{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T21:46:56Z","timestamp":1784238416622,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cotadutide is a dual glucagon\u2010like peptide\u20101\/glucagon receptor agonist. The objective of the analysis was to develop a pharmacokinetic\u2010pharmacodynamic (PK\/PD) model to describe the relationship between cotadutide exposure and response on urine albumin\u2010to\u2010creatinine ratio (UACR), urinary albumin (UALB), and body weight in participants with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) using data from a Phase2b study (NCT04515849).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A total of 247 participants with CKD and T2DM were randomized and titrated to either 100, 300 or 600\u2009\u03bcg cotadutide, 1\u2009mg semaglutide or placebo. UACR was measured biweekly from either morning void (Weeks 14 and 26) or spot urine (other visits). The analysis was implemented using a longitudinal non\u2010linear mixed\u2010effect model. The potential impact of covariates on efficacy in participants was quantified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PK\/PD models were developed, and a significant relationship was identified between cotadutide exposure and PD biomarkers of UACR, UALB and body weight. The models described the data adequately; greater changes in PD responses were observed with higher cotadutide doses. Baseline mean blood pressure and baseline UALB were found to affect the reductions in UACR and UALB, respectively. Model\u2010predicted relative change from placebo in UACR, UALB and body weight after 26\u2009weeks of 600\u2009\u03bcg cotadutide treatment were \u221245.6% (\u221252.4%, \u221238.7%), \u221247.2% (\u221256.0%, \u221239.9%) and \u22125.3% (\u22127.6%, \u22124.1%), respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This modelling assessment was successfully applied for cotadutide to understand the relationship between cotadutide dosing regimen and the response in UACR, UALB and body weight. These models have general application in analysing and interpreting data from CKD\/diabetic kidney disease (DKD) studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70093","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T07:10:13Z","timestamp":1746774613000},"page":"2672-2683","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetic\u2010pharmacodynamic (PK\/PD) modelling of cotadutide effect in patients with chronic kidney disease and type 2 diabetes mellitus"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2278-4478","authenticated-orcid":false,"given":"Hongtao","family":"Yu","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology &amp; Safety Sciences, R&amp;D, AstraZeneca  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Parker","sequence":"additional","affiliation":[{"name":"Early Clinical Development, R&amp;D, AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viknesh","family":"Selvarajah","sequence":"additional","affiliation":[{"name":"Early Clinical Development, R&amp;D, AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Hansen","sequence":"additional","affiliation":[{"name":"Early Clinical Development, R&amp;D, AstraZeneca  Gaithersburg UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Robertson","sequence":"additional","affiliation":[{"name":"Early Clinical Development, R&amp;D, AstraZeneca  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt","family":"Hamr\u00e9n","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology &amp; 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