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

A Phase 2b, study to measure the effect of Cotadutide at different doses versus placebo or comparator (semaglutide) in participants who have Chronic Kidney Disease with Type 2 Diabetes Mellitus.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Diseases; Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Cotadutide 100 micrograms; Drug: Cotadutide 300 micrograms; Drug: Cotadutide 600 micrograms; Drug: Placebo; Drug: Semaglutide

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: Interventional
• Enrollment (Actual): 248
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Research Site
  • Elizabeth Vale, Australia, 5112
    • Research Site
  • Fitzroy, Australia, 3065
    • Research Site
  • Heidelberg, Australia, 3084
    • Research Site
  • Melbourne, Australia, 3004
    • Research Site
  • Merewether, Australia, 2291
    • Research Site
  • Oaklands Park, Australia, 5046
    • Research Site
  • Wollongong, Australia, 2500
    • Research Site
  • Woolloongabba, Australia, 4102
    • Research Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Y 3W2
      • Research Site
  • Ontario
    • Barrie, Ontario, Canada, L4N 7L3
      • Research Site
    • Brampton, Ontario, Canada, L6S 0C6
      • Research Site
    • Concord, Ontario, Canada, L4K 4M2
      • Research Site
    • Etobicoke, Ontario, Canada, M9R 4E1
      • Research Site
    • Oakville, Ontario, Canada, L6M 1M1
      • Research Site
    • Oshawa, Ontario, Canada, L1G 2B9
      • Research Site
    • Ottawa, Ontario, Canada, K2J 0V2
      • Research Site
    • Toronto, Ontario, Canada, M4G 3E8
      • Research Site
    • Toronto, Ontario, Canada, M5G 2C4
      • Research Site
    • Waterloo, Ontario, Canada, N2T 0C1
      • Research Site
  • Quebec
    • Laval, Quebec, Canada, H7T 2P5
      • Research Site
    • Montreal, Quebec, Canada, H4A 2C6
      • Research Site
• Germany
  • Berlin, Germany, 10409
    • Research Site
  • Berlin, Germany, 10437
    • Research Site
  • Berlin, Germany, 10789
    • Research Site
  • Dortmund, Germany, 44137
    • Research Site
  • Dusseldorf, Germany, 40210
    • Research Site
  • Essen, Germany, 45359
    • Research Site
  • Kassel, Germany, 34121
    • Research Site
  • Ludwigshafen, Germany, 67059
    • Research Site
  • Magdeburg, Germany, 39120
    • Research Site
  • Mainz, Germany, 55116
    • Research Site
  • München, Germany, 81241
    • Research Site
  • Münster, Germany, 48153
    • Research Site
  • Münster, Germany, 48145
    • Research Site
  • Riesa, Germany, 01587
    • Research Site
  • Sankt Ingbert, Germany, 66386
    • Research Site
• Japan
  • Arakawa-ku, Japan, 116-0012
    • Research Site
  • Chitose-shi, Japan, 066-0032
    • Research Site
  • Fujisawa-shi, Japan, 251-0041
    • Research Site
  • Kamakura-shi, Japan, 247-8533
    • Research Site
  • Obihiro-shi, Japan, 080-0848
    • Research Site
  • Sapporo-shi, Japan, 060-0062
    • Research Site
  • Shinjyuku-ku, Japan, 160-0022
    • Research Site
• New Zealand
  • Auckland, New Zealand, 2025
    • Research Site
  • Auckland, New Zealand, ?0620
    • Research Site
  • Christchurch, New Zealand, 8011
    • Research Site
  • Grafton, New Zealand, 1010
    • Research Site
  • Havelock North, New Zealand, 4130
    • Research Site
  • New Plymouth, New Zealand, 4310
    • Research Site
  • Tauranga, New Zealand, 3110
    • Research Site
  • Wellington, New Zealand, 6021
    • Research Site
• Poland
  • Białystok, Poland, 15-435
    • Research Site
  • Grodzisk Mazowiecki, Poland, 05-825
    • Research Site
  • Katowice, Poland, 40-081
    • Research Site
  • Krakow, Poland, 30-033
    • Research Site
  • Krakow, Poland, 31-261
    • Research Site
  • Kraków, Poland, 31-530
    • Research Site
  • Lublin, Poland, 20064
    • Research Site
  • Poznań, Poland, 61-655
    • Research Site
  • Skierniewice, Poland, 96-100
    • Research Site
  • Warszawa, Poland, 01-518
    • Research Site
  • Warszawa, Poland, 02-507
    • Research Site
  • Warszawa, Poland, 00-660
    • Research Site
  • Wierzchosławice, Poland, 33-122
    • Research Site
• Spain
  • Barcelona, Spain, 08036
    • Research Site
  • Cordoba, Spain, 14004
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08907
    • Research Site
  • La Coruna, Spain, 15006
    • Research Site
  • Lérida, Spain, 25198
    • Research Site
  • Madrid, Spain, 28006
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Malaga, Spain, 29010
    • Research Site
  • Palma, Spain, 07198
    • Research Site
  • Palma de Mallorca, Spain, 07010
    • Research Site
  • Pozuelo de Alarcón, Spain, 28223
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
  • Sevilla, Spain, 41003
    • Research Site
  • Valencia, Spain, 46009
    • Research Site
  • Vitoria, Spain, 01009
    • Research Site
• United Kingdom
  • Dundee, United Kingdom, DD1 9SY
    • Research Site
  • Liverpool, United Kingdom, L9 7AL
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

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):

  1. 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)
  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)
  3. 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:

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

• Poorly controlled hypertension defined as:

  1. Systolic BP > 180 mm Hg
  2. 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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo administered subcutaneously	Drug: Placebo; Placebo administered subcutaneously
Experimental: Cotadutide 100 micrograms; Cotadutide 100 micrograms administered subcutaneously	Drug: Cotadutide 100 micrograms; Cotadutide 100 micrograms administered subcutaneously; Other Names: MEDI0382
Experimental: Cotadutide 300 micrograms; Cotadutide 300 micrograms administered subcutaneously	Drug: Cotadutide 300 micrograms; Cotadutide 300 micrograms administered subcutaneously; Other Names: MEDI0382
Experimental: Cotadutide 600 micrograms; Cotadutide 600 micrograms administered subcutaneously	Drug: Cotadutide 600 micrograms; Cotadutide 600 micrograms administered subcutaneously; Other Names: MEDI0382
Active Comparator: Semaglutide; Semaglutide 1.0 miligrams administered subcutaneously	Drug: Semaglutide; Semaglutide 1.0 miligrams administered subcutaneously; Other Names: Ozempic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks	Percentage change in UACR of cotadutide at different dose levels compared to placebo after 14 weeks. Efficacy endpoints for cotadutide vs. semaglutide are exploratory and are therefore excluded.	Baseline to the end of 14 weeks of dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks	Percentage change in UACR of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks. Efficacy endpoints for cotadutide vs. semaglutide are exploratory and are therefore excluded.	Baseline to end of 26 weeks of dosing
Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing	Percentage change in body weight of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing.	Baseline to end of 14 weeks of dosing
Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing	Percentage change in body weight of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing	Baseline to end of 26 weeks of dosing
Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of Dosing	Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing	Baseline to end of 14 weeks of dosing
Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of Dosing	Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing	Baseline to end of 26 weeks of dosing
Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing	Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks	Baseline to end of 14 weeks of dosing
Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing	Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks	Baseline to end of 26 weeks of dosing
Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing	Absolute change in 10-day average glucose of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing	Baseline to end of 14 weeks of dosing
Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing	Absolute change in 10-day average glucose of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing	Baseline to end of 26 weeks of dosing
Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing	Percentage change in 10-day percentage time spent in hyperglycaemia of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks	Baseline to 14 weeks of dosing
Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing	Percentage change in 10-day percentage time spent in hyperglycaemia of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks	Baseline to 26 weeks of dosing

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterise the exposure of cotadutide in participants who have CKD with T2DM	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.	26 weeks
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	Change and percentage change in UACR versus semaglutide from baseline to the end of 14 and 26 weeks dosing; Change and percentage change in urine albumin versus placebo and semaglutide from baseline to the end of 14 and 26 weeks dosing; Change and percentage change in urinary creatinine versus placebo and semaglutide from baseline to the end of 14 and 26 weeks dosing	26 weeks
To assess the effects of cotadutide at different dose levels compared to semaglutide on HbA1c and fasting glucose	Change in HbA1c versus semaglutide from baseline to the end of 14 and 26 weeks dosing; Change in fasting glucose versus semaglutide from baseline to the end of 14 and 26 weeks dosing	26 weeks
To assess the effects of cotadutide at different dose levels compared to semaglutide on body weight	Change and percentage change in body weight versus semaglutide from baseline to the end of 14 and 26 weeks dosing; Proportion of participants achieving ≥ 5% and ≥ 10% body weight loss versus semaglutide from baseline to the end of 14 and 26 weeks dosing	26 weeks
To assess the effects of cotadutide at different dose levels compared to placebo and semaglutide on blood pressure	• Change in SBP, DBP versus placebo and/or semaglutide from baseline to the end of 14 and 26 weeks dosing	26 weeks
To assess the effects of cotadutide at different dose levels compared to placebo and semaglutide on pulse rate	• Change in pulse rate versus placebo and/or semaglutide from baseline to the end of 14 and 26 weeks dosing	26 weeks
To assess the effects of cotadutide at different dose levels compared to placebo and semaglutide on rate pressure product	• Absolute change in rate pressure product versus placebo and/or semaglutide from baseline to the end of 14 and 26 weeks dosing	26 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• Selvarajah V, Robertson D, Hansen L, Jermutus L, Smith K, Coggi A, Sanchez J, Chang YT, Yu H, Parkinson J, Khan A, Chung HS, Hess S, Dumas R, Duck T, Jolly S, Elliott TG, Baker J, Lecube A, Derwahl KM, Scott R, Morales C, Peters C, Goldenberg R, Parker VER, Heerspink HJL; study investigators. A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease. Kidney Int. 2024 Dec;106(6):1170-1180. doi: 10.1016/j.kint.2024.08.023. Epub 2024 Aug 31.

Helpful Links

• CSR Synopsis
• CSP Redacted
• SAP redacted

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2020
• Primary Completion (Actual): March 8, 2022
• Study Completion (Actual): March 8, 2022

Study Registration Dates

• First Submitted: July 6, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 6, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: T2DM; Diabetic Kidney Disease; Cotadutide; MEDI0382
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Glucose Metabolism Disorders; Renal Insufficiency; Diabetes Mellitus, Type 2; Diabetes Mellitus; Kidney Diseases; Renal Insufficiency, Chronic; Glucagon-Like Peptide-1 Receptor Agonists; Physiological Effects of Drugs; Hypoglycemic Agents; Semaglutide
• Other Study ID Numbers: D5676C00001; 2020-000255-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

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: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No