← Trials/Trial dossier/NCT03244800
A Study to Investigate Different Doses of 0382 in Overweight and Obese Subjects With Type 2 Diabetes Mellitus.
A Phase 2, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Different Doses of MEDI0382 in Overweight and Obese Subjects With Type 2 Diabetes Mellitus
Lead sponsor
Asset
Cotadutide
Subcutaneous · GLP-1 / glucagon dual
Listed sites
5
Recruiting sites
—
Enrollment
65
actual
Study population
Obesity / overweight, Type 2 diabetes
Key I/E criteria
•BMI 27-40•HbA1c 6.5-8.5%
Primary endpoints
•Postprandial glucose•Body weight, % change
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion criteria
1. Male and female subjects aged ≥ 18 years at screening
2. Provision of signed and dated written informed consent
3. BMI between 27 and 40 kg/m2
4. HbA1c range of 6.5% to 8.5%
5. Diagnosed with T2DM with glucose control managed with metformin monotherapy where no significant dose change (increase or decrease ≥ 500 mg/day) has occurred in the 3 months prior to screening
6. Subjects prescribed oral dual therapy with a dipeptidyl peptidase-4 inhibitor, sulphonylurea, glitinide, or a sodium-glucose co-transporter 2 inhibitor in addition to metformin at screening may be eligible to enter the study following a 4-week washout period
7. Female subjects of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating
8. Females of childbearing potential who are sexually active with a nonsterilised male partner must use at least one highly effective method of contraception from screening and must agree to continue using such precautions through to the end of the study. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
Exclusion criteria
1. History of, or any existing condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures
2. Concurrent participation in another study of any kind and repeat randomisation in this study is prohibited
3. Severe allergy/hypersensitivity to any of the proposed study treatments
4. 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 subject has been treated with daily SC insulin within 90 days prior to screening
5. Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper GI tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
6. Significant hepatic disease (except for non-alcoholic steatohepatitis or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening:
7. Impaired renal function defined as estimated glomerular filtration rate (GFR) < 60 mL/minute/1.73 m2 at screening (GFR estimated according to Modification of Diet in Renal Disease [MDRD] using the isotope dilution mass spectrometry [IDMS] traceable MDRD Study Equation [SI units])
8. Poorly controlled hypertension defined as:
9. Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke within 3 months prior to screening, or subjects 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
10. Severe congestive heart failure (New York Heart Association Class III or IV)
11. Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
12. Haemoglobinopathy, haemolytic anemia, or chronic anaemia (haemoglobin concentration < 11.5 g/dL [115 g/L] for males, < 10.5 g/dL [105 g/L] for females) at screening or any other condition known to interfere with interpretation of HbA1c measurement
13. 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
14. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody
15. History of substance dependence, alcohol abuse, or excessive alcohol intake (defined as an average weekly intake of > 21 alcoholic drinks for men or > 10 alcoholic drinks for women) within 3 years prior to screening, and/or a positive screen for drugs of abuse or alcohol at screening or on admission to the study unit. Subjects who use tricyclic antidepressants or benzodiazepines for an established clinical indication may be permitted to enter the study based upon the judgement of the investigator.
16. Involvement of any AstraZeneca, MedImmune, contract research organization, or study site employee or their close relatives
17. History of acute or chronic pancreatitis or other diseases of the pancreas
Endpoints (25)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Weight & body composition
3 endpointsCohort 1: Percent Change From Baseline in Body Weight to Day 50
Time frame:Day 1 through Day 50
Body weight, % change
percent change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), Percent change | 95% CI |
|---|---|---|
| Placebo Cohort 1 | -0.21 | -1.88 – 1.46 |
| MEDI0382 Cohort 1 | -3.59 | -4.77 – -2.41 |
Cohort 1: Change From Baseline in Body Weight to Day 50
Time frame:Day 1 through Day 50
Body weight, absolute change (kg)
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), Kilogram | 95% CI |
|---|---|---|
| Placebo Cohort 1 | -0.08 | -1.45 – 1.28 |
