Phase 2 · Semaglutide

NCT04515849 trial results

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

The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks (Percentage change), Baseline to the end of 14 weeks of dosing. Cotadutide 100 ug: -10.96; Cotadutide 300 µg: -40.47; Cotadutide 600 µg: -44.60; Placebo ug: 4.60.

Participants
248
Status
completed
Completed
2022-03-08
Sponsor
AstraZeneca

As posted on ClinicalTrials.gov (NCT04515849), updated at source Jan 17, 2025. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What NCT04515849 measured first

The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 WeeksPercentage change · Baseline to the end of 14 weeks of dosing · geometric least squares mean
Cotadutide 100 ugn=49Cotadutide 300 µgn=43Cotadutide 600 µgn=37Placebo ugn=43
-10.96(-29.60 to 12.61)-40.47(-53.00 to -24.60)-44.60(-56.21 to -29.91)4.60(-18.02 to 33.46)
Side effects by arm

Side effects in NCT04515849

Percent of participants affected, Screening throughout the treatment period and including the follow-up period (28 days post last dose), an average of 37 weeks.. The most common events the registry lists.

EventCotadutide 100 ugCotadutide 300 ugCotadutide 600 ugPlacebo ugSemaglutide 1 mg
Any serious event9.6%10.2%9.8%9.8%11.1%
Hypoglycaemia25%32.7%25.5%25.5%8.9%
Nausea11.5%14.3%27.5%9.8%26.7%
Decreased appetite0%6.1%9.8%2%17.8%
Diarrhoea9.6%14.3%11.8%7.8%15.6%
Vomiting3.8%6.1%13.7%3.9%15.6%
Constipation13.5%4.1%9.8%3.9%6.7%
Hypotension0%2%5.9%0%11.1%
Dizziness1.9%8.2%3.9%2%2.2%
Dyspepsia1.9%8.2%0%0%0%
Back pain3.8%4.1%5.9%7.8%4.4%
Hyperkalaemia1.9%2%2%3.9%6.7%
Gastrooesophageal reflux disease1.9%4.1%5.9%0%6.7%
Nasopharyngitis3.8%0%0%5.9%6.7%
Urinary tract infection0%6.1%3.9%2%4.4%
Arthralgia0%2%3.9%5.9%2.2%
Pain in extremity1.9%0%0%5.9%2.2%
Headache1.9%2%5.9%2%4.4%
Cough0%2%3.9%5.9%0%
Pyrexia0%0%0%5.9%2.2%
Fatigue5.8%0%2%2%2.2%
Glomerular filtration rate decreased0%2%0%0%4.4%
Myalgia0%2%0%2%4.4%
Asthenia0%4.1%0%0%4.4%
Covid-193.8%2%2%3.9%4.4%
Contusion0%4.1%0%2%0%
Secondary outcomes

What else it measured

Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 WeeksPercentage change · Baseline to end of 26 weeks of dosing · geometric least squares mean
Cotadutide 100 ugn=49Cotadutide 300 µgn=46Cotadutide 600 µgn=48Placebo ugn=49
-17.85(-45.47 to 23.78)-38.68(-59.61 to -6.88)-57.87(-73.33 to -33.45)11.79(-27.85 to 73.22)
Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of DosingPercentage change · Baseline to end of 14 weeks of dosing · least squares mean
Cotadutide 100 ugn=37Cotadutide 300 µgn=32Cotadutide 600 µgn=27Placebo ugn=35
-2.84(0.65)-4.15(0.68)-5.40(0.73)-1.61(0.66)
Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of DosingPercentage change · Baseline to end of 26 weeks of dosing · least squares mean
Cotadutide 100 ugn=37Cotadutide 300 µgn=33Cotadutide 600 µgn=27Placebo ugn=35
-2.60(0.89)-5.45(0.92)-7.35(0.99)-2.23(0.90)
Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of DosingPercent change · Baseline to end of 14 weeks of dosing · least squares mean
Cotadutide 100 µgn=49Cotadutide 300 µgn=45Cotadutide 600 µgn=48Placebo ugn=39
-0.76(0.12)-0.82(0.12)-0.65(0.12)-0.08(0.12)
Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of DosingPercent change · Baseline to end of 26 weeks of dosing · least squares mean
Cotadutide 100 µgn=49Cotadutide 300 µgn=46Cotadutide 600 µgn=48Placebo ugn=39
-0.92(0.11)-0.92(0.11)-0.89(0.11)-0.25(0.11)
Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosingmmol/L · Baseline to end of 14 weeks of dosing · least squares mean
Cotadutide 100 ugn=42Cotadutide 300 µgn=45Cotadutide 600 µgn=48Placebo ugn=49
-1.35(0.37)-1.57(0.35)-1.69(0.40)-0.54(0.37)
Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosingmmol/L · Baseline to end of 26 weeks of dosing · least squares mean
Cotadutide 100 ugn=45Cotadutide 300 µgn=43Cotadutide 600 µgn=39Placebo ugn=45
-1.78(0.36)-1.76(0.37)-1.57(0.39)-0.72(0.37)
Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosingmmol/L · Baseline to end of 14 weeks of dosing · least squares mean
Cotadutide 100 ugn=30Cotadutide 300 µgn=25Cotadutide 600 µgn=26Placebo ugn=30
-1.556(0.320)-1.478(0.337)-1.269(0.334)-0.440(0.311)
Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosingmmol/L · Baseline to end of 26 weeks of dosing · least squares mean
Cotadutide 100 ugn=25Cotadutide 300 µgn=18Cotadutide 600 µgn=22Placebo ugn=30
-1.735(0.307)-1.446(0.334)-1.118(0.321)-0.273(0.290)
Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of DosingPercent Change · Baseline to 14 weeks of dosing · least squares mean
Cotadutide 100 ugn=30Cotadutide 300 µgn=25Cotadutide 600 µgn=26Placebo ugn=30
-13.87(3.35)-15.79(3.55)-13.90(3.52)-4.09(3.27)
Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of DosingPercent change · Baseline to 26 weeks of dosing · least squares mean
Cotadutide 100 ugn=25Cotadutide 300 µgn=18Cotadutide 600 µgn=22Placebo ugn=27
-18.06(3.33)-15.38(3.76)-11.91(3.51)-3.00(3.17)
The trial

How NCT04515849 was run

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.

  • Cotadutide 100 micrograms: Cotadutide 100 micrograms administered subcutaneously
  • Cotadutide 300 micrograms: Cotadutide 300 micrograms administered subcutaneously
  • Cotadutide 600 micrograms: Cotadutide 600 micrograms administered subcutaneously
  • Placebo: Placebo administered subcutaneously
  • Semaglutide: Semaglutide 1.0 miligrams administered subcutaneously
Who could join the trial

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,...

Published papers

Papers from NCT04515849

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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