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CompletedPhase 1

Safety and Tolerability Study of Cotadutide in Japanese Obese Subjects With Type 2 Diabetes Melitus

A Phase 1 Randomized, Blinded, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Cotadutide in Japanese Obese Subjects With Type 2 Diabetes Mellitus

Lead sponsor

AstraZeneca

Asset

Cotadutide

Subcutaneous · GLP-1 / glucagon dual

Listed sites

3

Recruiting sites

Enrollment

16

actual

Study population

Obesity / overweight, Type 2 diabetes

Key I/E criteria

BMI 25-35HbA1c 6.5-8.5%

Primary endpoints

Treatment-emergent AEs (any)Serious AEs (any)Clinically important changes in 12-lead electrocardiogram (ECG)

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

NCT IDNCT04208620
Org study IDD5671C00003

Timeline

Milestones

Study first posted2019-12-23actual
Study start2020-01-21actual
Primary completion2020-07-08actual
Study completion2020-07-08actual
Last update posted2020-07-31actual

Assets

Investigational agents

Study populations

Who this study enrolls

Obesity / overweightType 2 diabetes

Eligibility

Who can enroll

Minimum age20 Years
Maximum age74 Years
SexAll
Healthy volunteersNot accepted

Inclusion criteria

1. Provision of signed and dated written informed consent prior to any mandatory study specific procedures, sampling, and analyses.

2. Subject must be 20 to 74 years of age at screening.

3. HbA1c range of 6.5% to 8.5% at screening and run-in visit.

4. Willing and able to self-inject investigational product for the duration of the study.

5. Individuals who are diagnosed with T2DM and have inadequate glycaemic control with diet and exercise.

6. Individuals whose current condition at enrolment are drug naïve defined as

Never received medical treatment for diabetes (insulin and/or other anti-diabetic agents [oral or injection]) OR
Received medical treatment for diabetes for less than 30 days since diagnosis.Subjects also should not have a history of insulin therapy within 2 weeks of screening (with the exception of insulin therapy during a hospitalization for other causes or use in gestational diabetes) OR
Previously received medical treatment for diabetes but have not been treated within 6 weeks of randomization.

7. BMI within the range 25 to 35 kg/m2 at screening.

8. Negative pregnancy test for female subjects.

9. Female subjects of childbearing potential who are sexually active with a male partner must be willing to use at least one highly effective method of contraception from screening and up to 4 weeks after the last dose of investigational product.

Exclusion criteria

1. Subjects with any of the following results at screening and run-in visit

2. 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.

3. Acute pancreatitis at screening or history of chronic pancreatitis or serum triglyceride levels > 11 mmol/L (1000 mg/dL) at screening.

4. Significant inflammatory bowel disease, gastroparesis or other severe disease or surgery affecting the upper GI tract (including weight-reducing surgery and procedures), which may affect gastric emptying or could affect the interpretation of safety and tolerability data.

5. Significant hepatic disease (except for NASH or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or subjects with any of the following results at screening or run-in visit.

Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN)
Alanine transaminase (ALT) ≥ 3 × ULN
Total bilirubin (TBL) ≥ 2 × ULN

6. Impaired renal function defined as estimated glomerular filtration rate (GFR) < 60 mL/minute/1.73m2 at screening or run-in visit (GFR estimated according to Modification of Diet in Renal Disease [MDRD] using MDRD Study Equation IDMS-traceable [International System of Units (SI)]).

7. Poorly controlled hypertension defined as, For age ≤ 55 years; Systolic BP > 140 mmHg Diastolic BP ≥ 90 mmHg For age > 55 years; Systolic BP > 150 mmHg Diastolic BP ≥ 90 mmHg After 10 minutes of supine rest and confirmed by repeated measurement at screening or run-in visit. Subjects who fail BP screening criteria may be considered for 24-hour or day time ABPM at the discretion of the investigator. Subjects who maintain a mean 24-hour BP < 130/80 mmHg with a preserved nocturnal dip of > 15% or day time BP < 135/85 mmHg will be considered eligible

8. Resting heart rate is ≥ 80 bpm at screening or run-in visit.

9. Any clinically important abnormalities in rhythm, conduction, or morphology of the 12-lead ECG or any abnormalities that may interfere with the interpretation of serial ECG changes, including QTc interval changes at screening, as judged by the investigator.

