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.
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.
Concert Pharmaceuticals, Inc, Lexington, MA, USA.
LuAnn
L
Sabounjian
Concert Pharmaceuticals, Inc, Lexington, MA, USA.
Philip
P
Graham
Concert Pharmaceuticals, Inc, Lexington, MA, USA.
Lijun
L
Wu
Concert Pharmaceuticals, Inc, Lexington, MA, USA.
Virginia
V
Braman
Concert Pharmaceuticals, Inc, Lexington, MA, USA.
Changfu
C
Cheng
Concert Pharmaceuticals, Inc, Lexington, MA, USA.
Julie
J
Liu
Concert Pharmaceuticals, Inc, Lexington, MA, USA.
James
J
Shipley
Orange County Research Center, Tustin, CA, USA.
Joel
J
Neutel
SC Clinical Research, Garden Grove, CA, USA.
Michael
M
Dao
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010726:Phosphodiesterase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D013607:Tablets
C000626018:1-(5-hydroxyhexyl)-3,7-dimethylxanthine; D015415:Biomarkers; D010726:Phosphodiesterase Inhibitors; D013607:Tablets; D010431:Pentoxifylline
CTP-499; chronic kidney disease; deuterium; pharmacokinetics