Chronic Kidney Diseases, Type 2 Diabetes Mellitus
Conditions
Keywords
MEDI0382, T2DM, Cotadutide, Diabetic Kidney Disease
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.
Detailed description
A Phase 2b randomised, double-blind, placebo-controlled and open-label active comparator study to evaluate the effect of Cotadutide at 100, 300 or 600 micrograms in participants who have Chronic Kidney Disease with Type 2 Diabetes Mellitus. The study plans to randomise approximately 225 subjects. Subjects will be randomised to receive double-blind Cotadutide or placebo at 100, 300 or 600 micrograms once daily for 26 weeks, or open-label semaglutide at 1.0 miligrams once a week for 26 weeks. Japanese participants will not be randomised to the semaglutide arm.
Interventions
DRUGSemaglutide
Semaglutide 1.0 miligrams administered subcutaneously
DRUGPlacebo
Placebo administered subcutaneously
DRUGCotadutide 100 micrograms
Cotadutide 100 micrograms administered subcutaneously
DRUGCotadutide 300 micrograms
Cotadutide 300 micrograms administered subcutaneously
DRUGCotadutide 600 micrograms
Cotadutide 600 micrograms administered subcutaneously
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks | Baseline to the end of 14 weeks of dosing | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | Baseline to end of 14 weeks of dosing | Percentage change in body weight of cotadutide at different dose levels compared to placebo from baseline to end of 14 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 | Baseline to end of 26 weeks of dosing | Percentage change in body weight of cotadutide at different dose levels compared to placebo from 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 14 of Dosing | Baseline to end of 14 weeks of dosing | Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from 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 26 of Dosing | Baseline to end of 26 weeks of dosing | Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing |
| Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing | Baseline to end of 14 weeks of dosing | Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks |
| Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks | Baseline to end of 26 weeks of dosing | 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. |
| Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | Baseline to end of 14 weeks of dosing | 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 |
| Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing | Baseline to end of 26 weeks of dosing | 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 |
| Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing | Baseline to 14 weeks of dosing | 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 |
| Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing | Baseline to 26 weeks of dosing | 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 |
| Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing | Baseline to end of 26 weeks of dosing | Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks |
Countries
Australia, Canada, Germany, Japan, New Zealand, Poland, Spain, United Kingdom
Participant flow
Recruitment details
This study was conducted at 79 participating sites in Canada, Australia, New Zealand, Japan, Germany, Poland, Spain and United Kingdom. First subject enrolled 31st August 2020. Last subject last visit: 8th March 2022.
Pre-assignment details
This is a parallel treatment, double-blind study with 5 arms: Cotadutide 100 mcg,300 mcg&600 mcg,placebo and an open-label semaglutide arm.Outcomes for the cotadutide arms vs. semaglutide were exploratory.Therefore semaglutide arm was excluded from Outcomes.248 patients were enrolled.The study had a 14-day run-in period during which participants followed by a 26-week treatment period and 28-day follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| Cotadutide 100 ug Participants randomised to cotadutide 100 µg daily | 52 |
| Cotadutide 300 ug Participants randomised to Cotadutide 300 ug daily | 49 |
| Cotadutide 600 ug Participants randomised to Cotadutide 600 ug daily | 51 |
| Placebo ug Participants randomised to placebo daily | 51 |
| Semaglutide 1 mg Participants randomized to semaglutide 1 mg weekly | 45 |
| Total | 248 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 2 |
| Overall Study | Death | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Other:family emergency | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other:randomised by error | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other:subject hasa to fly to greece for a family emergency and will not be back till 4-5 months | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cotadutide 100 ug | Total | Semaglutide 1 mg | Placebo ug | Cotadutide 600 ug | Cotadutide 300 ug |
|---|---|---|---|---|---|---|
| Age, Continuous | 67.2 Years STANDARD_DEVIATION 7.3 | 67.1 Years STANDARD_DEVIATION 7.8 | 67.0 Years STANDARD_DEVIATION 7.8 | 69.5 Years STANDARD_DEVIATION 7.3 | 66.1 Years STANDARD_DEVIATION 7.4 | 65.7 Years STANDARD_DEVIATION 8.8 |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized ASIAN | 10 Participants | 45 Participants | 2 Participants | 10 Participants | 13 Participants | 10 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 2 Participants | 5 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 2 Participants | 4 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized OTHER | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized WHITE | 38 Participants | 190 Participants | 41 Participants | 39 Participants | 36 Participants | 36 Participants |
| Sex: Female, Male Female | 9 Participants | 47 Participants | 12 Participants | 13 Participants | 10 Participants | 3 Participants |
| Sex: Female, Male Male | 43 Participants | 201 Participants | 33 Participants | 38 Participants | 41 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 52 | 0 / 49 | 0 / 51 | 0 / 51 | 0 / 45 |
| other Total, other adverse events | 43 / 52 | 38 / 49 | 38 / 51 | 38 / 51 | 39 / 45 |
| serious Total, serious adverse events | 5 / 52 | 5 / 49 | 5 / 51 | 5 / 51 | 5 / 45 |
Outcome results
Primary
The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks
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.
