CompletedNCT02548585Updated Apr 5, 2019Results posted

A Multiple-ascending-dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus

A Phase 1/2 interventional study of MEDI0382 and Placebo in Type 2 Diabetes Mellitus, sponsored by MedImmune LLC. Completed at 11 sites in Germany. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2019-04-05.

Sponsored by MedImmune LLC · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 113
Allocation: Randomized
Ages: 18 Years to 65 Years
Sex: All

Study summary

A Phase 1/2, multiple dose study with 6 cohorts of ascending doses designed to evaluate the efficacy, safety and pharmacokinetics (PK) of MEDI0382 in participants with Type 2 Diabetes Mellitus (T2DM).

Read the detailed description

This is a randomized, double-blind, placebo controlled study designed to evaluate the efficacy, safety, and PK of MEDI0382 administered as multiple daily SC doses to participants with T2DM. Approximately one hundred and seven participants will be enrolled across 6 cohorts. In cohorts 1-3 the participants will be randomized to MEDI0382 or placebo (2:1). In Cohort 4, participants will be randomized to MEDI0382 or placebo (1:1). In cohort 5 and 6 participants will be randomized to MEDI0382 or placebo (3:1).

Conditions studied

Type 2 Diabetes Mellitus

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Keywords

MEDI0382, diabetes

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 113 is above 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.

Who can participate

Ages eligible: 18 Years to 65 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Diagnosis of T2DM
Must provide written informed consent
Body mass index greater than (>) 27 and less than (\<) 40 kg/m\^2, inclusive
Venous access suitable for multiple cannulations
Vital signs within normal specified ranges
Females must be non-lactating and non-childbearing potential
Males must practice 2 effective contraceptive measures if sexually active

Exclusion criteria

Exclusion Criteria:

Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
History of cancer within the last 10 years, with the exception of non-melanoma skin cancer
Any clinically important illness (except for T2DM), medical/surgical procedure, or trauma within 4 weeks prior to dosing
Fasting glucose greater than or equal to (>=) 200 mg/dL
Positive Hepatitis B, Hepatitis C or human immunodeficiency virus test or use of antiretroviral medications at screening.
Concurrent or previous use of a glucagon-like peptide 1 receptor agonist
Current or previous use of systemic corticosteroids within the past 28 days prior to screening
Use of any medicinal products or herbal preparations licensed for control of body weight or appetite is prohibited.
Known or suspected history of alcohol or drug abuse within the past 3 years.
Positive drug screen

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment: 113 participants (actual)

Study arms

Placebo comparator
Placebo
Participants will receive placebo (matched to either 100 micrograms \[mcg\], or 150 mcg or 200 mcg or 300 mcg of MEDI0382) subcutaneously (SC) once daily from Day 1 to Day 7 (Cohort 1); or Day 1 to Day 11 (Cohort 2); or Day 1 to Day 15 (Cohort 3); or Day 1 to Day 41 (Cohort 4); or Day 1 to Day 22 (Cohort 5); or Day 1 to Day 17 (Cohort 6).
Drug: Placebo
Experimental
Cohort 1: MEDI0382 100 mcg
Participants will receive MEDI0382 100 mcg SC once daily from Day 1 to Day 7.
Drug: MEDI0382
Experimental
Cohort 2: MEDI0382 150 mcg
Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4) and thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 7 days (Day 5 to Day 11).
Drug: MEDI0382
Experimental
Cohort 3: MEDI0382 200 mcg
Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 7 days (Day 9 to Day 15).
Drug: MEDI0382
Experimental
Cohort 4: MEDI0382 200 mcg
Participants will receive MEDI0382 100 mcg SC once daily for at least 4 days (Day 1 to Day 4); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 4 days (Day 5 to Day 8); followed by second up titrated dose of MEDI0382 200 mcg SC once daily for 4 days (Day 9 to Day 12), then a further MEDI0382 200 mcg SC once daily for 28 days (Day 13 to Day 40) at home-dosing; followed by MEDI0382 200 mcg SC once daily for 1 day in hospital (Day 41).
Drug: MEDI0382
Experimental
Cohort 5: MEDI0382 300 mcg
Participants will receive MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 150 mcg SC once daily for 5 days (Day 6 to Day 10); then a second up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 11 to Day 15); followed by third up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 16 to Day 22).
Drug: MEDI0382
Experimental
Cohort 6: MEDI0382 300 mcg
Participants will receive MEDI0382 100 mcg SC once daily for at least 5 days (Day 1 to Day 5); thereafter, an up titrated dose of MEDI0382 200 mcg SC once daily for 5 days (Day 6 to Day 10); followed by a second up titrated dose of MEDI0382 300 mcg SC once daily for 7 days (Day 11 to Day 17).
Drug: MEDI0382

Interventions

DrugMEDI0382
MEDI0382 administered subcutaneously.
DrugPlacebo
Placebo administered subcutaneously.

