
Day 7013.6 (8.22 to 29.5)
Day 8418.8 (7.99 to 178)
SecondaryObserved 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.

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
Reported as:
Geometric mean · Ratio
Observed Accumulation Ratio (Ro) of MEDI0382 Calculated Using AUC
RatioMEDI0382 (Cohort 1 + Cohort 2)
Day 1NA (NA to NA)
Day 71.25 (1.09 to 1.65)
Day 141.40 (1.22 to 1.72)
Day 351.01 (0.761 to 1.81)
Day 420.857 (0.503 to 1.44)
Day 490.904 (0.603 to 1.18)
Day 561.16 (0.691 to 5.32)
Day 841.30 (0.526 to 8.89)
SecondaryNumber of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment

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)
Reported as:
Count of participants · Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382 Treatment
ParticipantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Positive at baseline0001
Positive post-baseline0304
Positive at baseline and post-baseline0001
Not detected at baseline; positive post-baseline0303
Positive at baseline; not detected post-baseline0001
SecondaryChange 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.

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)
Reported as:
Mean · mg/dL
Change From Baseline in Daily (24 Hours) Average Glucose Levels Over Time as Measured by Continuous Glucose Monitoring (CGM)
mg/dLPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
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 ± 29.2820.28 ± 33.40-13.03 ± 24.54
SecondaryChange 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.

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
Reported as:
Mean · mg/dL
Change From Baseline in 7-day Average Glucose Levels Over Time as Measured by CGM
mg/dLPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Days 1-737.53 ± NA-34.64 ± 15.48-3.96 ± 3.30-26.06 ± 9.47
Days 8-1422.73 ± NA-52.07 ± 19.14-14.44 ± 9.33-39.86 ± 10.44
Days 15-2113.83 ± NA-44.84 ± 22.06-13.72 ± 18.47-38.10 ± 16.50
Days 22-2812.54 ± NA-53.38 ± 29.905.88 ± 7.54-25.10 ± 33.72
Days 29-3516.11 ± NA-63.28 ± 22.230.32 ± 13.60-40.83 ± 20.31
Days 36-4222.29 ± NA-47.97 ± 24.65-20.03 ± 7.97-35.45 ± 26.96
Days 43-495.69 ± NA-48.06 ± 19.98-19.88 ± 29.62-46.84 ± 20.92
Days 50-562.02 ± NA-55.21 ± 22.32-19.59 ± 21.63-37.89 ± 18.28
Days 71-7721.50 ± NA-62.66 ± 28.88-19.06 ± 23.43-40.20 ± 31.70
SecondaryPercentage 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.

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)
Reported as:
Mean · Percent change in Glucose AUC4Hrs
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
Percent change in Glucose AUC4HrsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
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 ± 10.320.32 ± 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
SecondaryChange 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.

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
Reported as:
Mean · Percent of CV
Change From Baseline in Coefficient of Variation (CV) in Glucose Over 7 Days as Measured by CGM
Percent of CVPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Days 1 - 7-4.48 ± NA-0.96 ± 4.991.51 ± 3.84-2.41 ± 3.60
Days 8 - 14-3.67 ± NA-2.97 ± 4.342.26 ± 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 - 420.93 ± NA-4.96 ± 6.541.39 ± 1.69-1.38 ± 4.68
Days 43 - 49-3.96 ± NA-3.68 ± 5.422.18 ± 5.40-1.98 ± 3.48
Days 50 - 56-2.97 ± NA-2.94 ± 4.614.10 ± 2.60-2.36 ± 3.23
Days 71 - 77-4.91 ± NA-2.15 ± 4.882.60 ± 2.21-0.82 ± 3.73
SecondaryChange 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).

