Tolerability and Pharmacokinetics of Lobeglitazone (CKD-501), a Peroxisome Proliferator-Activated Receptor-γ Agonist: A Single- and Multiple-Dose, Double-Blind, Randomized Control Study in Healthy Male Korean Subjects

Jung Won Kim, Jung Ryul Kim, So Jeong Yi, Kwang Hee Shin, Hyun Suk Shin, Seo Hyun Yoon, Joo Youn Cho, Dal Hyun Kim, Sang Goo Shin, In Jin Jang, Kyung Sang Yu

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Background: Lobeglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist with partial PPAR-α affinity, was developed to treat type 2 diabetes mellitus. Objective: This study's aim was to evaluate the tolerability and pharmacokinetic (PK) properties of lobeglitazone to satisfy regulatory requirements for marketing approval in Korea. Methods: A block-randomized, double-blind, placebo-controlled, single- and multiple-dose study was conducted in healthy subjects. In the pilot study, 4 subjects were administered 0.5 mg, including 1 receiving a placebo. Then, the single-dose study was conducted with 1, 2, 4, and 8 mg doses (8 subjects in each group, including 2 receiving placebos), followed by the multiple-dose study with 1, 2, and 4 mg doses (once daily for 7 days; 8 subjects in each group, including 2 receiving placebos). Serial samples of blood and urine were collected and drug concentrations were determined by high turbulence liquid chromatography-LC/MS/MS. Tolerability assessments were performed throughout the study. Adverse events (AEs) were determined from general health-related questions and self-reports. Results: Thirty-six (mean [SD]; age, 23.6 [2.7] years; weight, 70.0 [6.9] kg) and 25 Korean male subjects (age, 23.5 [3.1] years; weight 69.4 [9.4] kg) were enrolled in the single- and multiple-dose studies, respectively. The data from subjects administered lobeglitazone who completed the study (27, single; 18, multiple) was included in the PK analyses. In the single-dose study, the AUC and C max of lobeglitazone increased with the dose. After repeated dosing for 7 days, the accumulation ratio ranged from 1.1 to 1.4. A total of 25 AEs were reported by 11 (30.6%) and 8 subjects (33.3%) in the single- and multiple-dose studies, respectively. All AEs were mild in intensity and not serious. Conclusions: Lobeglitazone was well tolerated in this small, selected group of healthy male Korean volunteers. The AUC and C max of lobeglitazone increased in a dose-proportional manner from 1 to 4 mg.

Original languageEnglish
Pages (from-to)1819-1830
Number of pages12
JournalClinical Therapeutics
Issue number11
StatePublished - 1 Nov 2011


  • Lobeglitazone
  • PPAR-γ agonist
  • Pharmacokinetics
  • Tolerability

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