What researchers measure

Primary outcomes

Percent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4)
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hours (hrs) after consumption of the standardized meal (with no additional food intake during this time).
Time frame: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post standardized meal intake (SMI) on Baseline (Day -1) and EOT (Day 41)
Change From Baseline in Body Weight to the EOT (Cohort 4)
Time frame: Baseline (Day 1) and EOT (Day 42)

Secondary outcomes

Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6)
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time frame: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 22 for Cohort 5; and Day 17 for Cohort 6)
Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6)
Time frame: Cohort 1: Baseline (Day 1) to EOT (Day 8); Cohort 2: Baseline (Day 1) to EOT (Day 12); Cohort 3: Baseline (Day 1) to EOT (Day 16); Cohort 5: Baseline (Day 1) to EOT (Day 22); Cohort 6: Baseline (Day 1) to EOT (Day 17)
Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6)
Time frame: Cohort 4: Baseline (Day -2) to EOT (Day 42); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)
Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6)
Time frame: Cohort 4: Baseline (Day -2) to EOT (Day 41); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)
Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time frame: Cohort 1: Baseline (Day-1) to EOT (Day7); Cohort 2: Baseline (Day-1) to EOT (Day11); Cohort 3: Baseline (Day-1) to EOT (Day15); Cohort 4: Baseline (Day-1) to EOT (Day41); Cohort 5: Baseline (Day-1) to EOT (Day22); Cohort 6: Baseline (Day-1) to EOT (Day17)
Percent Change From Baseline in Glucose Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) After MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time frame: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, 240 minutes, and 24 hrs post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. Serious adverse events (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days).
Time frame: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs
TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to vital signs and physical examination abnormalities were reported.
Time frame: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs
TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to ECG abnormalities were reported.
Time frame: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs
TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to laboratory abnormalities were reported.
Time frame: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6)
The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal ideation were reported below.
Time frame: Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days)
Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6)
The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal behaviour were reported below.
Time frame: Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days)
Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3)
Terminal elimination half Life is the time measured for the plasma concentration of MEDI0382 to decrease by one half.
Time frame: Cohort (C) 1 (Day [D] 1 and [&] D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose
Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3)
Accumulation ratio was calculated as, Rac obtained from area under the curve from time zero to end of dosing interval (AUC\[0-tau\]) of Nth day divided by AUC(0-tau) of Day 1.
Time frame: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose
Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Time frame: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Time frame: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Time frame: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Time frame: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Time frame: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Time frame: Day 1 up to 7-14 days post-last dose of MEDI0382 for all cohorts (Approximately 60 days)
Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6)
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time frame: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)
Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time frame: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)
Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)
Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).
Time frame: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)
Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)
Mixes-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). Incretins included glucagon-like peptide-1 (GLP-1; active and inactive both), glucagon, and gastric inhibitory peptide (GIP).
Time frame: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)

Results

Posted Apr 5, 2019

Participant flow

The study was conducted from 09 Dec 2015 to 24 Feb 2017 in Germany.

Participant flow — Overall Study
Milestone	Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg
Started	45	6	6	7	25	12	12
Treated	45	6	6	7	25	11	12
Completed	43	6	6	5	22	10	11
Not completed	2	0	0	2	3	2	1
Withdrew: Withdrawal by subject	0	0	0	0	0	1	0
Withdrew: Lost to follow-up	1	0	0	0	0	0	0
Withdrew: Other	1	0	0	2	3	0	1
Withdrew: Randomized but not treated	0	0	0	0	0	1	0

Outcome measures

PrimaryPercent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4)

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hours (hrs) after consumption of the standardized meal (with no additional food intake during this time).

Time frame:: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post standardized meal intake (SMI) on Baseline (Day -1) and EOT (Day 41)
Reported as:: Mean · Percent change

Percent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4)
Percent change	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg
Percent Change From Baseline in Mixed-meal Test (MMT) Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours to the End of Treatment (EOT) (Cohort 4)	-9.24 ± 12.30	-33.81 ± 18.62

Statistical analysis

Cohort 4: Placebo vs Cohort 4: MEDI0382 200 mcg · ANCOVA · p = < 0.0001p-value was based on pairwise comparison using analysis of covariance (ANCOVA) adjusted by baseline value.

PrimaryChange From Baseline in Body Weight to the EOT (Cohort 4)

Time frame:: Baseline (Day 1) and EOT (Day 42)
Reported as:: Mean · Kilograms (Kg)

Change From Baseline in Body Weight to the EOT (Cohort 4)
Kilograms (Kg)	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg
Change From Baseline in Body Weight to the EOT (Cohort 4)	-1.71 ± 2.10	-3.83 ± 2.09

Statistical analysis

Cohort 4: Placebo vs Cohort 4: MEDI0382 200 mcg · ANCOVA · p = 0.0008p-value was based on pairwise comparison using ANCOVA adjusted by baseline value.

SecondaryPercent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6)

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Time frame:: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 22 for Cohort 5; and Day 17 for Cohort 6)
Reported as:: Mean · Percent change

Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6)
Percent change	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Percent Change From Baseline in MMT Glucose AUC0-4h to the EOT (Cohorts 1, 2, 3, 5, and 6)	-14.60 ± 5.56	-41.80 ± 11.07	-15.07 ± 13.46	-36.73 ± 10.09	-0.47 ± 15.16	-39.58 ± 5.27	-14.52 ± 8.12	-41.66 ± 9.97	-4.80 ± 3.45	-38.19 ± 12.51

SecondaryChange From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6)

Time frame:: Cohort 1: Baseline (Day 1) to EOT (Day 8); Cohort 2: Baseline (Day 1) to EOT (Day 12); Cohort 3: Baseline (Day 1) to EOT (Day 16); Cohort 5: Baseline (Day 1) to EOT (Day 22); Cohort 6: Baseline (Day 1) to EOT (Day 17)
Reported as:: Mean · Kg

Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6)
Kg	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Change From Baseline in Body Weight to the EOT (Cohorts 1, 2, 3, 5, and 6)	-1.20 ± 0.44	-2.32 ± 1.29	-1.00 ± 1.13	-1.52 ± 0.57	-2.90 ± 1.05	-4.63 ± 1.98	-0.98 ± 2.12	-3.26 ± 1.99	-0.94 ± 3.09	-2.04 ± 1.52

SecondaryPercent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6)

Time frame:: Cohort 4: Baseline (Day -2) to EOT (Day 42); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)
Reported as:: Mean · Percent change

Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6)
Percent change	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Percent Change From Baseline in Hemoglobin A1c (HbA1c) to the EOT (Cohorts 4, 5, and 6)	-0.58 ± 0.30	-0.92 ± 0.41	-0.10 ± 0.29	-0.55 ± 0.35	-0.18 ± 0.19	-0.42 ± 0.27

SecondaryChange From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6)

Time frame:: Cohort 4: Baseline (Day -2) to EOT (Day 41); Cohort 5: Baseline (Day -2) to EOT (Day 22); Cohort 6: Baseline (Day -2) to EOT (Day 17)
Reported as:: Mean · micromol/L

Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6)
micromol/L	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Change From Baseline in Fructosamine to the EOT (Cohorts 4, 5, and 6)	-33.7 ± 44.6	-67.9 ± 44.4	-27.8 ± 25.8	-47.4 ± 15.7	-48.8 ± 43.7	-47.5 ± 55.3

SecondaryChange From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Time frame:: Cohort 1: Baseline (Day-1) to EOT (Day7); Cohort 2: Baseline (Day-1) to EOT (Day11); Cohort 3: Baseline (Day-1) to EOT (Day15); Cohort 4: Baseline (Day-1) to EOT (Day41); Cohort 5: Baseline (Day-1) to EOT (Day22); Cohort 6: Baseline (Day-1) to EOT (Day17)
Reported as:: Mean · mg/dL

Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)
mg/dL	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Change From Baseline in Fasting Glucose Prior to MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)	-32.44 ± 17.19	-74.48 ± 24.59	-49.86 ± 23.24	-54.06 ± 19.51	-4.20 ± 33.73	-63.67 ± 11.93	-18.52 ± 18.88	-50.62 ± 33.61	-32.08 ± 17.49	-54.42 ± 19.75	-16.58 ± 12.45	-55.21 ± 31.13

SecondaryPercent Change From Baseline in Glucose Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) After MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Time frame:: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, 240 minutes, and 24 hrs post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)
Reported as:: Mean · Percent change