| MEDI0382 Cohort 1 | -3.41 | -4.37 – -2.44 |
Cohort 1: Percentage of Participants Achieving Greater Than or Equal to 5% Body Weight Loss From Baseline to Day 50
Time frame:Day 1 through Day 50
≥5% weight-loss responders
threshold achievement, improvement
Posted result
| Group | Value (number), Percentage of Participants | 95% CI |
|---|---|---|
| Placebo Cohort 1 | 7.7 | — |
| MEDI0382 Cohort 1 | 42.3 | — |
Glycemic / diabetes
4 endpointsCohort 1: Percent Change From Baseline in Plasma Glucose Area Under the Concentration-time Curve From Time 0 to 4 Hours (AUC0-4h) by Mixed-meal Tolerance Test (MMTT) to Day 49
Time frame:Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal
Postprandial glucose
percent change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), Percent change | 95% CI |
|---|---|---|
| Placebo Cohort 1 | 6.32 | -0.74 – 13.38 |
| MEDI0382 Cohort 1 | -21.52 | -26.51 – -16.54 |
Cohort 1: Change From Baseline in Glycated Haemoglobin (HbA1c) to Day 49
Time frame:Baseline (Day -1) through Day 49
HbA1c, change
change from baseline, improvement
LOINC 4548-4
Posted result
| Group | Value (least_squares_mean), Percentage change | 95% CI |
|---|---|---|
| Placebo Cohort 1 | -0.07 | -0.27 – 0.14 |
| MEDI0382 Cohort 1 | -0.67 | -0.82 – -0.53 |
Cohort 1: Change From Baseline in Fasting Plasma Glucose to Day 49
Time frame:Baseline (Day -1) through Day 49
Fasting glucose, change
change from baseline, improvement
LOINC 1558-6
Posted result
| Group | Value (least_squares_mean), mg/dL | 95% CI |
|---|---|---|
| Placebo Cohort 1 | -2.31 | -12.74 – 8.13 |
| MEDI0382 Cohort 1 | -35.37 | -42.75 – -27.99 |
Cohort 1 and Cohort 2: Percent Change From Baseline in MMTT Plasma Glucose AUC 0-4h to Day 7
Time frame:Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised liquid meal
Postprandial glucose
percent change from baseline, improvement
Posted result
| Group | Value (mean), Percent change | 95% CI |
|---|---|---|
| Placebo Cohort 1 | -2.02 | — |
| MEDI0382 Cohort 1 | -27.17 | — |
| Placebo Cohort 2 | 1.77 | — |
| MEDI0382 Cohort 2 | -31.80 | — |
Safety / tolerability / PK
18 endpointsCohort 1 and Cohort 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame:From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)
Treatment-emergent AEs (any)
event count, event
componentsTreatment-emergent AEs (any), Serious AEs (any)
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| Placebo Cohort 1TEAEs | 6 | — |
| TESAEs | 0 | — |
| MEDI0382 Cohort 1TEAEs | 22 | — |
| TESAEs | 0 | — |
| Placebo Cohort 2TEAEs | 3 | — |
| TESAEs | 0 | — |
| MEDI0382 Cohort 2TEAEs | 15 | — |
| TESAEs | 0 | — |
Cohort 1 and Cohort 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs
Time frame:From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)
Treatment-emergent AEs (any)
event count, event
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| Placebo Cohort 1 | 0 | — |
| MEDI0382 Cohort 1 | 0 | — |
| Placebo Cohort 2 | 0 | — |
| MEDI0382 Cohort 2 | 0 | — |
Cohort 1 and Cohort 2: Number of Participants With Abnormal Electrocardiogram Reported as TEAEs
Time frame:From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)
Treatment-emergent AEs (any)
event count, event
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| Placebo Cohort 1 | 0 | — |
| MEDI0382 Cohort 1 | 0 | — |
| Placebo Cohort 2 | 0 | — |
| MEDI0382 Cohort 2 | 1 | — |
Cohort 1 and Cohort 2: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Time frame:From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)
Treatment-emergent AEs (any)
event count, event
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| Placebo Cohort 1Thrombocytopenia | 0 | — |
| Hypoglycaemia | 0 | — |
| MEDI0382 Cohort 1Thrombocytopenia | 0 | — |
| Hypoglycaemia | 1 | — |
| Placebo Cohort 2Thrombocytopenia | 0 | — |
| Hypoglycaemia | 0 | — |
| MEDI0382 Cohort 2Thrombocytopenia | 1 | — |
| Hypoglycaemia | 1 | — |
Cohort 1 and Cohort 2: Number of Participants With Injection Site Erythema
Time frame:From Day 1 through 7 to 14 days after the last dose of study drug (approximately 64 days)
event count, event
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| Placebo Cohort 1 | 0 | — |
| MEDI0382 Cohort 1 | 0 | — |
| Placebo Cohort 2 | 0 | — |
| MEDI0382 Cohort 2 | 5 | — |
Cohort 1: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382
Time frame:Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49
AUC₀–∞
concentration, descriptive
Posted result
| Group | Value (geometric_mean), ng*hr/mL | 95% CI |
|---|---|---|
| MEDI0382 Cohort 1Day 22 | 226.31 | 103.95 – 488.98 |
| Day 49 | 248.83 | 86.57 – 558.57 |
Cohort 2: Area Under the Concentration-time Curve During the Dosing Interval (AUCt) of MEDI0382