10. Prolonged QT intervals corrected for heart rate using Fridericia's formula (QTcF) > 450 msec, or family history of long QT-segment at screening or run-in visit.

11. PR (PQ) interval prolongation (> 220 msec), intermittent second (Wenckebach block while asleep is not exclusive), or third-degree atrioventricular (AV) block, or AV dissociation at screening or run-in visit.

12. Persistent or intermittent complete bundle branch block. A QRS duration < 120 msec is acceptable if there is no evidence of ventricular hypertrophy or preexcitation at screening or run-in visit.

13. Abnormal findings during the exercise stress test, such as chest pain, dyspnoea, presyncope, arrhytmias, signs of cardiac ischemia on ECG as judged by the investigator.

14. History of, unstable angina pectoris, myocardial infarction, transient ischemic attack, or stroke, or subjects who have undergone percutaneous coronary intervention or a coronary artery bypass graft or who are due to undergo these procedures at the time of screening.

15. Severe congestive heart failure (New York Heart Association Class III or IV).

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

17. Hemoglobinopathy, hemolytic anemia or chronic anemia (hemoglobin, < 11.5 g/dL [115 g/L]) for males, < 10.5 g/dL (105 g/L) for females) at screening or run-in visit, or any other condition known to interfere with the interpretation of HbA1c measurement.

18. 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.

19. Any positive results for serum hepatitis B surface antigen, hepatitis C antibody, and human HIV antibody.

20. 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 run-in visit. Subjects who use benzodiazepines for chronic anxiety or sleep disorders may be permitted to enter the study.

21. Symptoms of depression or any other psychiatric disorder requiring treatment with medication (eg, anti-depressants, anti-psychotics) at screening. However, subjects who use benzodiazepines for chronic anxiety or sleep disorders may be permitted to enter the study.

22. History of severe allergy/hypersensitivity, including to any component of the investigational product formulation including excipients or other biological agent, any of the proposed study treatments, or ongoing clinically important allergy/hypersensitivity.

23. Any subject who has received another investigational product as part of a clinical study or a 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.

24. Any subject who has received any of the following medications within the specified timeframe prior to the start of the study.

Herbal preparations within one week prior to the start of screening or drugs licensed for control of body weight or appetite within 30 days (or 5 half-lives of the drug) prior to the start of screening
Opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying and within 2 weeks prior to the start of dosing
Antimicrobials within the quinolone, macrolide or azole class within 2 weeks prior to the start of dosing
Any change in antihypertensive medication within 3 months prior to screening
Any change in thyroid replacement therapy within 2 months prior to screening
Aspirin at a total daily dose of greater than 150 mg
Paracetamol or paracetamol-containing preparations at a total daily dose of greater than 3000 mg
Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000 mg

25. Concurrent participation in another study of any kind and repeat randomization in this study.

26. Received Cotadutide in another clinical study prior to enrolment in this study.

Endpoints (24)

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

Safety / tolerability / PK
12
Glycemic / diabetes
7
Weight & body composition
3
Cardiometabolic biomarkers
2

Weight & body composition

3 endpoints
Secondary/protocol endpoint

Percentage change in body weight

Time frame:At baseline through end of study, 98 days in total

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

Absolute change in body weight (kg)

Time frame:At baseline through end of study, 98 days in total

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Proportion of subjects achieving > 5% body weight loss

Time frame:At baseline through end of study, 98 days in total

≥5% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

7 endpoints
Secondary/protocol endpoint

Change in average glucose levels (mg/dL)

