Chronic Kidney Disease with Type 2 Diabetes Mellitus MedDRA version: 21.1 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 21.1 Level: PT Classification code 10067585 Term: Type 2 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: Cotadutide
Product Code: MEDI0382
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Cotadutide
CAS Number: 1686108-82-6
Current Sponsor code: MEDI0382
Co
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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 119 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 118
Exclusion criteria
Exclusion criteria: 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 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) which 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 14 Poorly controlled hypertension defined as: (a) Systolic BP > 180 mm Hg (b) 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 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 undergo these procedures at the time of screening 16/ Decompensated heart failure or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 14 weeks (Cohort 1 only);Secondary Objective: - To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 14 weeks (Cohort 2 only and Cohorts 1 and 2 combined) - To assess the effects of cotadutide at different dose levels compared to placebo on UACR after 26 weeks (Cohorts 1 and 2 separately and combined) - To assess the effects of cotadutide at different dose levels compared to placebo on HbA1c and fasting glucose (Cohorts 1 and 2 separately) - To assess the effects of cotadutide at different dose levels compared to placebo on glucose levels as measured by CGM (Cohorts 1 and 2 separately) - To assess the effects of cotadutide at different dose levels compared to placebo on body weight (Cohorts 1 and 2 separately) - To evaluate the immunogenicity profile of cotadutide compared to placebo (Cohorts 1 and 2 separately);Primary end point(s): Change and percentage change in UACR versus placebo from baseline to the end of 14 weeks of dosing in Cohort 1;Timepoint(s) of evaluation of this end point: baseline to the end of 14 weeks of dosing in Cohort 1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/ Change and percentage change in UACR versus placebo from baseline to the end of 14 weeks of dosing in Cohort 2 only and Cohorts 1 and 2 combined 2/ Change and percentage change in UACR versus placebo from baseline to the end of 26 weeks of dosing 3a/ Change in HbA1c versus placebo from baseline to the end of 14 and 26 weeks of dosing 3b/ Change in fasting glucose from baseline versus placebo after 14 and 26 weeks of dosing 4a/ 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 4b/ 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 5a/ Change and percentage change in body weight versus placebo from baseline to the end of 14 and 26 weeks of dosing 5b/ Proportion of participants achieving = 5% and = 10% body weight loss versus placebo from baseline to the end of 14 and 26 weeks of dosing 6/ ADAs during the titration treatment period and follow-up period;Timepoint(s) of evaluation of this end point: 1/ baseline to the end of 14 weeks of dosing in Cohort 2 only and Cohorts 1 and 2 combined 2/ baseline to the end of 26 weeks of dosing 3a/ baseline to the end of 14 and 26 weeks of dosing 3b/ from baseline versus placebo after 14 and 26 weeks of dosing 4a/ - 5b/ baseline to the end of 14 and 26 weeks of dosing 6/ during the titration treatment period and follow-up period | — |
Countries
Australia, Canada, Germany, Japan, New Zealand, Poland, Spain, United Kingdom
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed