Phase 2b Study of Cotadutide in Participants Who Have Chronic Kidney Disease with Type 2 Diabetes Mellitus
- Conditions
- Chronic Kidney Disease with Type 2 Diabetes MellitusMedDRA version: 23.1Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disordersMedDRA version: 21.1Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2020-000255-12-DE
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 225
1/ Male and female subjects = 18 and = 79 years of age at the time of signing the informed consent.
2/ Estimated glomerular filtration rate = 20 to < 90 mL/min/1.73 m2 determined at the screening visit or a documented occurrence in their medical history at least 3 months prior to randomisation.
3/ Receiving background standard of care treatment for renal disease and/or T2DM and being treated according to locally recognised guidelines, as appropriate.
4/ 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.
5/ Micro- or macroalbuminuria as defined by UACR > 50 mg/g or 5.7 mg/mmol.
6/ Diagnosed with T2DM with glucose control managed with any insulin and/or any oral therapy combination
7/ Haemoglobin A1c range of 6.5 % to 12.5% (inclusive) at screening
8/ Body mass index > 25 kg/m^2 at screening or > 23 kg/m^2 for participants enrolled in Japan
9/ Negative pregnancy test at screening (serum only) and randomisation (serum or urine) for female participants of childbearing potential and must not be breastfeeding.
10/ Female participants of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study to 5 weeks after the last dose.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 113
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 112
1/ History or presence of significant medical or psychological conditions, including significant abnormalities in laboratory parameters or vital signs
2/ Receiving renal replacement therapy or expected to require it within 6 months of being randomised
3/ Renal transplant or on the waiting list for renal transplantation
4/ 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
5/ Received any of the following medications within the specified time frame prior to the start of the study (Visit 2):
(a) 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)
(b) 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)
(c) 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)
6/ 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)
7/ Participants with a known severe allergy/hypersensitivity to any of the proposed study interventions or excipients of the product.
8/ Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss) or recent episodes of severe hypoglycaemia in the prior 3 months
9/ Type 1 diabetes mellitus (T1DM), history of diabetic ketoacidosis, or clinical suspicion of T1DM (eg, undetectable levels of C peptide and positive tests for antibodies indicative of T1DM)
10/ Participants with recent acute or subacute renal function deterioration (eg, participants with large fluctuations of creatinine values documented within the 3 months prior to screening)
11/ Significant inflammatory bowel disease, gastroparesis, or other severe disease or surgery affecting the upper gastrointestinal tract (including weight-reducing surgery and procedures) that may affect gastric emptying or could affect the interpretation of safety and tolerability data
12/ History of acute or chronic pancreatitis
13/ 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:
(a)Aspartate transaminase (AST) = 3 × upper limit of normal (ULN)
(b)Alanine transaminase (ALT) = 3 × ULN
(c)Total bilirubin = 2 × ULN
14Poorly controlled hypertension defined as:
(a)Systolic blood pressure (SBP) > 160 mm Hg
(b)Diastolic blood pressure (DBP) = 90 mm Hg
- After 10 minutes of seated rest or semi-supine and confirmed by repeated measurement at screening.
- Participants who fail blood pressure screening criteria may be considered for 24-hour ambulatory blood pressure monitoring at the discretion of the investigator. Participants who maintain a mean 24-hour SBP = 160 or DBP < 90 mm Hg with a preserved nocturnal dip of > 15% will be considered eligible
15/ 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 u
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 14 weeks;Secondary Objective: - To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 26 weeks <br><br>- To assess the effects of cotadutide at different dose levels compared to placebo on HbA1c and fasting glucose<br><br>- To assess the effects of cotadutide at different dose levels compared to placebo on glucose levels as measured by CGM<br><br>- To assess the effects of cotadutide at different dose levels compared to placebo on body weight <br><br>- To evaluate the immunogenicity profile of cotadutide compared to placebo;Primary end point(s): Change and percentage change in UACR versus placebo from baseline to the end of 14 weeks of dosing;Timepoint(s) of evaluation of this end point: baseline to the end of 14 weeks of dosing
- Secondary Outcome Measures
Name Time Method