Concert Pharmaceuticals, Inc. today announced data from a Phase 1 clinical trial of CTP-499, a novel agent for the potential treatment of diabetic nephropathy. The results demonstrated that a controlled-release formulation of CTP-499 was well-tolerated at single doses up to and including 1800 mg. The company presented these findings during a poster session at the American Society of Nephrology's Kidney Week Meeting in Philadelphia, Pennsylvania. Concert expects to initiate a Phase 2 clinical trial of CTP-499 in patients with diabetic nephropathy during the first half of 2012.
“We believe that the properties of CTP-499 and its metabolites may result in favorable biologic activity as an anti-inflammatory, anti-oxidant and anti-fibrotic agent in chronic kidney disease”
"We believe that the properties of CTP-499 and its metabolites may result in favorable biologic activity as an anti-inflammatory, anti-oxidant and anti-fibrotic agent in chronic kidney disease," said James Shipley, M.D., Chief Medical Officer of Concert Pharmaceuticals. "We look forward to advancing CTP-499 into a proof-of-concept study in patients with type 2 diabetes and renal impairment."
The Phase 1 clinical trial was a randomized, double-blind, placebo-controlled, single ascending-dose study in 38 healthy volunteers. The primary objective of the study was to evaluate the safety, tolerability and pharmacokinetics of a controlled-release formulation of CTP-499 given as a single dose to four successive cohorts of 8 healthy subjects each (600 mg, 1200 mg, 1800 mg, and 2400 mg). For comparison purposes, six additional healthy subjects received a single dose of 400 mg of CTP-499 as an immediate release formulation. All adverse events were mild in nature and no serious adverse events were reported.
Previously, Concert conducted a Phase 1 study in 16 healthy volunteers to evaluate various formulations of CTP-499. The study supported the selection of a controlled-release formulation for the single ascending dose study and subsequent clinical development. CTP-499 will be dosed 600 mg twice daily in the Phase 2 proof-of-concept study.
The clinical studies were undertaken following promising results in the preclinical evaluation of CTP-499. In a series of in vitro experiments, CTP-499 exhibited anti-fibrotic, anti-inflammatory and anti-oxidative properties associated with inter-related pathological mechanisms that may underlie chronic kidney disease. In the streptozotocin (STZ) in vivo preclinical model of diabetic nephropathy, treatment with CTP-499 was protective against model-induced kidney pathologies and it reduced the expression of inflammatory cytokines and MMP-2. These results suggest CTP-499 can impact these key parameters of renal dysfunction, and support the potential of CTP-499 to treat diabetic nephropathy.
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