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)
Reported as:
Mean · Percentage of time spent
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 24 Hours Time as Measured by CGM
Percentage of time spentPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
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 ± 13.3810.42 ± 16.04-22.92 ± 30.64
Day 28 - Hyperglycemia-9.90 ± 18.41-33.54 ± 28.1213.19 ± 33.09-21.88 ± 25.20
Day 35 - Hyperglycemia-6.01 ± 6.84-51.24 ± 8.802.49 ± 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 - Hyperglycemia9.90 ± 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 - Normoglycemia19.27 ± 31.6739.58 ± 13.797.64 ± 15.3622.66 ± 18.04
Day 14 - Normoglycemia5.21 ± 11.7941.25 ± 10.2513.89 ± 29.4725.78 ± 24.35
Day 21 - Normoglycemia3.13 ± 8.8439.06 ± 14.23-11.11 ± 16.8419.53 ± 30.77
Day 28 - Normoglycemia9.90 ± 18.4120.21 ± 18.69-13.54 ± 34.3421.13 ± 25.07
Day 35 - Normoglycemia5.48 ± 7.6039.35 ± 10.46-2.14 ± 26.2927.81 ± 27.30
Day 42 - Normoglycemia19.79 ± 7.3734.58 ± 26.7816.67 ± 37.8036.72 ± 27.45
Day 49 - Normoglycemia-10.42 ± 20.6247.92 ± 5.464.86 ± 37.8141.82 ± 28.31
Day 56 - Normoglycemia19.79 ± 4.4240.42 ± 24.7817.31 ± 27.4730.51 ± 29.37
Day 77 - Normoglycemia18.75 ± 14.7343.13 ± 19.7221.88 ± 29.0427.73 ± 36.31
Day 7 - Hypoglycemia0.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00
Day 14 - Hypoglycemia0.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00
Day 21 - Hypoglycemia0.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00
Day 28 - Hypoglycemia0.00 ± 0.001.04 ± 2.330.00 ± 0.000.00 ± 0.00
Day 35 - Hypoglycemia0.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00
Day 42 - Hypoglycemia0.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00
Day 49 - Hypoglycemia0.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00
Day 56 - Hypoglycemia0.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00
Day 77 - Hypoglycemia0.00 ± 0.000.83 ± 1.860.00 ± 0.001.73 ± 3.73
SecondaryChange 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).

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
Reported as:
Mean · Percentage of time spent
Change From Baseline in Percentage of Time Spent in Hyperglycemia, Normoglycemia, and Clinically Significant Hypoglycemia Over 7 Days as Measured by CGM
Percentage of time spentPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
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 ± 29.126.55 ± 12.31-26.31 ± 25.76
Days 29 - 35 (Hyperglycemia)20.10 ± NA-51.69 ± 17.494.03 ± 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 ± NA32.58 ± 11.489.10 ± 5.9923.34 ± 15.55
Days 8 - 14 Normoglycemia)-16.47 ± NA43.41 ± 11.6517.07 ± 10.8533.32 ± 20.61
Days 15 - 21 (Normoglycemia)-19.20 ± NA40.36 ± 19.149.30 ± 15.0831.82 ± 27.12
Days 22 - 28 (Normoglycemia)-12.10 ± NA32.09 ± 24.74-6.27 ± 12.5822.44 ± 26.08
Days 29 - 35 (Normoglycemia)-19.49 ± NA42.95 ± 16.13-3.71 ± 15.8136.13 ± 30.86
Days 36 - 42 (Normoglycemia)-11.31 ± NA40.62 ± 24.5117.15 ± 8.7537.45 ± 29.72
Days 43 - 49 (Normoglycemia)-8.63 ± NA40.85 ± 17.9314.07 ± 19.0242.81 ± 30.11
Days 50 - 56 (Normoglycemia)-6.37 ± NA44.10 ± 19.7418.10 ± 14.9433.61 ± 27.62
Days 71 - 77 (Normoglycemia)-18.27 ± NA46.39 ± 29.9915.08 ± 17.4737.93 ± 38.28
Days 1 - 7 (Hypoglycemia)0.00 ± NA0.00 ± 0.000.00 ± 0.000.00 ± 0.00
Days 8 - 14 (Hypoglycemia)0.00 ± NA1.20 ± 1.680.00 ± 0.000.28 ± 0.68
Days 15 - 21 (Hypoglycemia)0.00 ± NA0.00 ± 0.000.00 ± 0.000.20 ± 0.49
Days 22 - 28 Hypoglycemia)0.00 ± NA1.09 ± 2.280.00 ± 0.000.79 ± 1.76
Days 29 - 35 (Hypoglycemia)0.00 ± NA0.27 ± 0.610.00 ± 0.000.00 ± 0.00
Days 36 - 42 (Hypoglycemia)0.00 ± NA0.00 ± 0.000.00 ± 0.000.00 ± 0.00
Days 43 - 49 (Hypoglycemia)0.00 ± NA0.09 ± 0.200.40 ± 0.700.15 ± 0.37
Days 50 - 56 (Hypoglycemia)0.00 ± NA0.06 ± 0.140.20 ± 0.350.15 ± 0.37
Days 71 - 77 (Hypoglycemia)0.00 ± NA2.16 ± 3.230.15 ± 0.260.44 ± 0.59
SecondaryChange 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.

