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Pharmacokinetics, Pharmacodynamics, and Tolerability of Aleglitazar in Patients With Type 2 Diabetes: Results From a Randomized, Placebo‐Controlled Clinical Study
Author(s) -
SanwaldDucray P,
Liogier D'ardhuy X,
Jamois C,
Banken L
Publication year - 2010
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.259
Subject(s) - tolerability , pharmacodynamics , medicine , pharmacokinetics , placebo , postprandial , pharmacology , adverse effect , dosing , type 2 diabetes , endocrinology , diabetes mellitus , insulin , alternative medicine , pathology
This multicenter, randomized, double‐blind, placebo‐controlled, ascending‐dose study investigated the pharmacokinetics, pharmacodynamic effects, safety, and tolerability of aleglitazar, a novel peroxisome proliferator–activated receptor α/γ (PPARα/γ) dual agonist. After a 3‐week washout period, 71 patients with type 2 diabetes received either a single oral dose of aleglitazar (20, 50, 100, 300, 600, or 900 µg) or placebo, followed by once‐daily dosing for 6 weeks. Few adverse events were reported, with no apparent relationship between the rate of incidence or severity of the adverse events and the dose of aleglitazar administered. Aleglitazar exposure increased in a dose‐proportional manner both after a single dose and at steady state, with no accumulation. Aleglitazar produced dose‐dependent improvements in levels of fasting and postprandial glucose, insulin resistance, and lipid parameters. Dose‐dependent decreases from baseline in creatinine clearance exceeded 10% at doses >300 µg. The PPARα‐ and PPARγ‐related effects occurred over similar dose ranges, indicating that aleglitazar is a balanced agonist of the two receptor subtypes. Clinical Pharmacology & Therapeutics (2010) 88 2, 197–203. doi: 10.1038/clpt.2009.259