Time frame: Baseline to the end of 14 weeks of dosing
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Cotadutide 100 ug | The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks | -10.96 Percentage change |
| Cotadutide 300 µg | The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks | -40.47 Percentage change |
| Cotadutide 600 µg | The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks | -44.60 Percentage change |
| Placebo ug | The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks | 4.60 Percentage change |
Secondary
Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing
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
Time frame: Baseline to end of 14 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | -1.556 mmol/L | Standard Error 0.32 |
| Cotadutide 300 µg | Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | -1.478 mmol/L | Standard Error 0.337 |
| Cotadutide 600 µg | Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | -1.269 mmol/L | Standard Error 0.334 |
| Placebo ug | Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | -0.440 mmol/L | Standard Error 0.311 |
Secondary
Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing
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
Time frame: Baseline to end of 26 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing | -1.735 mmol/L | Standard Error 0.307 |
| Cotadutide 300 µg | Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing | -1.446 mmol/L | Standard Error 0.334 |
| Cotadutide 600 µg | Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing | -1.118 mmol/L | Standard Error 0.321 |
| Placebo ug | Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing | -0.273 mmol/L | Standard Error 0.29 |
Secondary
Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing
Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks
Time frame: Baseline to end of 14 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing | -1.35 mmol/L | Standard Error 0.37 |
| Cotadutide 300 µg | Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing | -1.57 mmol/L | Standard Error 0.35 |
| Cotadutide 600 µg | Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing | -1.69 mmol/L | Standard Error 0.4 |
| Placebo ug | Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing | -0.54 mmol/L | Standard Error 0.37 |
Secondary
Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing
Absolute change in fasting glucose of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks
Time frame: Baseline to end of 26 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing | -1.78 mmol/L | Standard Error 0.36 |
| Cotadutide 300 µg | Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing | -1.76 mmol/L | Standard Error 0.37 |
| Cotadutide 600 µg | Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing | -1.57 mmol/L | Standard Error 0.39 |
| Placebo ug | Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing | -0.72 mmol/L | Standard Error 0.37 |
Secondary
Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing
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
Time frame: Baseline to 14 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing | -13.87 Percent Change | Standard Error 3.35 |
| Cotadutide 300 µg | Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing | -15.79 Percent Change | Standard Error 3.55 |
| Cotadutide 600 µg | Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing | -13.90 Percent Change | Standard Error 3.52 |
| Placebo ug | Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing | -4.09 Percent Change | Standard Error 3.27 |
Secondary
Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing
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
Time frame: Baseline to 26 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing | -18.06 Percent change | Standard Error 3.33 |
| Cotadutide 300 µg | Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing | -15.38 Percent change | Standard Error 3.76 |
| Cotadutide 600 µg | Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing | -11.91 Percent change | Standard Error 3.51 |
| Placebo ug | Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing | -3.00 Percent change | Standard Error 3.17 |
Secondary
Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing
Percentage change in body weight of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing
Time frame: Baseline to end of 26 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing | -2.60 Percentage change | Standard Error 0.89 |
| Cotadutide 300 µg | Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing | -5.45 Percentage change | Standard Error 0.92 |
| Cotadutide 600 µg | Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing | -7.35 Percentage change | Standard Error 0.99 |
| Placebo ug | Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing | -2.23 Percentage change | Standard Error 0.9 |
Secondary
Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks
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.
Time frame: Baseline to end of 26 weeks of dosing
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Cotadutide 100 ug | Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks | -17.85 Percentage change |
| Cotadutide 300 µg | Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks | -38.68 Percentage change |
| Cotadutide 600 µg | Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks | -57.87 Percentage change |
| Placebo ug | Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks | 11.79 Percentage change |
Secondary
Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing
Percentage change in body weight of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing.
Time frame: Baseline to end of 14 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | -2.84 Percentage change | Standard Error 0.65 |
| Cotadutide 300 µg | Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | -4.15 Percentage change | Standard Error 0.68 |
| Cotadutide 600 µg | Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | -5.40 Percentage change | Standard Error 0.73 |
| Placebo ug | Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing | -1.61 Percentage change | Standard Error 0.66 |
Secondary
Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of Dosing
Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from baseline to end of 14 weeks of dosing
Time frame: Baseline to end of 14 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of Dosing | -0.76 Percent change | Standard Error 0.12 |
| Cotadutide 300 µg | Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of Dosing | -0.82 Percent change | Standard Error 0.12 |
| Cotadutide 600 µg | Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of Dosing | -0.65 Percent change | Standard Error 0.12 |
| Placebo ug | Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of Dosing | -0.08 Percent change | Standard Error 0.12 |
Secondary
Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of Dosing
Percentage change in HbA1c of cotadutide at different dose levels compared to placebo from baseline to end of 26 weeks of dosing
Time frame: Baseline to end of 26 weeks of dosing
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cotadutide 100 ug | Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of Dosing | -0.92 Percent change | Standard Error 0.11 |
| Cotadutide 300 µg | Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of Dosing | -0.92 Percent change | Standard Error 0.11 |
| Cotadutide 600 µg | Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of Dosing | -0.89 Percent change | Standard Error 0.11 |
| Placebo ug | Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of Dosing | -0.25 Percent change | Standard Error 0.11 |