Percent Change From Baseline in Glucose Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) After MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)
Percent change	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Percent Change From Baseline in Glucose Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24h) After MMT to the EOT (Cohorts 1, 2, 3, 4, 5, and 6)	-21.80 ± 1.41	-28.34 ± 13.52	0.80 ± 39.55	-29.32 ± 17.24	-13.80 ± 15.95	-27.07 ± 10.82	-1.06 ± 11.47	-13.50 ± 18.19	-4.20 ± 28.58	-34.51 ± 11.25	-10.10 ± 14.69	-26.95 ± 9.45

SecondaryNumber of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)

An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. Serious adverse events (SAE) is any AE that resulted in death, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event. TEAEs and TESAEs are defined as AEs and SAEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days).

Time frame:: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Reported as:: Count of participants · Participants

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Participants	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
TEAEs	2	6	3	5	3	7	23	22	4	10	2	10
TESAEs	0	0	0	0	0	1	1	0	0	0	0	0

SecondaryNumber of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs

TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 28 days after the last study dose of each cohort (approximately 60 days). Number of participants with TEAEs related to vital signs and physical examination abnormalities were reported.

Time frame:: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Reported as:: Count of participants · Participants

Number of Participants With Abnormal Vital Signs and Physical Examination Reported as TEAEs
Participants	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Blood Pressure increased	2	1	0	0	0
Blood pressure systolic increased	0	0	1	1	0
Blood pressure diastolic increased	0	0	0	0	1
Physical Examinations	0	0	0	0	0

SecondaryNumber of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs

Time frame:: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Reported as:: Count of participants · Participants

Number of Participants With Abnormal 12 Lead Electrocardiogram (ECG) Reported as TEAEs
Participants	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg
Arrhythmia	0	1	0	0	0	0	0	0
Atrial fibrillation	0	0	0	0	0	0	0	1
Atrioventricular block first degree	0	1	0	0	0	0	0	0
Atrioventricular block second degree	0	1	0	0	0	0	0	0
Electrocardiogram ST segment depression	0	0	0	0	0	1	0	0
Extrasystoles	0	0	1	0	1	0	0	0
Sinus tachycardia	0	0	0	0	0	0	0	1
Supraventricular extrasystoles	0	0	0	0	0	0	1	0
Supraventricular tachycardia	1	1	1	0	1	1	0	0
Tachycardia	0	1	0	1	0	1	0	0
Ventricular extrasystoles	0	1	1	1	0	0	1	1
Ventricular tachycardia	0	0	0	0	1	1	0	0

SecondaryNumber of Participants With Abnormal Clinical Laboratory Reported as TEAEs

Time frame:: From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days])
Reported as:: Count of participants · Participants

Number of Participants With Abnormal Clinical Laboratory Reported as TEAEs
Participants	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg
Lipase increased	1	0	0	1	2	1
Hypokalemia	0	0	1	1	0	1
C-reactive protein increased	0	1	0	0	0	0
Hypoglycemia	0	0	0	1	0	0
Chromaturia	0	0	0	1	1	0

SecondaryNumber of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6)

The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behaviour of participants. Yes/No responses are mapped to C-SSRS to assess whether participant experienced suicidal behaviour and suicidal ideation. Suicidal behaviour questions includes preparatory acts or behaviour, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation questions includes wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act (without specific plan), and active suicidal ideation with specific plan and intent. Participants with yes response to any category for suicidal ideation were reported below.

Time frame:: Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days)
Reported as:: Count of participants · Participants

Number of Participants With Any Suicidal Ideation as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score (Cohorts 4, 5, and 6)
Participants	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Day -1	1	4	0	2	0	2
Day 13	1	0	—	—	—	—
Day 20	0	0	—	—	—	—
Day 27	0	0	—	—	—	—
Day 34	0	0	—	—	—	—
Day 40	0	0	—	—	—	—
Days 7-14 post last dose of MEDI0382	—	—	0	1	0	0

SecondaryNumber of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6)

Time frame:: Cohort 4: Day -1, and Days 13, 20, 27, 34, and 40; Cohort 5: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 36 days); Cohort 6: Day -1 and Day 7-14 post last dose of MEDI0382 (approximately 31 days)
Reported as:: Count of participants · Participants

Number of Participants With Any Suicidal Behaviour as Assessed by C-SSRS Score (Cohorts 4, 5, and 6)
Participants	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Day -1	2	2	0	1	0	1
Day 13	1	0	—	—	—	—
Day 20	0	0	—	—	—	—
Day 27	0	0	—	—	—	—
Day 34	0	0	—	—	—	—
Day 40	0	0	—	—	—	—
Days 7-14 post last dose of MEDI0382	—	—	0	0	0	0

SecondaryTerminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3)

Terminal elimination half Life is the time measured for the plasma concentration of MEDI0382 to decrease by one half.

