| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
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