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
Reported as:
Mean · Percent of HbA1C
Change From Baseline in Estimated Hemoglobin A1c (HbA1c) Based on 7-day CGM Glucose Over Time
Percent of HbA1CPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Days 1 - 71.31 ± NA-1.21 ± 0.54-0.14 ± 0.12-0.91 ± 0.33
Days 8 - 140.79 ± NA-1.81 ± 0.67-0.50 ± 0.33-1.39 ± 0.36
Days 15 - 210.48 ± NA-1.56 ± 0.77-0.48 ± 0.64-1.33 ± 0.58
Days 22 - 280.44 ± NA-1.86 ± 1.040.21 ± 0.26-0.88 ± 1.18
Days 29 - 350.56 ± NA-2.21 ± 0.780.01 ± 0.47-1.42 ± 0.71
Days 36 - 420.78 ± NA-1.67 ± 0.86-0.70 ± 0.28-1.24 ± 0.94
Days 43 - 490.20 ± NA-1.68 ± 0.70-0.69 ± 1.03-1.63 ± 0.73
Days 50 - 560.07 ± NA-1.92 ± 0.78-0.68 ± 0.75-1.32 ± 0.64
Days 71 - 770.75 ± NA-2.18 ± 1.01-0.66 ± 0.82-1.40 ± 1.10
SecondaryChange 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.

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)
Reported as:
Mean · mg/dL
Change From Baseline in Fasting Plasma Glucose Over Time
mg/dLPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Day 79.0 ± 48.1-32.0 ± 17.713.7 ± 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 3528.5 ± 16.3-46.8 ± 25.85.7 ± 29.2-44.4 ± 15.8
Day 429.0 ± 14.1-42.6 ± 24.52.0 ± 27.9-35.1 ± 24.6
Day 4923.5 ± 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 771.0 ± 21.2-47.6 ± 34.2-9.7 ± 32.9-28.6 ± 20.5
SecondaryChange From Baseline in HbA1c

Change from baseline in HbA1c is reported.

Time frame:
Baseline (Day -1) through Day 77 (end of the treatment extension period)
Reported as:
Mean · Percent of HbA1C
Change From Baseline in HbA1c
Percent of HbA1CPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Change From Baseline in HbA1c0.10 ± 0.00-1.44 ± 0.52-0.40 ± 0.35-0.59 ± 0.74
SecondaryAbsolute Change From Baseline in Body Weight

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)
Reported as:
Mean · Kg
Absolute Change From Baseline in Body Weight
KgPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
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
SecondaryPercentage Change From Baseline in Body Weight

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)
Reported as:
Mean · Percentage change in body weight
Percentage Change From Baseline in Body Weight
Percentage change in body weightPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
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
SecondaryAbsolute 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.

