- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04515849
A Study of Cotadutide in Participants Who Have Chronic Kidney Disease With Type 2 Diabetes Mellitus
A Phase 2b, Multicentre, Randomised, Double-blind, Placebo-controlled, and Open-label Comparator Study of Cotadutide in Participants Who Have Chronic Kidney Disease With Type 2 Diabetes Mellitus
Study Overview
Status
Conditions
Detailed Description
A Phase 2b randomised, double-blind, placebo-controlled and open-label active comparator study to evaluate the effect of Cotadutide at 100, 300 or 600 micrograms in participants who have Chronic Kidney Disease with Type 2 Diabetes Mellitus.
The study plans to randomise approximately 225 subjects. Subjects will be randomised to receive double-blind Cotadutide or placebo at 100, 300 or 600 micrograms once daily for 26 weeks, or open-label semaglutide at 1.0 miligrams once a week for 26 weeks. Japanese participants will not be randomised to the semaglutide arm.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Box Hill, Australia, 3128
- Research Site
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Elizabeth Vale, Australia, 5112
- Research Site
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Fitzroy, Australia, 3065
- Research Site
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Heidelberg, Australia, 3084
- Research Site
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Melbourne, Australia, 3004
- Research Site
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Merewether, Australia, 2291
- Research Site
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Oaklands Park, Australia, 5046
- Research Site
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Wollongong, Australia, 2500
- Research Site
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Woolloongabba, Australia, 4102
- Research Site
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British Columbia
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Vancouver, British Columbia, Canada, V5Y 3W2
- Research Site
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Ontario
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Barrie, Ontario, Canada, L4N 7L3
- Research Site
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Brampton, Ontario, Canada, L6S 0C6
- Research Site
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Concord, Ontario, Canada, L4K 4M2
- Research Site
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Etobicoke, Ontario, Canada, M9R 4E1
- Research Site
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Oakville, Ontario, Canada, L6M 1M1
- Research Site
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Ottawa, Ontario, Canada, K2J 0V2
- Research Site
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Toronto, Ontario, Canada, M4G 3E8
- Research Site
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Waterloo, Ontario, Canada, N2J 3Z4
- Research Site
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Quebec
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Laval, Quebec, Canada, H7T 2P5
- Research Site
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Montreal, Quebec, Canada, H4A 2C6
- Research Site
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Berlin, Germany, 10409
- Research Site
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Berlin, Germany, 10437
- Research Site
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Dortmund, Germany, 44137
- Research Site
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Dusseldorf, Germany, 40210
- Research Site
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Essen, Germany, 45359
- Research Site
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Ludwigshafen, Germany, 67059
- Research Site
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Magdeburg, Germany, 39120
- Research Site
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Mainz, Germany, 55116
- Research Site
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München, Germany, 81241
- Research Site
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Münster, Germany, 48153
- Research Site
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Münster, Germany, 48145
- Research Site
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Arakawa-ku, Japan, 116-0012
- Research Site
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Chitose-shi, Japan, 066-0032
- Research Site
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Fujisawa-shi, Japan, 251-0041
- Research Site
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Kamakura-shi, Japan, 247-8533
- Research Site
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Obihiro-shi, Japan, 080-0848
- Research Site
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Sapporo-shi, Japan, 060-0062
- Research Site
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Shinjyuku-ku, Japan, 160-0022
- Research Site
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Auckland, New Zealand, 2025
- Research Site
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Auckland, New Zealand, ?0620
- Research Site
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Christchurch, New Zealand, 8011
- Research Site
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Grafton, New Zealand, 1010
- Research Site
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Havelock North, New Zealand, 4130
- Research Site
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Tauranga, New Zealand, 3110
- Research Site
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Wellington, New Zealand, 6021
- Research Site
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Białystok, Poland, 15-435
- Research Site
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Krakow, Poland, 30-033
- Research Site
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Krakow, Poland, 31-261
- Research Site
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Lublin, Poland, 20064
- Research Site
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New York, Poland, 40-081
- Research Site
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Poznań, Poland, 61-655
- Research Site
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Warszawa, Poland, 02-507
- Research Site
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Barcelona, Spain, 08036
- Research Site
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Cordoba, Spain, 14004
- Research Site
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L'Hospitalet de Llobregat, Spain, 08907
- Research Site
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La Coruna, Spain, 15006
- Research Site
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Lérida, Spain, 25198
- Research Site
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Majadahonda, Spain, 28222
- Research Site
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Malaga, Spain, 29010
- Research Site
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Palma de Mallorca, Spain, 07010
- Research Site
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Pozuelo de Alarcón, Spain, 28223
- Research Site
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Sevilla, Spain, 41009
- Research Site
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Sevilla, Spain, 41003
- Research Site
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Valencia, Spain, 46009
- Research Site
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London, United Kingdom, SE5 9RS
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Estimated glomerular filtration rate ≥ 20 to < 90 mL/min/1.73 m2 determined at the screening visit or a documented occurrence in medical history at least 3 months prior to randomisation.
