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A Study to Look at the Effect MEDI0382 Has on Blood Sugar in People With Type 2 Diabetes and Kidney Problems and Also to Check That MEDI0382 is Well Tolerated
A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of MEDI0382 in Subjects With Type 2 Diabetes Mellitus and Renal Impairment
Lead sponsor
Asset
Cotadutide
Subcutaneous · GLP-1 / glucagon dual
Listed sites
7
Recruiting sites
—
Enrollment
41
actual
Study population
Renal impairment, Type 2 diabetes
Key I/E criteria
•BMI 25-45•HbA1c 6.5-10.5%•eGFR 30-60
Primary endpoint
•Postprandial glucose
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. Age ≥ 18 and < 85 years at screening.
2. Signed and dated written informed consent (with the exception of consent for genetic and nongenetic research) prior to performing any protocol-related procedures, including screening evaluations.
3. Diagnosed with type 2 diabetes mellitus (T2DM) with glucose control managed with any insulin and/or oral therapy combination where no significant dose changes of oral therapy of more than 50% have occurred in the 3 months prior to screening
4. Body mass index (BMI) between 25 and 45 kg/m^2 (inclusive) at screening
5. Haemoglobin A1c (HbA1c) range of 6.5 % to 10.5% (inclusive) at screening
6. Renal impairment with estimated glomerular filtration rate (eGFR) ≥ 30 and < 60 mL/min/1.73 m^2 at screening. Approximately 16 participants (40%) are required to have a screening eGFR ≥30 and < 45 mL/min/1.73 m^2 and at least 16 participants (40%) are required to have screening eGFR ≥45 and < 60 mL/min/1.73 m^2.
7. Females of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating. Women of childbearing potential who are sexually active with a non-sterilized male partner must be using at least one highly effective method of contraception from screening and up to 4 weeks after the last dose study drug.
Exclusion criteria
1. History or presence of significant medical or psychological conditions, including substance dependence/abuse, or significant abnormalities in laboratory parameters or vital signs including electrocardiogram (ECG), which in the opinion of the investigator, would compromise the participant's safety or successful participation in the study. As an example, severe anaemia (haemoglobin < 7.0 g/dL) could be exclusionary due to blood sampling required by the protocol, at the discretion of investigator.
2. Concurrent participation in another interventional study of any kind and repeat randomisation in this study is prohibited.
3. 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 (if known; whichever is longer) at the time of Visit 2.
4. Any participant who has received any of the following medications within the specified timeframe prior to the start of the study (Visit 2)
5. Severe allergy/hypersensitivity to any of the proposed study treatments 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
7. Participants who have undergone a renal transplant
8. Participants with suspicion of acute or subacute renal function deterioration (eg, participants with large fluctuations of creatinine values documented within the 6 months prior to screening)
9. Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper gastrointestinal (GI) tract including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
10. History of acute or chronic pancreatitis
11. Significant hepatic disease (except for non-alcoholic steatohepatitis or nonalcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results:
12. Poorly controlled hypertension defined as:
13. 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
14. Severe congestive heart failure (New York Heart Association Class III or IV)
15. Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
16. History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell skin cancer, squamous cell skin cancer, or in situ cervical cancer
17. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody, and human immunodeficiency virus (HIV) antibody
18. Nephrotic range proteinuria defined as spot urine albumin creatinine ratio (ACR) > 250 mg/mmol at screening
19. 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 Day -5. Participants 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
Endpoints (19)
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
2 endpointsPercent Change Frome Baseline in Body Weight to Day 33
Time frame:Day 1 (Baseline) and Day 33
Body weight, % change
percent change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), Percent change in body weight | 95% CI |
|---|---|---|
| Placebo | -0.21 | -1.05 – 0.62 |
| MEDI0382 | -3.69 | -4.55 – -2.83 |
Change From Baseline in Absolute Body Weight to Day 33
Time frame:Day 1 (Baseline) and Day 33
Body weight, absolute change (kg)
change from baseline, improvement
Posted result
| Group | Value (mean), Kg | 95% CI |
|---|---|---|
| Placebo | -0.15 | — |
| MEDI0382 | -3.39 | — |
Glycemic / diabetes
4 endpointsPercent Change From Baseline in Plasma Glucose Area Under the Concentration Time-curve From Time 0 to 4 Hours (AUC0-4 Hrs) as Measured by Mixed-meal Tolerance Test (MMTT) to Day 32
Time frame:Zero minutes before and 15, 30, 45, 60, 90, 120, 180, and 240 minutes after consumption of the standardised meal on Day -5 (Baseline) and Day 32
Postprandial glucose
percent change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), Percent change in plasma glucose | 95% CI |
|---|---|---|
| Placebo | 3.678 | -3.793 – 11.149 |
| MEDI0382 | -26.706 | -34.584 – -18.828 |
Change From Baseline in Haemoglobin A1c (HbA1c) to Day 32
Time frame:Day 1 (Baseline) and Day 32
HbA1c, change
change from baseline, improvement
LOINC 4548-4
Posted result
| Group | Value (least_squares_mean), Percent | 95% CI |
|---|---|---|
| Placebo | 0.01 | -0.15 – 0.17 |
| MEDI0382 | -0.65 | -0.82 – -0.49 |
Change From Baseline in Fasting Glucose to Day 32
Time frame:Day 1 (Baseline) and Day 32
Fasting glucose, change
change from baseline, improvement
LOINC 1558-6
Posted result
| Group | Value (least_squares_mean), mg/dL | 95% CI |
|---|---|---|
| Placebo | 0.60 | -12.89 – 14.08 |
| MEDI0382 | -19.55 | -33.39 – -5.71 |
Change From Baseline in Percentage of Time Spent Within a Target Glucose Range Over a 7-day Period to the Final Week of Treatment
Time frame:Baseline (Days -8 to -2), Days 5 to 11, Days 12 to 18, Days 19 to 25, and Days 26 to 32 (final week of treatment)
CGM time-in-range
change from baseline, improvement
Posted result
| Group | Value (least_squares_mean), Percentage of time | 95% CI |
|---|---|---|
| PlaceboDays 5 - 11 | -10.49 | -20.77 – -0.20 |
| Days 12 - 18 | -5.34 | -12.77 – 2.10 |
| Days 19 - 25 | -16.05 | -25.02 – -7.08 |
| Days 26 - 32 | -21.23 | -33.13 – -9.32 |
| MEDI0382Days 5 - 11 | 12.25 | 2.52 – 21.98 |
| Days 12 - 18 | 15.62 | 8.39 – 22.86 |
| Days 19 - 25 | 19.18 | 10.21 – 28.15 |
| Days 26 - 32 | 14.79 | 2.54 – 27.04 |
Cardiometabolic biomarkers
3 endpointsChange From Baseline in Postural Blood Pressure
Time frame:Baseline (Day 1) through Day 32
change from baseline, improvement
Posted result
| Group | Value (mean), mmHg | 95% CI |
|---|---|---|
| PlaceboSystolic Blood Pressure | 0.1 | — |
| Diastolic Blood Pressure | 1.8 | — |
| MEDI0382Systolic Blood Pressure | 8.9 | — |
| Diastolic Blood Pressure | 0.8 | — |
Change From Baseline in Mean 24-hrs Pulse Rate to the End of Each Dosing Level
Time frame:Day -5 (Baseline) and on Days 5, 12, 19, and 32
Heart rate, change
change from baseline, improvement
Posted result
| Group | Value (mean), Beats/min | 95% CI |
|---|---|---|
| PlaceboDay 5 | -0.73 | — |
| Day 12 | 1.04 | — |
| Day 19 | 1.32 | — |
| Day 32 | -0.92 | — |
| MEDI0382Day 5 | 6.40 | — |
| Day 12 | 9.01 | — |
| Day 19 | 12.72 | — |
| Day 32 | 11.85 | — |
Change From Baseline in Mean 24-hrs Systolic and Diastolic Blood Pressure to the End of Each Dosing Level
Time frame:Day -5 (Baseline) and on Days 5, 12, 19, and 32
change from baseline, improvement
Posted result
| Group | Value (mean), mmHg | 95% CI |
|---|---|---|
| PlaceboDay 5: Systolic Blood Pressure | -3.11 | — |
| Day 12: Systolic Blood Pressure | -2.67 | — |
| Day 19: Systolic Blood Pressure | -3.56 | — |
| Day 32: Systolic Blood Pressure | 2.21 | — |
| Day 5: Diastolic Blood Pressure | -0.07 | — |
| Day 12: Diastolic Blood Pressure | -0.55 | — |
| Day 19: Diastolic Blood Pressure | -0.44 | — |
| Day 32: Diastolic Blood Pressure | 1.84 | — |
| MEDI0382Day 5: Systolic Blood Pressure | -1.69 | — |
| Day 12: Systolic Blood Pressure | -4.34 | — |
| Day 19: Systolic Blood Pressure | -4.72 | — |
| Day 32: Systolic Blood Pressure | -1.15 | — |
| Day 5: Diastolic Blood Pressure | 1.15 | — |
| Day 12: Diastolic Blood Pressure | 1.28 | — |