Time frame:
Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56
Reported as:
Mean · Kg
Absolute Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period
KgPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Day 7-2.05 ± 1.06-1.78 ± 0.86-0.70 ± 1.640.49 ± 4.87
Day 14-1.95 ± 0.35-2.72 ± 0.68-0.73 ± 1.100.08 ± 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 490.10 ± 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
SecondaryPercentage 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.

Time frame:
Baseline (Day -1), Days 7, 14, 35, 42, 49, and 56
Reported as:
Mean · Percentage change in body weight
Percentage Change From Baseline in Body Weight to the End of Each Week of the Up-titration Period
Percentage change in body weightPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Day 7-2.22 ± 1.09-1.83 ± 0.95-0.77 ± 1.960.67 ± 5.69
Day 14-2.13 ± 0.32-2.76 ± 0.62-0.83 ± 1.300.22 ± 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 490.11 ± 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
SecondaryPercentage 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.

Time frame:
Baseline (Day -1) through Day 77 (end of the treatment extension period)
Reported as:
Number · Percentage of participants
Percentage of Participants Achieving Greater Than 5% Body Weight Loss From Baseline to the End of the Treatment Extension Period
Percentage of participantsPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
Day 70000
Day 140000
Day 35040025
Day 42040025
Day 49060050
Day 56050028.6
Day 77080071.4

Adverse events

Collected over Baseline (Day -1) through 28 days post last dose (approximately up to 5 months). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo Cohort 10/2 (0%)0/2 (0%)2/2 (100%)
MEDI0382 Cohort 10/6 (0%)0/6 (0%)6/6 (100%)
Placebo Cohort 20/3 (0%)0/3 (0%)3/3 (100%)
MEDI0382 Cohort 20/9 (0%)0/9 (0%)8/9 (88.9%)
Most frequent other events
Showing 10 of 32
Most frequent other events
EventPlacebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2
ConstipationGastrointestinal disorders0/24/61/32/9
NasopharyngitisInfections and infestations1/22/62/31/9
Appetite disorderMetabolism and nutrition disorders0/24/60/30/9
Ventricular tachycardiaCardiac disorders1/20/60/30/9
Abdominal distensionGastrointestinal disorders1/21/61/32/9
DyspepsiaGastrointestinal disorders0/20/61/34/9
Early satietyGeneral disorders0/20/60/34/9
Injection site reactionGeneral disorders0/22/60/34/9
Abdominal pain upperGastrointestinal disorders0/20/61/30/9
DiarrhoeaGastrointestinal disorders0/22/60/33/9

Baseline characteristics

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

Age, Continuous
Age, Continuous(Years)Placebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2Total
Mean68.5 ± 3.565.3 ± 6.262.3 ± 3.567.1 ± 5.366.0 ± 5.2
Sex: Female, Male
Sex: Female, Male(Participants)Placebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2Total
Female01225
Male251715
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Placebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2Total
Hispanic or Latino00000
Not Hispanic or Latino263920
Unknown or Not Reported00000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Placebo Cohort 1MEDI0382 Cohort 1Placebo Cohort 2MEDI0382 Cohort 2Total
American Indian or Alaska Native00000
Asian00000
Native Hawaiian or Other Pacific Islander00000
Black or African American00000
White263920
More than one race00000
Unknown or Not Reported00000
08

Study locations

1 site
  • Research Site
    Neuss, 41460, Germany
09

References and documents

Study documents

  • Study protocol · Apr 16, 2019
  • Statistical analysis plan · Jan 22, 2019

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 5, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03745937
Lead sponsor
MedImmune LLC
Responsible party
Sponsor
First posted
Nov 19, 2018
Start date
Jan 7, 2019
Primary completion
May 28, 2019
Completion
May 28, 2019
Results posted
Jun 5, 2020
Last update
Jun 5, 2020

Study contacts

Tim Heise, MD
principal investigator · Profil Institut für Stoffwechselforschung GmbH

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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