Time frame:At baseline through end of study, 98 days in total

change from baseline, improvement

Secondary/protocol endpoint

Change in coefficient of variation

Time frame:At baseline through end of study, 98 days in total

change from baseline, improvement

Secondary/protocol endpoint

Change in percentage time spent in hyperglycemia (> 140 mg/dL)

Time frame:At baseline through end of study, 98 days in total

CGM time-above-range

percent change from baseline, improvement

Secondary/protocol endpoint

Change in percentage time spent in normoglycemia (70 -140 mg/dL)

Time frame:At baseline through end of study, 98 days in total

CGM time-in-range

change from baseline, improvement

Secondary/protocol endpoint

Change in estimated hemoglobin A1c (HbA1c)

Time frame:At baseline through end of study, 98 days in total

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change in fasting plasma glucose (mg/dL)

Time frame:At baseline through end of study, 98 days in total

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Change in HbA1c

Time frame:At baseline through end of study, 98 days in total

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Cardiometabolic biomarkers

2 endpoints
Primary/protocol endpoint

Vital signs as measured by pulse rate (bpm)

Time frame:Baseline until the follow-up period, 28 days post-last dose

Heart rate, change

change from baseline, descriptive

Primary/protocol endpoint

ABPM (Ambulatory blood pressure monitoring) to measure pulse rate (bpm) and blood pressure (mmHg)

Time frame:Baseline until the follow-up period, 28 days post-last dose

descriptive

Safety / tolerability / PK

12 endpoints
Primary/protocol endpoint

Incidence of treatment-emergent adverse events (TEAEs)

Time frame:Baseline until the follow-up period, 28 days post-last dose

Treatment-emergent AEs (any)

event count, event

Primary/protocol endpoint

Incidence of treatment-emergent serious adverse events (TESAEs)

Time frame:Baseline until the follow-up period, 28 days post-last dose

Serious AEs (any)

event count, event

Primary/protocol endpoint

Clinically important changes in 12-lead electrocardiogram (ECG)

Time frame:Baseline until the follow-up period, 28 days post-last dose

descriptive

Primary/protocol endpoint

Vital signs as measured by blood pressure (mmHg)

Time frame:Baseline until the follow-up period, 28 days post-last dose

descriptive

Primary/protocol endpoint

Physical examination (abnormality to be reported as part of adverse events)

Time frame:Baseline until the follow-up period, 28 days post-last dose

descriptive

Primary/protocol endpoint

Clinical laboratory evaluations

Time frame:Baseline until the follow-up period, 28 days post-last dose

descriptive

Secondary/protocol endpoint

Area under the concentration-time curve (AUC) during the dosing interval (AUCtau)

Time frame:Day1 of Up-titration treatment period to Day 21 of Treatment extension period, total of up to 10 weeks

AUC₀–∞

concentration, descriptive

Secondary/protocol endpoint

Maximum observed concentration (Cmax)

Time frame:Day1 of Up-titration treatment period to Day 21 of Treatment extension period, total of up to 10 weeks

Cmax

concentration, descriptive

Secondary/protocol endpoint

Time to Cmax (tmax)

Time frame:Day1 of Up-titration treatment period to Day 21 of Treatment extension period, total of up to 10 weeks

Tmax

descriptive

Secondary/protocol endpoint

Trough plasma concentration (Ctrough)

Time frame:Day1 of Up-titration treatment period to Day 21 of Treatment extension period, total of up to 10 weeks

Plasma concentration (steady state)

concentration, descriptive

Secondary/protocol endpoint

Anti-drug antibodies (ADAs) to Cotadutide

Time frame:At baseline through end of study, 98 days in total

Immunogenicity (ADA)

descriptive

Secondary/protocol endpoint

Change in percentage time spent in clinically significant hypoglycemia (< 54 mg/dL)

Time frame:At baseline through end of study, 98 days in total

CGM time-below-range

change from baseline, event

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.

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableno registry results posted yet

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.