- Receiving background standard of care treatment for renal disease and/or T2DM and being treated according to locally recognised guidelines, as appropriate.
- Receiving optimised and stable treatment with an angiotensin-converting-enzyme (ACE) inhibitor or an angiotensin II receptor antagonist for ≥ 3 months at screening at the maximum tolerated dose (MTD) unless contraindicated, not tolerated, or in the opinion of the investigator, not practically available or suitable.
- Micro- or macroalbuminuria as defined by UACR > 50 mg/g or 5.7 mg/mmol.
- Diagnosed with T2DM with glucose control managed with any insulin and/or any oral therapy combination including metformin, SGLT2 inhibitor, thiazolidinedione, or acarbose where no major dose changes (eg, > 50% increase in dose) have occurred within the 4 weeks prior to the start of the run-in period. Participants taking sulfonylureas or glitinides may be randomised following a 4-week washout period of the sulfonylurea/glitinide.
- Haemoglobin A1c range of 6.5 % to 12.5% (inclusive) at screening
- Body mass index > 25 kg/m2 at screening or > 23 kg/m2 for participants enrolled in Japan
Exclusion Criteria:
- History or presence of significant medical or psychological conditions, including significant abnormalities in laboratory parameters or vital signs including ECG, which in the opinion of the investigator, would compromise the participant's safety or successful participation in the study.
- Receiving renal replacement therapy or expected to require it within 6 months of being randomised
- Renal transplant or on the waiting list for renal transplantation
- Received a 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
Received any of the following medications within the specified time frame prior to the start of the study (Visit 2):
- Aspirin (acetylsalicylic acid) at a dose greater than 150 mg once daily and within the last 3 days prior to the start of the run-in period (Visit 2)
- Paracetamol (acetaminophen) or paracetamol-containing preparations at a total daily dose of greater than 3000 mg and within the last 3 days prior to the start of the run-in period (Visit 2)
- Ascorbic acid (vitamin C) supplements at a total daily dose of greater than 1000 mg and within the last 3 days prior to the start of the run-in period (Visit 2)
- Participation in another clinical study with an investigational product administered in the last 30 days or 5 half-lives of the drug, if known (whichever is longer)
- Participants with a known severe allergy/hypersensitivity to any of the proposed study interventions or excipients of the product
- Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss) or recent episodes of severe hypoglycaemia
- Type 1 diabetes mellitus (T1DM), history of diabetic ketoacidosis, or clinical suspicion of T1DM
- Participants with recent acute or subacute renal function deterioration
- Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper gastrointestinal tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
- History of acute or chronic pancreatitis
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:
- Aspartate transaminase (AST) ≥ 3 × upper limit of normal (ULN)
- Alanine transaminase (ALT) ≥ 3 × ULN
- Total bilirubin ≥ 2 × ULN
Poorly controlled hypertension defined as:
- Systolic BP > 180 mm Hg
- Diastolic BP ≥ 90 mm Hg after 10 minutes of seated rest and confirmed by repeated measurement at screening. Participants who fail BP screening criteria may be considered for 24-hour ambulatory BP monitoring at the discretion of the investigator. Participants who maintain a mean 24-hour systolic BP ≤ 180 or diastolic BP < 90 mm Hg with a preserved nocturnal dip of > 15% will be considered eligible
- 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
- Decompensated heart failure or hospitalisation for heart failure in the 3 months prior to screening or symptoms consistent with New York Heart Association heart failure Class III/IV
- Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Placebo
Placebo administered subcutaneously
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Placebo administered subcutaneously
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Experimental: Cotadutide 100 micrograms
Cotadutide 100 micrograms administered subcutaneously
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Cotadutide 100 micrograms administered subcutaneously
Other Names:
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Experimental: Cotadutide 300 micrograms
Cotadutide 300 micrograms administered subcutaneously
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Cotadutide 300 micrograms administered subcutaneously
Other Names:
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Experimental: Cotadutide 600 micrograms
Cotadutide 600 micrograms administered subcutaneously
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Cotadutide 600 micrograms administered subcutaneously
Other Names:
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Active Comparator: Semaglutide
Semaglutide 1.0 miligrams administered subcutaneously
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Semaglutide 1.0 miligrams administered subcutaneously
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 14 weeks
Time Frame: 14 weeks
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Change and percentage change in UACR versus placebo from baseline to the end of 14 weeks of dosing
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14 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 14 weeks
Time Frame: 14 weeks
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Change and percentage change in UACR versus placebo from baseline to the end of 14 weeks of dosing
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14 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 26 weeks
Time Frame: 26 weeks
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Change and percentage change in UACR versus placebo from baseline to the end of 26 weeks of dosing
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo on HbA1c and fasting glucose
Time Frame: 26 weeks
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Change in HbA1c versus placebo from baseline to the end of 14 and 26 weeks of dosing
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo on HbA1c and fasting glucose
Time Frame: 26 weeks
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Change in fasting glucose from baseline versus placebo after 14 and 26 weeks of dosing
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo on glucose levels as measured by CGM
Time Frame: 26 weeks
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Change in 10-day average glucose levels as measured by CGM versus placebo from baseline to the end of 14 and 26 weeks of dosing