Time frame:: Cohort (C) 1 (Day [D] 1 and [&] D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose
Reported as:: Geometric mean · hr

Terminal Elimination Half Life (t1/2) of MEDI0382 (Cohorts 1, 2, and 3)
hr	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg
Day 1	8.5 (NA to NA)	—	—
Day 5	—	10.3 (7.8 to 13.5)	—
Day 7	11.7 (5.5 to 25.1)	—	—
Day 9	—	—	8.3 (NA to NA)
Day 11	—	11.3 (5.9 to 21.7)	—
Day 15	—	—	11.3 (8.2 to 15.5)

SecondaryAccumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3)

Accumulation ratio was calculated as, Rac obtained from area under the curve from time zero to end of dosing interval (AUC\[0-tau\]) of Nth day divided by AUC(0-tau) of Day 1.

Time frame:: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose; and additional 48 hr post C1D7, C2D11, C3D15 dose
Reported as:: Geometric mean · Ratio

Accumulation Ratio (Rac) of MEDI0382 (Cohorts 1, 2, and 3)
Ratio	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg
Day 1	NA (NA to NA)	—	—
Day 5	—	NA (NA to NA)	—
Day 7	1.3 (1.1 to 1.5)	—	—
Day 9	—	—	NA (NA to NA)
Day 11	—	1.1 (0.9 to 1.8)	—
Day 15	—	—	1.3 (1.1 to 1.5)

SecondaryArea Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)

Time frame:: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Reported as:: Geometric mean · ng*hr/mL

Area Under the Concentration Time Curve From Time Zero to End of Dosing Interval (AUC[0-tau]) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
ng*hr/mL	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg
Day 1	82.21 (44.56 to 151.69)	—	—	—	—	—
Day 5	—	174.58 (87.41 to 348.67)	—	—	—	—
Day 7	107.01 (54.10 to 211.64)	—	—	—	—	—
Day 9	—	—	194.78 (146.17 to 259.56)	164.05 (42.67 to 630.76)	—	—
Day 11	—	157.31 (82.45 to 421.12)	—	—	—	275.29 (169.33 to 447.48)
Day 15	—	—	195.40 (89.8 to 425.17)	—	—	—
Day 16	—	—	—	—	261.90 (166.58 to 411.74)	—
Day 17	—	—	—	—	—	246.06 (130.34 to 464.51)
Day 22	—	—	—	—	254.35 (196.10 to 329.9)	—
Day 41	—	—	—	199.10 (84.57 to 468.75)	—	—

SecondaryArea Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)

Time frame:: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Reported as:: Geometric mean · ng*hr/mL

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - Inf)] of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
ng*hr/mL	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg
Day 1	103.46 (NA to NA)	—	—	—	—	—
Day 5	—	207.15 (11.98 to 3580.41)	—	—	—	—
Day 7	184.68 (107.76 to 316.51)	—	—	—	—	—
Day 9	—	—	242.60 (NA to NA)	238.22 (80.99 to 700.67)	—	—
Day 11	—	215.80 (112.90 to 412.47)	—	—	—	—
Day 15	—	—	271.84 (119.33 to 619.24)	—	—	—
Day 16	—	—	—	—	317.93 (182.24 to 554.64)	—
Day 17	—	—	—	—	—	327.28 (249.98 to 428.49)
Day 22	—	—	—	—	294.60 (172.52 to 503.05)	—
Day 41	—	—	—	262.17 (99.79 to 688.77)	—	—

SecondaryMaximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)

Time frame:: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Reported as:: Geometric mean · ng/mL

Maximum Observed Plasma Concentration (Cmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
ng/mL	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg
Day 1	4.97 (0.33 to 7.41)	—	—	—	—	—
Day 5	—	9.66 (4.68 to 19.95)	—	—	—	—
Day 7	6.26 (3.36 to 11.67)	—	—	—	—	—
Day 9	—	—	10.57 (6.33 to 17.66)	11.64 (3.16 to 42.94)	—	—
Day 11	—	9.57 (4.63 to 19.79)	—	—	—	13.69 (5.73 to 32.71)
Day 15	—	—	10.97 (4.62 to 26.06)	—	—	—
Day 16	—	—	—	—	17.65 (8.82 to 35.29)	—
Day 17	—	—	—	—	—	15.55 (7.55 to 32.01)
Day 22	—	—	—	—	15.77 (10.02 to 24.8)	—
Day 41	—	—	—	13.42 (4.77 to 37.75)	—	—

SecondaryMinimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)

Time frame:: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Reported as:: Geometric mean · ng/mL

Minimum Observed Plasma Concentration (Cmin) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
ng/mL	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg
Day 1	0.705 (0.33 to 1.49)	—	—	—	—	—
Day 5	—	2.685 (1.06 to 6.79)	—	—	—	—
Day 7	2.372 (1.18 to 4.78)	—	—	—	—	—
Day 9	—	—	3.521 (2.16 to 5.75)	2.635 (0.79 to 8.83)	—	—
Day 11	—	3.59 (1.62 to 7.94)	—	—	—	3.586 (1.45 to 8.88)
Day 15	—	—	4.973 (2.24 to 11.05)	—	—	—
Day 16	—	—	—	—	4.062 (1.68 to 9.84)	—
Day 17	—	—	—	—	—	4.766 (2.74 to 8.3)
Day 22	—	—	—	—	5.21 (1.97 to 13.81)	—
Day 41	—	—	—	3.38 (1.03 to 11.04)	—	—

SecondaryTime to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)

Time frame:: C1 (D1 & D7), C2 (D5 & D11), and C3 (D9 & D15): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose and additional 48 hr post dose for C1D7, C2D11, C3D15; C4 (D9 & D41), C5 (D16 & D22), and C6 (D11 & D17): pre-dose & 0.5, 1, 2, 4, 6, 8, 12, 24 hr post dose
Reported as:: Median · hr

Time to Reach Maximum Observed Plasma Concentration (Tmax) of MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
hr	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg
Day 1	8 (6 to 8)	—	—	—	—	—
Day 5	—	6 (4 to 8)	—	—	—	—
Day 7	6 (4 to 6)	—	—	—	—	—
Day 9	—	—	6 (6 to 8)	4 (1 to 6)	—	—
Day 11	—	6 (4 to 6)	—	—	—	6 (4 to 12)
Day 15	—	—	6 (4 to 8)	—	—	—
Day 16	—	—	—	—	4 (2 to 8)	—
Day 17	—	—	—	—	—	4 (2 to 6)
Day 22	—	—	—	—	4 (4 to 8)	—
Day 41	—	—	—	4 (4 to 8)	—	—

SecondaryNumber of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)

Time frame:: Day 1 up to 7-14 days post-last dose of MEDI0382 for all cohorts (Approximately 60 days)
Reported as:: Count of participants · Participants

Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)
Participants	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Number of Participants With Positive Anti-drug Antibodies to MEDI0382 (Cohorts 1, 2, 3, 4, 5, and 6)	0	0	1	0	0	0	0	0	0	0	0	0

SecondaryPercent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6)

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Time frame:: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4; Day 22 for Cohort 5; and Day 17 for Cohort 6)
Reported as:: Mean · Percent change

Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6)
Percent change	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Percent Change From Baseline in Insulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, 4, 5, and 6)	10.83 ± 21.33	-9.37 ± 29.17	-3.67 ± 13.76	36.32 ± 35.21	-20.43 ± 68.82	-17.47 ± 38.84	-8.63 ± 32.33	-1.17 ± 44.20	-17.70 ± 16.47	1.01 ± 31.00	-8.18 ± 28.34	-7.72 ± 37.03

SecondaryPercent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Time frame:: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)
Reported as:: Mean · Percent change

Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)
Percent change	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg
Percent Change From Baseline in Proinsulin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)	-3.27 ± 38.92	-52.10 ± 36.29	-33.13 ± 40.07	-36.77 ± 19.62	81.27 ± 77.21	-54.13 ± 26.40	-29.72 ± 31.13	-47.93 ± 22.12

SecondaryPercent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)

Mixed-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time).

Time frame:: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)
Reported as:: Mean · Percent change

Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)
Percent change	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg
Percent Change From Baseline in C-peptide AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)	10.17 ± 5.05	-3.82 ± 21.29	-1.43 ± 6.02	39.78 ± 32.88	79.37 ± 91.56	-9.07 ± 27.27	8.08 ± 32.12	15.66 ± 42.35

SecondaryPercent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)

Mixes-meal test involved consumption of a standardized meal (nutritional supplement containing the components of fat, carbohydrate and protein, which make up a standard MMT) within 5 minutes, and timed serial blood samples were obtained for measurement of glucose and parameters related to glucose metabolism just before and 4 hrs after consumption of the standardized meal (with no additional food intake during this time). Incretins included glucagon-like peptide-1 (GLP-1; active and inactive both), glucagon, and gastric inhibitory peptide (GIP).

