Concert Pharma Initiates Phase 1 Single-Ascending Dose Trial of CTP-692 as an Adjunctive Treatment for Schizophrenia
Concert Pharmaceuticals announced that it has initiated the second Phase 1 clinical trial with CTP-692, a novel deuterium-modified form of D-serine being developed as an adjunctive treatment for schizophrenia. The Phase 1 single-ascending dose trial will evaluate the safety, tolerability, and pharmacokinetic profile of CTP-692 in healthy volunteers.
“For decades all approved schizophrenia drugs have acted predominantly by modulation of dopamine, or dopamine and serotonin receptors. By activating glutamatergic pathways as an NMDA co-agonist, CTP-692 has the potential to be a safe and effective new adjunctive treatment for schizophrenia, and treat positive and negative symptoms and cognitive dysfunction,” stated Roger Tung, Ph.D., President and Chief Executive Officer of Concert Pharmaceuticals, Inc. “We are excited about continuing our Phase 1 program and in the fourth quarter of 2019 are preparing to advance CTP-692 into a Phase 2 trial that is intended to support advancement into pivotal evaluation.”
The initial Phase 1 trial evaluated the safety, tolerability, and pharmacokinetics of a single oral dose of CTP-692 versus D-serine in a crossover study conducted in Australia. In individuals treated with both compounds, CTP-692 was found to have increased plasma exposure compared to D-serine. In addition, CTP-692 was found to be well tolerated in healthy volunteers and no serious adverse events were reported. Under its Investigational New Drug application in the United States, Concert will conduct this second study in the Phase 1 program to assess the safety, tolerability, and pharmacokinetics of single-ascending oral doses of CTP-692 in a double-blind, placebo-controlled trial. The Phase 1 single-ascending dose trial will also evaluate the effect of food on the pharmacokinetics of the compound. In addition, the Phase 1 program will include a double-blind, placebo-controlled, multiple-ascending dose trial assessing CTP-692 dosed orally over seven days. Topline data from the Phase 1 program is expected in the first half of 2019.
The CTP-692 clinical program is supported by Concert’s preclinical studies which have shown the potential of CTP-692 to improve upon the safety profile of D-serine. D-Serine has been shown to cause nephrotoxicity in published preclinical studies. Concert’s preclinical studies have demonstrated that selective deuterium modification resulted in increased exposure of CTP-692 relative to a similar dose of D-serine, and administration of CTP-692 did not cause changes in serum creatinine and blood urea nitrogen at doses where D-serine caused substantial nephrotoxicity as assessed by these kidney function markers. These preclinical results were presented by Concert at the American College of Toxicology 2018 Annual Meeting in November 2018.