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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

NCTNCT04515849 (opens ClinicalTrials.gov in a new tab)Other idD5676C00001Other id2020-000255-12

Overview

Status
Completed
Phase
Phase 2
Enrollment
248 participants (actual)
Sponsor
AstraZeneca · Industry
Design
Randomized · Double masking
Countries
8 countries

Australia, Canada, Germany, Japan, New Zealand, Poland, Spain, United Kingdom

Start
31 Aug 2020
Primary completion
8 Mar 2022
Completion
8 Mar 2022
First posted
17 Aug 2020
Last update posted
17 Jan 2025
Conditions
Type 2 Diabetes Mellitus · Chronic Kidney Diseases

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2020202120222023
  1. Ph 2

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

    NCT04515849

    31 Aug 2020 to 8 Mar 2022

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • Cotadutide 100 microgramsDrug
  • Cotadutide 300 microgramsDrug
  • Cotadutide 600 microgramsDrug
  • SemaglutideDrug
  • PlaceboDrug

Arms5

  • Experimental

    Cotadutide 100 micrograms

    Cotadutide 100 micrograms administered subcutaneously

  • Experimental

    Cotadutide 300 micrograms

    Cotadutide 300 micrograms administered subcutaneously

  • Experimental

    Cotadutide 600 micrograms

    Cotadutide 600 micrograms administered subcutaneously

  • Placebo comparator

    Placebo

    Placebo administered subcutaneously

  • Active comparator

    Semaglutide

    Semaglutide 1.0 miligrams administered subcutaneously

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks

    Time frame · Baseline to the end of 14 weeks of dosing

    Registry description

    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.

Secondary outcomes(11)
  1. Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks

    Time frame · Baseline to end of 26 weeks of dosing

    Registry description

    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.

  2. Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing

    Time frame · Baseline to end of 14 weeks of dosing

    Registry description

    Percentage change in body weight of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing.

  3. Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing

    Time frame · Baseline to end of 26 weeks of dosing

    Registry description

    Percentage change in body weight of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing

  4. Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of Dosing

    Time frame · Baseline to end of 14 weeks of dosing

    Registry description

    Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing

  5. Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of Dosing

    Time frame · Baseline to end of 26 weeks of dosing

    Registry description

    Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing

  6. Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing

    Time frame · Baseline to end of 14 weeks of dosing

    Registry description

    Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks

  7. Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing

    Time frame · Baseline to end of 26 weeks of dosing

    Registry description

    Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks

  8. Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing

    Time frame · Baseline to end of 14 weeks of dosing

    Registry description

    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

  9. Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing

    Time frame · Baseline to end of 26 weeks of dosing

    Registry description

    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

  10. Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing

    Time frame · Baseline to 14 weeks of dosing

    Registry description

    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

  11. Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing

    Time frame · Baseline to 26 weeks of dosing

    Registry description

    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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeGeometric least squares mean· Baseline to the end of 14 weeks of dosing

The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks

GroupValue (Percentage change)
Cotadutide 100 ug-10.96
Cotadutide 300 µg-40.47
Cotadutide 600 µg-44.60
Placebo ug4.60
Secondary and other outcome results(7)
Secondary outcomeGeometric least squares mean· Baseline to end of 26 weeks of dosing

Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks

GroupValue (Percentage change)
Cotadutide 100 ug-17.85
Cotadutide 300 µg-38.68
Cotadutide 600 µg-57.87
Placebo ug11.79
Secondary outcomeLeast squares mean· Baseline to end of 14 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

GroupValue (Percentage change)Spread
Cotadutide 100 ug-2.840.65
Cotadutide 300 µg-4.150.68
Cotadutide 600 µg-5.400.73
Placebo ug-1.610.66
Secondary outcomeLeast squares mean· Baseline to end of 26 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

GroupValue (Percentage change)Spread
Cotadutide 100 ug-2.600.89
Cotadutide 300 µg-5.450.92
Cotadutide 600 µg-7.350.99
Placebo ug-2.230.90
Secondary outcomeLeast squares mean· 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 14 of Dosing

GroupValue (Percent change)Spread
Cotadutide 100 µg-0.760.12
Cotadutide 300 µg-0.820.12
Cotadutide 600 µg-0.650.12
Placebo ug-0.080.12
Secondary outcomeLeast squares mean· 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 26 of Dosing

GroupValue (Percent change)Spread
Cotadutide 100 µg-0.920.11
Cotadutide 300 µg-0.920.11
Cotadutide 600 µg-0.890.11
Placebo ug-0.250.11
Secondary outcomeLeast squares mean· Baseline to end of 14 weeks of dosing

Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing

GroupValue (mmol/L)Spread
Cotadutide 100 ug-1.350.37
Cotadutide 300 µg-1.570.35
Cotadutide 600 µg-1.690.40
Placebo ug-0.540.37
Secondary outcomeLeast squares mean· Baseline to end of 26 weeks of dosing

Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing

GroupValue (mmol/L)Spread
Cotadutide 100 ug-1.780.36
Cotadutide 300 µg-1.760.37
Cotadutide 600 µg-1.570.39
Placebo ug-0.720.37

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Cotadutide 100 ugParticipants randomised to cotadutide 100 µg daily2 / 525 / 5243 / 52
Cotadutide 300 ugParticipants randomised to Cotadutide 300 ug daily0 / 495 / 4938 / 49
Cotadutide 600 ugParticipants randomised to Cotadutide 600 ug daily0 / 515 / 5138 / 51
Placebo ugParticipants randomised to placebo daily0 / 515 / 5138 / 51
Semaglutide 1 mgParticipants randomized to semaglutide 1 mg weekly0 / 455 / 4539 / 45

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies3

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Meta-analysis (pooled) · 2025

15 results

Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes.

Natale et al. 2025The Cochrane database of systematic reviewscited by 8

PMID 39963952PMC11834151DOI 10.1002/14651858.cd015849.pub2PUB-39963952

Rights unknown15 results

Indexing hint: Randomized controlled trial · 2025

Pharmacokinetic-pharmacodynamic (PK/PD) modelling of cotadutide effect in patients with chronic kidney disease and type 2 diabetes mellitus.

Yu et al. 2025British journal of clinical pharmacologycited by 1

PMID 40344607DOI 10.1002/bcp.70093PUB-40344607

Full text at the publisher
Publisher page

Indexing hint: Randomized controlled trial · 2024

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.

Selvarajah et al. 2024Kidney internationalcited by 34

PMID 39218393DOI 10.1016/j.kint.2024.08.023PUB-39218393

CC BY
Download PDF

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 79 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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