A Study of Cotadutide in Participants Who Have Chronic Kidney Disease With Type 2 Diabetes Mellitus

March 28, 2022 updated by: AstraZeneca

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

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)

247

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • 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
    • 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
      • Ottawa, Ontario, Canada, K2J 0V2
        • Research Site
      • Toronto, Ontario, Canada, M4G 3E8
        • Research Site
      • Waterloo, Ontario, Canada, N2J 3Z4
        • Research Site
    • Quebec
      • Laval, Quebec, Canada, H7T 2P5
        • Research Site
      • Montreal, Quebec, Canada, H4A 2C6
        • Research Site
      • Berlin, Germany, 10409
        • Research Site
      • Berlin, Germany, 10437
        • Research Site
      • Dortmund, Germany, 44137
        • Research Site
      • Dusseldorf, Germany, 40210
        • Research Site
      • Essen, Germany, 45359
        • 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
      • 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
      • 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
      • Tauranga, New Zealand, 3110
        • Research Site
      • Wellington, New Zealand, 6021
        • Research Site
      • Białystok, Poland, 15-435
        • Research Site
      • Krakow, Poland, 30-033
        • Research Site
      • Krakow, Poland, 31-261
        • Research Site
      • Lublin, Poland, 20064
        • Research Site
      • New York, Poland, 40-081
        • Research Site
      • Poznań, Poland, 61-655
        • Research Site
      • Warszawa, Poland, 02-507
        • Research Site
      • 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
      • Majadahonda, Spain, 28222
        • Research Site
      • Malaga, Spain, 29010
        • 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
      • London, United Kingdom, SE5 9RS
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 79 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
Placebo Comparator: Placebo
Placebo administered subcutaneously
Placebo administered subcutaneously
Experimental: Cotadutide 100 micrograms
Cotadutide 100 micrograms administered subcutaneously
Cotadutide 100 micrograms administered subcutaneously
Other Names:
  • MEDI0382
Experimental: Cotadutide 300 micrograms
Cotadutide 300 micrograms administered subcutaneously
Cotadutide 300 micrograms administered subcutaneously
Other Names:
  • MEDI0382
Experimental: Cotadutide 600 micrograms
Cotadutide 600 micrograms administered subcutaneously
Cotadutide 600 micrograms administered subcutaneously
Other Names:
  • MEDI0382
Active Comparator: Semaglutide
Semaglutide 1.0 miligrams administered subcutaneously
Semaglutide 1.0 miligrams administered subcutaneously
Other Names:
  • Ozempic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 14 weeks
Time Frame: 14 weeks
Change and percentage change in UACR versus placebo from baseline to the end of 14 weeks of dosing
14 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 14 weeks
Time Frame: 14 weeks
Change and percentage change in UACR versus placebo from baseline to the end of 14 weeks of dosing
14 weeks
To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 26 weeks
Time Frame: 26 weeks
Change and percentage change in UACR versus placebo from baseline to the end of 26 weeks of dosing
26 weeks
To assess the effects of cotadutide at different dose levels compared to placebo on HbA1c and fasting glucose
Time Frame: 26 weeks
Change in HbA1c versus placebo from baseline to the end of 14 and 26 weeks of dosing
26 weeks
To assess the effects of cotadutide at different dose levels compared to placebo on HbA1c and fasting glucose
Time Frame: 26 weeks
Change in fasting glucose from baseline versus placebo after 14 and 26 weeks of dosing
26 weeks
To assess the effects of cotadutide at different dose levels compared to placebo on glucose levels as measured by CGM
Time Frame: 26 weeks
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
26 weeks
To assess the effects of cotadutide at different dose levels compared to placebo on glucose levels as measured by CGM
Time Frame: 26 weeks
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
26 weeks
To assess the effects of cotadutide at different dose levels compared to placebo on body weight
Time Frame: 26 weeks
Change and percentage change in body weight versus placebo from baseline to the end of 14 and 26 weeks of dosing
26 weeks
To assess the effects of cotadutide at different dose levels compared to placebo on body weight
Time Frame: 26 weeks
Proportion of participants achieving ≥ 5% and ≥ 10% body weight loss versus placebo from baseline to the end of 14 and 26 weeks of dosing
26 weeks
To evaluate the immunogenicity profile of cotadutide compared to placebo
Time Frame: 30 weeks
ADAs during the titration treatment period and follow-up period
30 weeks
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
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)
26 weeks
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
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)
26 weeks
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
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)
26 weeks
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in blood pressure
Time Frame: 26 weeks
Number of subjects with clinically significant changes in systolic and diastolic blood pressure (mmHg)
26 weeks
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in blood pressure
Time Frame: 26 weeks
Percentage of subjects with clinically significant changes in systolic and diastolic blood pressure (mmHg)
26 weeks
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in heart rate
Time Frame: 26 weeks
Number of subjects with clinically significant changes in heart rate
26 weeks
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in heart rate
Time Frame: 26 weeks
Percentage of subjects with clinically significant changes in heart rate
26 weeks
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
Percentage of subjects with clinically significant changes in in haematology and or clinical chemistry parameters
26 weeks
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
Number of subjects with clinically significant changes in in haematology and or clinical chemistry parameters
26 weeks
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in ECG
Time Frame: 26 weeks
Number of subjects with an ECG determined to be abnormal and clinically significant
26 weeks
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in ECG
Time Frame: 26 weeks
Percentage of subjects with an ECG determined to be abnormal and clinically significant
26 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
To characterise the exposure of cotadutide in participants who have CKD with T2DM
Time Frame: 26 weeks
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
Time Frame: 26 weeks
  • 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
Time Frame: 26 weeks
  • 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
Time Frame: 26 weeks
  • 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
Time Frame: 26 weeks
• 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
Time Frame: 26 weeks
• 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
Time Frame: 26 weeks
• 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

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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 29, 2022

Last Update Submitted That Met QC Criteria

March 28, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

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
  • Statistical Analysis Plan (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

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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