A First-in-Patient, Multicenter, Double-Blind, 2-Arm, Placebo-Controlled, Randomized Safety and Tolerability Study of a Novel Oral Drug Candidate, CTP-499, in Chronic Kidney Disease

Clin Pharmacol Drug Dev. 2016 Jul;5(4):314-25. doi: 10.1002/cpdd.241. Epub 2016 Feb 11.


The prevalence of chronic kidney disease (CKD) related to type 2 diabetes is increasing worldwide. In addition to standard of care, treatment with anti-inflammatory and antifibrotic agents such as CTP-499, a novel oral, multisubtype selective inhibitor of phosphodiesterases, may be important in CKD treatment. A phase 1b randomized, double-blind, placebo-controlled clinical trial of CTP-499 in CKD patients (25 active, 8 placebo) with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m(2) was conducted to assess safety and tolerability. Secondary outcomes included pharmacokinetics and exploratory effects on inflammatory and hematology markers. Patients received 600 mg CTP-499 or matching placebo tablets orally once daily for 2 weeks, then twice daily for 2 additional weeks. CTP-499 was well tolerated with no serious or severe adverse events, or adverse events leading to discontinuation. CTP-499 was rapidly absorbed and produced acceptable interpatient variability. Of the 5 metabolites (M1-M5), M5 was the most abundant in plasma and urine. Exposure to CTP-499 and metabolites was higher in CKD patients than previously reported in healthy volunteers. No statistically significant differences were detected between the CTP-499- and placebo-treated groups for any of the biomarkers tested. This study provides data supporting further evaluation of CTP-499 in CKD patients.

Keywords: CTP-499; chronic kidney disease; deuterium; pharmacokinetics.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Male
  • Middle Aged
  • Pentoxifylline / adverse effects
  • Pentoxifylline / analogs & derivatives*
  • Pentoxifylline / pharmacokinetics
  • Phosphodiesterase Inhibitors / adverse effects*
  • Phosphodiesterase Inhibitors / pharmacokinetics
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology
  • Tablets


  • 1-(5-hydroxyhexyl)-3,7-dimethylxanthine
  • Biomarkers
  • Phosphodiesterase Inhibitors
  • Tablets
  • Pentoxifylline