Time frame:Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14
AUC₀–∞
concentration, descriptive
Posted result
| Group | Value (geometric_mean), ng*hr/mL | 95% CI |
|---|---|---|
| MEDI0382 Cohort 2Day 1 | 38.67 | 34.05 – 47.25 |
| Day 7 | 37.51 | 8.99 – 69.82 |
| Day 14 | 46.75 | 26.38 – 65.61 |
Cohort 1: Maximum Observed Concentration (Cmax) of MEDI0382
Time frame:Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49
Cmax
concentration, descriptive
Posted result
| Group | Value (geometric_mean), ng/mL | 95% CI |
|---|---|---|
| MEDI0382 Cohort 1Day 22 | 13.24 | 4.89 – 30.3 |
| Day 49 | 14.8 | 5.76 – 33.3 |
Cohort 2: Maximum Observed Concentration (Cmax) of MEDI0382
Time frame:Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14
Cmax
concentration, descriptive
Posted result
| Group | Value (geometric_mean), ng/mL | 95% CI |
|---|---|---|
| MEDI0382 Cohort 2Day 1 | 2.00 | 1.09 – 3.25 |
| Day 7 | 2.53 | 0.85 – 4.14 |
| Day 14 | 2.65 | 1.50 – 3.77 |
Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382
Time frame:Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49
Tmax
descriptive
Posted result
| Group | Value (median), Hours | 95% CI |
|---|---|---|
| MEDI0382 Cohort 1Day 22 | 6 | 4 – 12 |
| Day 49 | 4 | 2 – 8 |
Cohort 2: Time to Reach Maximum Observed Concentration (Tmax) of MEDI0382
Time frame:Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14
Tmax
descriptive
Posted result
| Group | Value (median), Hours | 95% CI |
|---|---|---|
| MEDI0382 Cohort 2Day 1 | 8 | 4 – 12 |
| Day 7 | 6 | 0 – 8 |
| Day 14 | 6 | 4 – 12 |
Cohort 1: Terminal Half Life (t1/2) of MEDI0382
Time frame:Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49
Half-life
descriptive
Posted result
| Group | Value (geometric_mean), Hours | 95% CI |
|---|---|---|
| MEDI0382 Cohort 1Day 22 | 9.67 | 9.67 – 9.67 |
| Day 49 | 8.4 | 7.7 – 9.4 |
Cohort 2: Terminal Half Life (t1/2) of MEDI0382
Time frame:Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14
Half-life
descriptive
Posted result
| Group | Value (geometric_mean), Hours | 95% CI |
|---|---|---|
| MEDI0382 Cohort 2Day 1 | 9.7 | 8.9 – 10.2 |
| Day 7 | 8.8 | 8.6 – 9.0 |
| Day 14 | 9.4 | 8.7 – 10.5 |
Cohort 1: Accumulation Ratio (Racc) of MEDI0382
Time frame:Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49
AUC₀–∞
ratio, descriptive
Posted result
| Group | Value (geometric_mean), Ratio | 95% CI |
|---|---|---|
| MEDI0382 Cohort 1 | 1.46 | 1.13 – 2.98 |
Cohort 2: Accumulation Ratio of MEDI0382
Time frame:Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14
ratio, descriptive
Posted result
| Group | Value (geometric_mean), Ratio | 95% CI |
|---|---|---|
| MEDI0382 Cohort 2Day 7 | 1.36 | 1.2 – 1.6 |
| Day 14 | 1.46 | 1.2 – 1.9 |
Cohort 1: Trough Plasma Concentration (Ctrough) of MEDI0382
Time frame:Cohort 1: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 22 and 49
Plasma concentration (steady state)
concentration, descriptive
Posted result
| Group | Value (geometric_mean), ng/mL | 95% CI |
|---|---|---|
| MEDI0382 Cohort 1Day 22 | 3.566 | 0.50 – 9.27 |
| Day 49 | 5.762 | 1.53 – 11.80 |
Cohort 2: Trough Plasma Concentration (Ctrough) of MEDI0382
Time frame:Cohort 2: Predose and 1, 2, 4, 6, 8, and 12 hours postdose on Days 1, 7, and 14
Plasma concentration (steady state)
concentration, descriptive
Posted result
| Group | Value (geometric_mean), ng/mL | 95% CI |
|---|---|---|
| MEDI0382 Cohort 2Day 7 | 1.147 | 0.79 – 2.36 |
| Day 14 | 1.147 | 0.69 – 1.92 |
Cohort 1 and Cohort 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0382
Time frame:Baseline (Day 1), Day 29, Day 50, and Follow-up Visit 2 (28 days after the last dose [approximately 64 days])
Immunogenicity (ADA)
threshold achievement, event
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| Placebo Cohort 1Baseline (ADA positive) | 0 | — |
| Day 29 (ADA positive) | 0 | — |
| Day 50 (ADA positive) | 0 | — |
| Follow-up Visit 2 (ADA positive) | 1 | — |
| MEDI0382 Cohort 1Baseline (ADA positive) | 0 | — |
| Day 29 (ADA positive) | 4 | — |
| Day 50 (ADA positive) | 7 | — |
| Follow-up Visit 2 (ADA positive) | 6 | — |
| Placebo Cohort 2Baseline (ADA positive) | 0 | — |
| Day 29 (ADA positive) | 0 | — |
| Day 50 (ADA positive) | 0 | — |
| Follow-up Visit 2 (ADA positive) | 0 | — |
| MEDI0382 Cohort 2Baseline (ADA positive) | 0 | — |
| Day 29 (ADA positive) | 1 | — |
| Day 50 (ADA positive) | 2 | — |
| Follow-up Visit 2 (ADA positive) | 6 | — |
Publications (1)
Bibliography
Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.
Registry references + supporting bibliography
- The Journal of clinical endocrinology and metabolism2020 Mar 1PMID31608926doi:10.1210/clinem/dgz047via clinicaltrials gov reference derived + pubmed nct search
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.