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

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• 作者：LuAnn Sabounjian ; Philip Graham ; Lijun Wu ; Virginia Braman ; Changfu Cheng ; Julie Liu ; James Shipley ; Joel Neutel and Michael Dao
• 刊名：Clinical Pharmacology in Drug Development
• 出版年：2016
• 出版时间：July/August 2016
• 年：2016
• 卷：5
• 期：4
• 页码：314-325
• 全文大小：701K
• ISSN：2160-7648

文摘

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 m² 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.