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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04515849




Registration number
NCT04515849
Ethics application status
Date submitted
6/07/2020
Date registered
17/08/2020
Date last updated
3/05/2021

Titles & IDs
Public title
A Study of Cotadutide in Participants Who Have Chronic Kidney Disease With Type 2 Diabetes Mellitus
Scientific title
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
Secondary ID [1] 0 0
2020-000255-12
Secondary ID [2] 0 0
D5676C00001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 0 0
Chronic Kidney Diseases 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Renal and Urogenital 0 0 0 0
Other renal and urogenital disorders
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cotadutide 100 micrograms
Treatment: Drugs - Cotadutide 300 micrograms
Treatment: Drugs - Cotadutide 600 micrograms
Treatment: Drugs - Semaglutide
Treatment: Drugs - Placebo

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


Treatment: Drugs: Cotadutide 100 micrograms
Cotadutide 100 micrograms administered subcutaneously

Treatment: Drugs: Cotadutide 300 micrograms
Cotadutide 300 micrograms administered subcutaneously

Treatment: Drugs: Cotadutide 600 micrograms
Cotadutide 600 micrograms administered subcutaneously

Treatment: Drugs: Semaglutide
Semaglutide 1.0 miligrams administered subcutaneously

Treatment: Drugs: Placebo
Placebo administered subcutaneously

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 14 weeks - Change and percentage change in UACR versus placebo from baseline to the end of 14 weeks of dosing
Timepoint [1] 0 0
14 weeks
Secondary outcome [1] 0 0
To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 14 weeks - Change and percentage change in UACR versus placebo from baseline to the end of 14 weeks of dosing
Timepoint [1] 0 0
14 weeks
Secondary outcome [2] 0 0
To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 26 weeks - Change and percentage change in UACR versus placebo from baseline to the end of 26 weeks of dosing
Timepoint [2] 0 0
26 weeks
Secondary outcome [3] 0 0
To assess the effects of cotadutide at different dose levels compared to placebo on HbA1c and fasting glucose - Change in HbA1c versus placebo from baseline to the end of 14 and 26 weeks of dosing
Timepoint [3] 0 0
26 weeks
Secondary outcome [4] 0 0
To assess the effects of cotadutide at different dose levels compared to placebo on HbA1c and fasting glucose - Change in fasting glucose from baseline versus placebo after 14 and 26 weeks of dosing
Timepoint [4] 0 0
26 weeks
Secondary outcome [5] 0 0
To assess the effects of cotadutide at different dose levels compared to placebo on glucose levels as measured by CGM - 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
Timepoint [5] 0 0
26 weeks
Secondary outcome [6] 0 0
To assess the effects of cotadutide at different dose levels compared to placebo on glucose levels as measured by CGM - 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
Timepoint [6] 0 0
26 weeks
Secondary outcome [7] 0 0
To assess the effects of cotadutide at different dose levels compared to placebo on body weight - Change and percentage change in body weight versus placebo from baseline to the end of 14 and 26 weeks of dosing
Timepoint [7] 0 0
26 weeks
Secondary outcome [8] 0 0
To assess the effects of cotadutide at different dose levels compared to placebo on body weight - Proportion of participants achieving = 5% and = 10% body weight loss versus placebo from baseline to the end of 14 and 26 weeks of dosing
Timepoint [8] 0 0
26 weeks
Secondary outcome [9] 0 0
To evaluate the immunogenicity profile of cotadutide compared to placebo - ADAs during the titration treatment period and follow-up period
Timepoint [9] 0 0
30 weeks
Secondary outcome [10] 0 0
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 - 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)
Timepoint [10] 0 0
26 weeks
Secondary outcome [11] 0 0
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 - 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)
Timepoint [11] 0 0
26 weeks
Secondary outcome [12] 0 0
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 - 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)
Timepoint [12] 0 0
26 weeks
Secondary outcome [13] 0 0
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in blood pressure - Number of subjects with clinically significant changes in systolic and diastolic blood pressure (mmHg)
Timepoint [13] 0 0
26 weeks
Secondary outcome [14] 0 0
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in blood pressure - Percentage of subjects with clinically significant changes in systolic and diastolic blood pressure (mmHg)
Timepoint [14] 0 0
26 weeks
Secondary outcome [15] 0 0
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in heart rate - Number of subjects with clinically significant changes in heart rate
Timepoint [15] 0 0
26 weeks
Secondary outcome [16] 0 0
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in heart rate - Percentage of subjects with clinically significant changes in heart rate