| Day 19: Diastolic Blood Pressure | 0.76 | — |
| Day 32: Diastolic Blood Pressure | 2.54 | — |
Safety / tolerability / PK
10 endpointsNumber of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time frame:Day 1 through Day 60
descriptive
componentsTreatment-emergent AEs (any), Serious AEs (any)
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| PlaceboTEAEs | 13 | — |
| TESAEs | 2 | — |
| MEDI0382TEAEs | 20 | — |
| TESAEs | 2 | — |
Number of Participants With Abnormal Vital Signs Reported as TEAEs
Time frame:Day 1 through Day 60
Treatment-emergent AEs (any)
event count, event
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| Placebo | 0 | — |
| MEDI0382 | 0 | — |
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
Time frame:Day 1 through Day 60
Treatment-emergent AEs (any)
event count, event
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| PlaceboBradyarrhythmia | 1 | — |
| Bundle branch block left | 1 | — |
| Bundle branch block right | 0 | — |
| MEDI0382Bradyarrhythmia | 0 | — |
| Bundle branch block left | 0 | — |
| Bundle branch block right | 1 | — |
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
Time frame:Day 1 through Day 60
Treatment-emergent AEs (any)
event count, event
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| PlaceboHypoglycaemia | 1 | — |
| Alanine aminotransferase increased | 1 | — |
| Aspartate aminotransferase increased | 1 | — |
| Glomerular filtration rate decreased | 0 | — |
| MEDI0382Hypoglycaemia | 3 | — |
| Alanine aminotransferase increased | 0 | — |
| Aspartate aminotransferase increased | 0 | — |
| Glomerular filtration rate decreased | 1 | — |
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESIs)
Time frame:Day 1 through Day 60
Treatment-emergent AEs (any)
event count, event
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| Placebo | 0 | — |
| MEDI0382 | 0 | — |
Area Under the Plasma Concentration Time Curve Over a Dosing Duration (AUCτ) of MEDI0382 at 300 μg
Time frame:Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32
AUC₀–∞
concentration, descriptive
Posted result
| Group | Value (geometric_mean), ng.hr/mL | 95% CI |
|---|---|---|
| MEDI0382 | 285.93 | 124.08 – 669.17 |
Maximum Observed Serum Concentration (Cmax) of MEDI0382 at 300 μg
Time frame:Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32
Cmax
concentration, descriptive
Posted result
| Group | Value (geometric_mean), ng/mL | 95% CI |
|---|---|---|
| MEDI0382 | 16.93 | 5.17 – 35.4 |
Time to Observed Maximum Serum Concentration (Tmax) of MEDI0382 at 300 μg
Time frame:Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose on Day 32
Tmax
concentration, descriptive
Posted result
| Group | Value (median), Hours | 95% CI |
|---|---|---|
| MEDI0382 | 5.6 | 4 – 24 |
Trough Plasma Concentration (Ctrough) of MEDI0382
Time frame:Days 1, 5, 12, and 19: Predose; and Day 32: Predose and at 0.5, 1, 2, 4, 6, 8, and 24 hrs postdose (Day 33)
Plasma concentration (steady state)
concentration, descriptive
Posted result
| Group | Value (geometric_mean), ng/mL | 95% CI |
|---|---|---|
| MEDI0382Day 5 | 1.44 | 0.48 – 2.58 |
| Day 12 | 2.03 | 0.63 – 3.75 |
| Day 19 | 3.68 | 0.59 – 8.86 |
| Day 32 | 5.86 | 1.3 – 19.4 |
| Day 33 | 5.96 | 2.43 – 19.2 |
Number of Participants With Positive Anti-drug Antibodies (ADA) Titre to MEDI0382
Time frame:Pre-dose on Days 1, 12, and 32 and on Day 60
Immunogenicity (ADA)
descriptive
Posted result
| Group | Value (count_of_participants), Participants | 95% CI |
|---|---|---|
| PlaceboPositive at baseline | 0 | — |
| Positive post-baseline | 0 | — |
| Positive at baseline and post-baseline | 0 | — |
| Not detected at baseline; positive post-baseline | 0 | — |
| Positive at baseline; not detected post-baseline | 0 | — |
| MEDI0382Positive at baseline | 0 | — |
| Positive post-baseline | 2 | — |
| Positive at baseline and post-baseline | 0 | — |
| Not detected at baseline; positive post-baseline | 2 | — |
| Positive at baseline; not detected post-baseline | 0 | — |
Publications (2)
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 Cochrane database of systematic reviews2025 Feb 18PMID39963952doi:10.1002/14651858.CD015849.pub2via clinicaltrials gov reference derived + pubmed nct search
- Diabetes, obesity & metabolism2022 Jul (month)PMID35403793doi:10.1111/dom.14712via 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.