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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04515849
Ethics application status
Date submitted
6/07/2020
Date registered
17/08/2020

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
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
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
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
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
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
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
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
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
Timepoint [8] 0 0
26 weeks
Secondary outcome [9] 0 0
To evaluate the immunogenicity profile of cotadutide compared to placebo
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
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
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
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
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
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
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
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
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
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
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
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
Sex
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
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/08/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/03/2022
Sample size
Target
Accrual to date
Final
247
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
Ludwigshafen
Country [9] 0 0
Germany
State/province [9] 0 0
Magdeburg
Country [10] 0 0
Germany
State/province [10] 0 0
Mainz
Country [11] 0 0
Germany
State/province [11] 0 0
München
Country [12] 0 0
Germany
State/province [12] 0 0
Münster
Country [13] 0 0
Japan
State/province [13] 0 0
Arakawa-ku
Country [14] 0 0
Japan
State/province [14] 0 0
Chitose-shi
Country [15] 0 0
Japan
State/province [15] 0 0
Fujisawa-shi
Country [16] 0 0
Japan
State/province [16] 0 0
Kamakura-shi
Country [17] 0 0
Japan
State/province [17] 0 0
Obihiro-shi
Country [18] 0 0
Japan
State/province [18] 0 0
Sapporo-shi
Country [19] 0 0
Japan
State/province [19] 0 0
Shinjyuku-ku
Country [20] 0 0
New Zealand
State/province [20] 0 0
Auckland
Country [21] 0 0
New Zealand
State/province [21] 0 0
Christchurch
Country [22] 0 0
New Zealand
State/province [22] 0 0
Grafton
Country [23] 0 0
New Zealand
State/province [23] 0 0
Havelock North
Country [24] 0 0
New Zealand
State/province [24] 0 0
Tauranga
Country [25] 0 0
New Zealand
State/province [25] 0 0
Wellington
Country [26] 0 0
Poland
State/province [26] 0 0
Bialystok
Country [27] 0 0
Poland
State/province [27] 0 0
Krakow
Country [28] 0 0
Poland
State/province [28] 0 0
Lublin
Country [29] 0 0
Poland
State/province [29] 0 0
New York
Country [30] 0 0
Poland
State/province [30] 0 0
Poznan
Country [31] 0 0
Poland
State/province [31] 0 0
Warszawa
Country [32] 0 0
Spain
State/province [32] 0 0
Barcelona
Country [33] 0 0
Spain
State/province [33] 0 0
Cordoba
Country [34] 0 0
Spain
State/province [34] 0 0
L'Hospitalet de Llobregat
Country [35] 0 0
Spain
State/province [35] 0 0
La Coruna
Country [36] 0 0
Spain
State/province [36] 0 0
Lérida
Country [37] 0 0
Spain
State/province [37] 0 0
Majadahonda
Country [38] 0 0
Spain
State/province [38] 0 0
Malaga
Country [39] 0 0
Spain
State/province [39] 0 0
Palma de Mallorca
Country [40] 0 0
Spain
State/province [40] 0 0
Pozuelo de Alarcón
Country [41] 0 0
Spain
State/province [41] 0 0
Sevilla
Country [42] 0 0
Spain
State/province [42] 0 0
Valencia
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04515849