Timepoint [16] 0 0
26 weeks
Secondary outcome [17] 0 0
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in haematology and clinical chemistry parameters - Percentage of subjects with clinically significant changes in in haematology and or clinical chemistry parameters
Timepoint [17] 0 0
26 weeks
Secondary outcome [18] 0 0
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in haematology and clinical chemistry parameters - Number of subjects with clinically significant changes in in haematology and or clinical chemistry parameters
Timepoint [18] 0 0
26 weeks
Secondary outcome [19] 0 0
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in ECG - Number of subjects with an ECG determined to be abnormal and clinically significant
Timepoint [19] 0 0
26 weeks
Secondary outcome [20] 0 0
To evaluate the safety and tolerability of cotadutide compared to placebo by assessment of changes in ECG - Percentage of subjects with an ECG determined to be abnormal and clinically significant
Timepoint [20] 0 0
26 weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
79 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Box Hill
Recruitment hospital [2] 0 0
Research Site - Elizabeth Vale
Recruitment hospital [3] 0 0
Research Site - Fitzroy
Recruitment hospital [4] 0 0
Research Site - Heidelberg
Recruitment hospital [5] 0 0
Research Site - Melbourne
Recruitment hospital [6] 0 0
Research Site - Merewether
Recruitment hospital [7] 0 0
Research Site - Oaklands Park
Recruitment hospital [8] 0 0
Research Site - Wollongong
Recruitment hospital [9] 0 0
Research Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
2291 - Merewether
Recruitment postcode(s) [7] 0 0
5046 - Oaklands Park
Recruitment postcode(s) [8] 0 0
2500 - Wollongong
Recruitment postcode(s) [9] 0 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
British Columbia
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
Germany
State/province [4] 0 0
Berlin
Country [5] 0 0
Germany
State/province [5] 0 0
Dortmund
Country [6] 0 0
Germany
State/province [6] 0 0
Dusseldorf
Country [7] 0 0
Germany
State/province [7] 0 0
Essen
Country [8] 0 0
Germany
State/province [8] 0 0
Kassel
Country [9] 0 0
Germany
State/province [9] 0 0
Ludwigsplatz
Country [10] 0 0
Germany
State/province [10] 0 0
Magdeburg
Country [11] 0 0
Germany
State/province [11] 0 0
Mainz
Country [12] 0 0
Germany
State/province [12] 0 0
München
Country [13] 0 0
Germany
State/province [13] 0 0
Münster
Country [14] 0 0
Germany
State/province [14] 0 0
Riesa
Country [15] 0 0
Germany
State/province [15] 0 0
Saint Ingbert
Country [16] 0 0
Japan
State/province [16] 0 0
Arakawa-ku
Country [17] 0 0
Japan
State/province [17] 0 0
Chitose-shi
Country [18] 0 0
Japan
State/province [18] 0 0
Fujisawa-shi
Country [19] 0 0
Japan
State/province [19] 0 0
Kamakura-shi
Country [20] 0 0
Japan
State/province [20] 0 0
Obihiro-shi
Country [21] 0 0
Japan
State/province [21] 0 0
Sapporo-shi
Country [22] 0 0
Japan
State/province [22] 0 0
Shinjyuku-ku
Country [23] 0 0
New Zealand
State/province [23] 0 0
Auckland
Country [24] 0 0
New Zealand
State/province [24] 0 0
Christchurch
Country [25] 0 0
New Zealand
State/province [25] 0 0
Grafton
Country [26] 0 0
New Zealand
State/province [26] 0 0
Havelock North
Country [27] 0 0
New Zealand
State/province [27] 0 0
New Plymouth
Country [28] 0 0
New Zealand
State/province [28] 0 0
Tauranga
Country [29] 0 0
New Zealand
State/province [29] 0 0
Wellington
Country [30] 0 0
Poland
State/province [30] 0 0
Bialystok
Country [31] 0 0
Poland
State/province [31] 0 0
Grodzisk Mazowiecki
Country [32] 0 0
Poland
State/province [32] 0 0
Krakow
Country [33] 0 0
Poland
State/province [33] 0 0
Kraków
Country [34] 0 0
Poland
State/province [34] 0 0
Lublin
Country [35] 0 0
Poland
State/province [35] 0 0
New York
Country [36] 0 0
Poland
State/province [36] 0 0
Poznan
Country [37] 0 0
Poland
State/province [37] 0 0
Skierniewice
Country [38] 0 0
Poland
State/province [38] 0 0
Warszawa
Country [39] 0 0
Poland
State/province [39] 0 0
Wierzchoslawice
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Cordoba
Country [42] 0 0
Spain
State/province [42] 0 0
La Coruna
Country [43] 0 0
Spain
State/province [43] 0 0
Lérida
Country [44] 0 0
Spain
State/province [44] 0 0
Madrid
Country [45] 0 0
Spain
State/province [45] 0 0
Majadahonda
Country [46] 0 0
Spain
State/province [46] 0 0
Malaga
Country [47] 0 0
Spain
State/province [47] 0 0
Palma de Mallorca
Country [48] 0 0
Spain
State/province [48] 0 0
Palma
Country [49] 0 0
Spain
State/province [49] 0 0
Pozuelo de Alarcón
Country [50] 0 0
Spain
State/province [50] 0 0
Sevilla
Country [51] 0 0
Spain
State/province [51] 0 0
Valencia
Country [52] 0 0
Spain
State/province [52] 0 0
Vitoria
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Dundee
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Liverpool
Country [55] 0 0
United Kingdom
State/province [55] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT04515849
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04515849