Clinical trial NCT04515849: A Study of Cotadutide in Participants Who Have Chronic Kidney Disease With Type 2 Diabetes Mellitus
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 2 Diabetes Mellitus
Chronic Kidney Diseases
Keywords: MEDI0382
T2DM
Cotadutide
Diabetic Kidney Disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2020-08-17
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The Primary Endpoint Was Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks
timeFrame: Baseline to the end of 14 weeks of dosing
Secondary outcomes:
measure: Percentage Change in UACR of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks
timeFrame: Baseline to end of 26 weeks of dosing
measure: Percent Change in Body Weight of Cotatudide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing
timeFrame: Baseline to end of 14 weeks of dosing
measure: Percentage Change in Body Weight of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing
timeFrame: Baseline to end of 26 weeks of dosing
measure: Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 14 of Dosing
timeFrame: Baseline to end of 14 weeks of dosing
measure: Percent Change in HbA1c of Cotadutide at Different Dose Levels Versus Placebo From Baseline to the End of 26 of Dosing
timeFrame: Baseline to end of 26 weeks of dosing
measure: Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 14 Weeks of Dosing
timeFrame: Baseline to end of 14 weeks of dosing
measure: Change in Fasting Glucose of Cotadutide at Different Dose Levels From Baseline Versus Placebo After 26 Weeks of Dosing
timeFrame: Baseline to end of 26 weeks of dosing
measure: Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 14 Weeks of Dosing
timeFrame: Baseline to end of 14 weeks of dosing
measure: Change in 10-day Average Glucose Levels of Cotadutide at Different Dose Levels Versus Placebo From Baseline to End of 26 Weeks of Dosing
timeFrame: Baseline to end of 26 weeks of dosing
measure: Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 14 Weeks of Dosing
timeFrame: Baseline to 14 weeks of dosing
measure: Change in Percentage Time Spent in Hyperglycaemia Over 10 Days of Cotadutide at Different Dose Levels Compared to Placebo After 26 Weeks of Dosing
timeFrame: Baseline to 26 weeks of dosing
Other outcomes:
Locations:
city: Box Hill
country: Australia
facility: Research Site
city: Elizabeth Vale
country: Australia
facility: Research Site
city: Fitzroy
country: Australia
facility: Research Site
city: Heidelberg
country: Australia
facility: Research Site
city: Melbourne
country: Australia
facility: Research Site
city: Merewether
country: Australia
facility: Research Site
city: Oaklands Park
country: Australia
facility: Research Site
city: Wollongong
country: Australia
facility: Research Site
city: Woolloongabba
country: Australia
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Barrie
country: Canada
facility: Research Site
state: Ontario
city: Brampton
country: Canada
facility: Research Site
state: Ontario
city: Concord
country: Canada
facility: Research Site
state: Ontario
city: Etobicoke
country: Canada
facility: Research Site
state: Ontario
city: Oakville
country: Canada
facility: Research Site
state: Ontario
city: Oshawa
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Waterloo
country: Canada
facility: Research Site
state: Ontario
city: Laval
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Dusseldorf
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Kassel
country: Germany
facility: Research Site
city: Ludwigshafen
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Mainz
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Münster
country: Germany
facility: Research Site
city: Riesa
country: Germany
facility: Research Site
city: Sankt Ingbert
country: Germany
facility: Research Site
city: Arakawa-ku
country: Japan
facility: Research Site
city: Chitose-shi
country: Japan
facility: Research Site
city: Fujisawa-shi
country: Japan
facility: Research Site
city: Kamakura-shi
country: Japan
facility: Research Site
city: Obihiro-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Shinjyuku-ku
country: Japan
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Grafton
country: New Zealand
facility: Research Site
city: Havelock North
country: New Zealand
facility: Research Site
city: New Plymouth
country: New Zealand
facility: Research Site
city: Tauranga
country: New Zealand
facility: Research Site
city: Wellington
country: New Zealand
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Grodzisk Mazowiecki
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Skierniewice
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wierzchosławice
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
city: L'Hospitalet de Llobregat
country: Spain
facility: Research Site
city: La Coruna
country: Spain
facility: Research Site
city: Lérida
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Majadahonda
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Palma de Mallorca
country: Spain
facility: Research Site
city: Palma
country: Spain
facility: Research Site
city: Pozuelo de Alarcón
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Vitoria
country: Spain
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: Selvarajah V, Robertson D, Hansen L, Jermutus L, Smith K, Coggi A, Sanchez J, Chang YT, Yu H, Parkinson J, Khan A, Chung HS, Hess S, Dumas R, Duck T, Jolly S, Elliott TG, Baker J, Lecube A, Derwahl KM, Scott R, Morales C, Peters C, Goldenberg R, Parker VER, Heerspink HJL; study investigators. A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease. Kidney Int. 2024 Dec;106(6):1170-1180. doi: 10.1016/j.kint.2024.08.023. Epub 2024 Aug 31.