Time frame:: 0 minutes before; and 15, 30, 45, 60, 90, 120, 180, and 240 minutes post SMI on Baseline (Day -1) and EOT (Day 7 for Cohort 1; Day 11 for Cohort 2; Day 15 for Cohort 3; Day 41 for Cohort 4)
Reported as:: Mean · Percent change

Percent Change From Baseline in Incretin AUC0-4h After MMT to EOT (Cohorts 1, 2, 3, and 4)
Percent change	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg
GLP-1, Active: Change at EOT	8.30 ± 13.15	-33.67 ± 16.84	-10.40 ± 10.47	-50.45 ± 12.30	-2.87 ± 20.32	-40.36 ± 26.90	1.63 ± 26.43	-49.73 ± 22.88
GLP-1, Inactive: Change at EOT	-20.30 ± NA	0.70 ± NA	-22.90 ± NA	-10.93 ± 22.36	1.75 ± 29.20	-8.07 ± 11.30	3.99 ± 29.59	-28.85 ± 16.73
Glucagon: Change at EOT	-13.85 ± 18.60	-20.25 ± 25.45	-17.53 ± 19.46	-38.12 ± 16.33	-18.73 ± 21.59	-3.05 ± 36.56	-1.76 ± 21.47	-30.17 ± 25.56
GIP: Change at EOT	18.00 ± 2.83	-46.50 ± 14.85	4.10 ± 24.61	-27.08 ± 25.03	-6.30 ± 7.35	-21.34 ± 39.48	-6.60 ± 19.43	-37.38 ± 23.14

Adverse events

Collected over From Day 1 to follow-up period (28 days after the last study dose for each cohort [approximately 60 days]). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Cohort 1: Placebo	0/3 (0%)	0/3 (0%)	2/3 (66.7%)
Cohort 1: MEDI0382 100 mcg	0/6 (0%)	0/6 (0%)	6/6 (100%)
Cohort 2: Placebo	0/3 (0%)	0/3 (0%)	3/3 (100%)
Cohort 2: MEDI0382 150 mcg	0/6 (0%)	0/6 (0%)	5/6 (83.3%)
Cohort 3: Placebo	0/3 (0%)	0/3 (0%)	3/3 (100%)
Cohort 3: MEDI0382 200 mcg	0/7 (0%)	1/7 (14.3%)	7/7 (100%)
Cohort 4: Placebo	0/26 (0%)	1/26 (3.8%)	23/26 (88.5%)
Cohort 4: MEDI0382 200 mcg	0/25 (0%)	0/25 (0%)	22/25 (88%)
Cohort 5: Placebo	0/5 (0%)	0/5 (0%)	4/5 (80%)
Cohort 5: MEDI0382 300 mcg	0/11 (0%)	0/11 (0%)	10/11 (90.9%)
Cohort 6: Placebo	0/5 (0%)	0/5 (0%)	2/5 (40%)
Cohort 6: MEDI0382 300 mcg	0/12 (0%)	0/12 (0%)	10/12 (83.3%)

Most frequent serious events

Most frequent serious events
Event	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Pneumonia mycoplasmalInfections and infestations	0/3	0/6	0/3	0/6	0/3	1/7	0/26	0/25	0/5	0/11	0/5	0/12
DiplopiaEye disorders	0/3	0/6	0/3	0/6	0/3	0/7	1/26	0/25	0/5	0/11	0/5	0/12

Most frequent other events

Showing 10 of 118

Most frequent other events
Event	Cohort 1: Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: Placebo	Cohort 2: MEDI0382 150 mcg	Cohort 3: Placebo	Cohort 3: MEDI0382 200 mcg	Cohort 4: Placebo	Cohort 4: MEDI0382 200 mcg	Cohort 5: Placebo	Cohort 5: MEDI0382 300 mcg	Cohort 6: Placebo	Cohort 6: MEDI0382 300 mcg
Decreased appetiteMetabolism and nutrition disorders	0/3	0/6	0/3	2/6	1/3	6/7	0/26	5/25	1/5	4/11	0/5	3/12
HeadacheNervous system disorders	0/3	1/6	0/3	1/6	1/3	4/7	2/26	9/25	1/5	3/11	1/5	1/12
NauseaGastrointestinal disorders	0/3	0/6	0/3	3/6	0/3	3/7	5/26	13/25	1/5	3/11	0/5	5/12
Abdominal distensionGastrointestinal disorders	0/3	3/6	0/3	0/6	0/3	1/7	0/26	6/25	0/5	2/11	0/5	0/12
DyspepsiaGastrointestinal disorders	0/3	1/6	0/3	0/6	0/3	3/7	1/26	7/25	0/5	4/11	0/5	2/12
VomitingGastrointestinal disorders	0/3	0/6	0/3	2/6	0/3	3/7	0/26	8/25	0/5	3/11	0/5	1/12
ExtrasystolesCardiac disorders	0/3	0/6	1/3	0/6	1/3	0/7	0/26	0/25	0/5	0/11	0/5	0/12
Supraventricular tachycardiaCardiac disorders	1/3	1/6	1/3	1/6	1/3	1/7	0/26	0/25	0/5	0/11	0/5	0/12
Ventricular extrasystolesCardiac disorders	0/3	1/6	1/3	1/6	0/3	0/7	1/26	1/25	0/5	0/11	0/5	0/12
Ventricular tachycardiaCardiac disorders	0/3	0/6	0/3	0/6	1/3	1/7	0/26	0/25	0/5	0/11	0/5	0/12

Baseline characteristics

As-treated Population (ATP) included all participants who received any study drug and analyzed according to the treatment they actually received.

Age, Continuous
Age, Continuous(Years)	Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg	TOTAL
Mean	57.2 ± 6.0	62.5 ± 2.9	60.2 ± 4.2	57.0 ± 4.9	56.0 ± 7.2	54.8 ± 6.8	54.6 ± 6.5	56.9 ± 6.3

Sex: Female, Male
Sex: Female, Male(Participants)	Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg	TOTAL
Female	18	1	4	2	12	4	3	44
Male	27	5	2	5	13	7	9	68

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg	TOTAL
Hispanic or Latino	0	0	0	0	0	0	0	0
Not Hispanic or Latino	45	6	6	7	25	11	12	112
Unknown or Not Reported	0	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Placebo	Cohort 1: MEDI0382 100 mcg	Cohort 2: MEDI0382 150 mcg	Cohort 3: MEDI0382 200 mcg	Cohort 4: MEDI0382 200 mcg	Cohort 5: MEDI0382 300 mcg	Cohort 6: MEDI0382 300 mcg	TOTAL
American Indian or Alaska Native	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0
Black or African American	1	0	0	0	0	0	0	1
White	44	6	6	7	25	11	12	111
More than one race	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0	0

Study locations

11 sites

Research Site
Berlin, 10117, Germany
Research Site
Erfurt, 99084, Germany
Research Site
Kiel, 24105, Germany
Research Site
Leipzig, 04103, Germany
Research Site
Lübeck, 23538, Germany
Research Site
Magdeburg, 39120, Germany
Research Site
Mainz, 55116, Germany
Research Site
Mannheim, 68167, Germany
Research Site
München, 81241, Germany
Research Site
Neu-Ulm, 89231, Germany
Research Site
Neuss, 41460, Germany

References and documents

Publications

Ambery P, Parker VE, Stumvoll M, Posch MG, Heise T, Plum-Moerschel L, Tsai LF, Robertson D, Jain M, Petrone M, Rondinone C, Hirshberg B, Jermutus L. MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet. 2018 Jun 30;391(10140):2607-2618. doi: 10.1016/S0140-6736(18)30726-8. Epub 2018 Jun 23. PubMed 29945727 ↗

Study documents

Study protocol · Sep 23, 2016
Statistical analysis plan · Mar 15, 2017

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

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Apr 5, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02548585
Lead sponsor: MedImmune LLC
Responsible party: Sponsor
First posted: Sep 14, 2015
Start date: Dec 9, 2015
Primary completion: Feb 24, 2017
Completion: Feb 24, 2017
Results posted: Apr 5, 2019
Last update: Apr 5, 2019

Study contacts

Michael Stumvoll

principal investigator · Universitätsklinikum Leipzig

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

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A Multiple-ascending-dose Study to Evaluate the Efficacy, Safety, and Pharmacokinetics (PK) of MEDI0382 in Overweight and Obese Participants With Type 2 Diabetes Mellitus

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