Exposure and response analysis of aleglitazar on cardiovascular risk markers and safety outcomes: An analysis of the AleCardio trial

The AleCardio trial aimed to characterize the efficacy and safety of peroxisome proliferator‐activated receptor‐αγ agonist aleglitazar in patients with type 2 diabetes mellitus and acute coronary syndrome. The trial terminated early because of futility and safety signals. We evaluated whether the safety signals could be attributed to increased exposure to aleglitazar.

[1]  S. Mensing.  Review for "Exposure and response analysis of aleglitazar on cardiovascular risk markers and safety outcomes: An analysis of the AleCardio trial" , 2019 .

[2]  C. Viscoli,et al.  Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. , 2016, The New England journal of medicine.

[3]  P. Neuvonen,et al.  Clopidogrel Markedly Increases Plasma Concentrations of CYP2C8 Substrate Pioglitazone , 2016, Drug Metabolism and Disposition.

[4]  D. Tanné,et al.  Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. , 2016, The New England journal of medicine.

[5]  P. Neuvonen,et al.  Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions , 2016, Pharmacological Reviews.

[6]  P. Mohr.  CHAPTER 26:Aleglitazar: A Case Study , 2014 .

[7]  D. Grobbee,et al.  Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: the AleCardio randomized clinical trial. , 2014, JAMA.

[8]  D. Grobbee,et al.  Evaluation of the dual peroxisome proliferator-activated receptor α/γ agonist aleglitazar to reduce cardiovascular events in patients with acute coronary syndrome and type 2 diabetes mellitus: rationale and design of the AleCardio trial. , 2013, American heart journal.

[9]  D R Mould,et al.  Basic Concepts in Population Modeling, Simulation, and Model-Based Drug Development—Part 2: Introduction to Pharmacokinetic Modeling Methods , 2013, CPT: pharmacometrics & systems pharmacology.

[10]  J. Wilding.  PPAR agonists for the treatment of cardiovascular disease in patients with diabetes , 2012, Diabetes, obesity & metabolism.

[11]  C. Funk,et al.  Metabolism, excretion, and pharmacokinetics of [14c]-radiolabeled aleglitazar: a phase I, nonrandomized, open-label, single-center, single-dose study in healthy male volunteers. , 2012, Clinical therapeutics.

[12]  P. Sanwald-Ducray,et al.  Pharmacokinetics, Pharmacodynamics, and Tolerability of Aleglitazar in Patients With Type 2 Diabetes: Results From a Randomized, Placebo‐Controlled Clinical Study , 2010, Clinical pharmacology and therapeutics.

[13]  S. Mudaliar,et al.  Pioglitazone: side effect and safety profile , 2010, Expert opinion on drug safety.

[14]  B. Kuhn,et al.  Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. , 2009, Bioorganic & medicinal chemistry letters.

[15]  Erland Erdmann,et al.  Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial , 2005, The Lancet.

[16]  Salim Yusuf,et al.  Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study , 2001, The Lancet.

[17]  S. Yusuf,et al.  Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. , 2001, The New England journal of medicine.

[18]  P. R. R. Ecurrent,et al.  EFFECTS OF CLOPIDOGREL IN ADDITION TO ASPIRIN IN PATIENTS WITH ACUTE CORONARY SYNDROMES WITHOUT ST-SEGMENT ELEVATION , 2001 .

[19]  K Thomaseth,et al.  Role of hyperglycemia and insulin resistance in determining sodium retention in non-insulin-dependent diabetes. , 1993, Kidney international.