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo on glucose levels as measured by CGM
Time Frame: 26 weeks
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Change in percentage time spent in hyperglycaemia (> 10 mmol/L), target range (3.9 -10 mmol/L), hypoglycaemia (< 3.9 mmol/L), and clinically significant hypoglycaemia (< 3.0 mmol/l) over 10 days as measured by CGM versus placebo from baseline to the end of 14 and 26 weeks of dosing
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo on body weight
Time Frame: 26 weeks
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Change and percentage change in body weight versus placebo from baseline to the end of 14 and 26 weeks of dosing
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo on body weight
Time Frame: 26 weeks
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Proportion of participants achieving ≥ 5% and ≥ 10% body weight loss versus placebo from baseline to the end of 14 and 26 weeks of dosing
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26 weeks
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To evaluate the immunogenicity profile of cotadutide compared to placebo
Time Frame: 30 weeks
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ADAs during the titration treatment period and follow-up period
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30 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE V4.0
Time Frame: 26 weeks
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Safety and tolerability of daily SC doses of Cotadutide by assessment of the following using CTCAE V4.0:
The number of Treatment Emergent Adverse events (TEAEs)
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of Treatment Emergent Serious Adverse Events (TESAEs) as assessed by CTCAE V4.0
Time Frame: 26 weeks
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Safety and tolerability of daily SC doses of Cotadutide by assessment of the following using CTCAE V4.0:
The number of Treatment-Emergent Serious Adverse Events (TESAEs)
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of Treatment Emergent Adverse Events of Special Interest (AESIs) as assessed by CTCAE V4.0
Time Frame: 26 weeks
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Safety and tolerability of daily SC doses of Cotadutide by assessment of the following using CTCAE V4.0:
The number of Treatment Emergent Adverse Events of Special Interest (AESIs)
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in blood pressure
Time Frame: 26 weeks
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Number of subjects with clinically significant changes in systolic and diastolic blood pressure (mmHg)
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in blood pressure
Time Frame: 26 weeks
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Percentage of subjects with clinically significant changes in systolic and diastolic blood pressure (mmHg)
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in heart rate
Time Frame: 26 weeks
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Number of subjects with clinically significant changes in heart rate
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in heart rate
Time Frame: 26 weeks
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Percentage of subjects with clinically significant changes in heart rate
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in haematology and clinical chemistry parameters
Time Frame: 26 weeks
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Percentage of subjects with clinically significant changes in in haematology and or clinical chemistry parameters
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in haematology and clinical chemistry parameters
Time Frame: 26 weeks
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Number of subjects with clinically significant changes in in haematology and or clinical chemistry parameters
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in ECG
Time Frame: 26 weeks
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Number of subjects with an ECG determined to be abnormal and clinically significant
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26 weeks
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To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in ECG
Time Frame: 26 weeks
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Percentage of subjects with an ECG determined to be abnormal and clinically significant
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26 weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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To characterise the exposure of cotadutide in participants who have CKD with T2DM
Time Frame: 26 weeks
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Cotadutide PK exposure (eg, concentrations predose and 4 hours postdose) at steady state.
Cotadutide plasma concentrations prior to injection and 4 hours post injection at steady state at different dose levels and different visits over 26 weeks.
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to semaglutide on UACR and compared to placebo and semaglutide on urine albumin and urinary creatinine
Time Frame: 26 weeks
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to semaglutide on HbA1c and fasting glucose
Time Frame: 26 weeks
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to semaglutide on body weight
Time Frame: 26 weeks
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo and semaglutide on blood pressure
Time Frame: 26 weeks
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• Change in SBP, DBP versus placebo and/or semaglutide from baseline to the end of 14 and 26 weeks dosing
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo and semaglutide on pulse rate
Time Frame: 26 weeks
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• Change in pulse rate versus placebo and/or semaglutide from baseline to the end of 14 and 26 weeks dosing
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26 weeks
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To assess the effects of cotadutide at different dose levels compared to placebo and semaglutide on rate pressure product
Time Frame: 26 weeks
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• Absolute change in rate pressure product versus placebo and/or semaglutide from baseline to the end of 14 and 26 weeks dosing
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26 weeks
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- D5676C00001
- 2020-000255-12 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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