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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
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 25-35•HbA1c 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
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
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
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.
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.
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
Weight & body composition
3 endpointsPercentage change in body weight
Time frame:At baseline through end of study, 98 days in total
Body weight, % change
percent change from baseline, improvement
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
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 endpointsChange in average glucose levels (mg/dL)
Time frame:At baseline through end of study, 98 days in total
change from baseline, improvement
Change in coefficient of variation
Time frame:At baseline through end of study, 98 days in total
change from baseline, improvement
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
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
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
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
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 endpointsVital 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
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 endpointsIncidence 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
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
Clinically important changes in 12-lead electrocardiogram (ECG)
Time frame:Baseline until the follow-up period, 28 days post-last dose
descriptive
Vital signs as measured by blood pressure (mmHg)
Time frame:Baseline until the follow-up period, 28 days post-last dose
descriptive
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
Clinical laboratory evaluations
Time frame:Baseline until the follow-up period, 28 days post-last dose
descriptive
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
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
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
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
Anti-drug antibodies (ADAs) to Cotadutide
Time frame:At baseline through end of study, 98 days in total
Immunogenicity (ADA)
descriptive
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.
Registry references + supporting bibliography
- Diabetes, obesity & metabolism2023 Aug (month)PMID37337366doi:10.1111/dom.15107via 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.