Pharmacokinetics, pharmacodynamics, and tolerability of aleglitazar in patients with type 2 diabetes: results from a randomized, placebo-controlled clinical study.

Abstract

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 alpha/gamma (PPARalpha/gamma) 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 microg) 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 microg. The PPARalpha- and PPARgamma-related effects occurred over similar dose ranges, indicating that aleglitazar is a balanced agonist of the two receptor subtypes.

• Authors: P Sanwald-Ducray, X Liogier D'ardhuy, C Jamois, L Banken
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 88 Issue 2 Pg. 197-203 (Aug 2010) ISSN: 1532-6535 [Electronic] United States
• PMID: 20336066 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoglycemic Agents
• Oxazoles
• Thiophenes
• aleglitazar
• C-Reactive Protein

Topics

• Aged
• Area Under Curve
• C-Reactive Protein (metabolism)
• Diabetes Mellitus, Type 2 (drug therapy)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Half-Life
• Humans
• Hypoglycemic Agents (adverse effects, pharmacokinetics, therapeutic use)
• Male
• Middle Aged
• Oxazoles (adverse effects, pharmacokinetics, therapeutic use)
• Socioeconomic Factors
• Thiophenes (adverse effects, pharmacokinetics, therapeutic use)