Concert Pharmaceuticals, Inc. announced today the presentation of Phase 1 data on CTP-347, a deuterium-modified analog of paroxetine for the treatment of hot flashes. Concert presented the results during a poster session at the American College of Clinical Pharmacology’s 38th Annual Meeting. This presentation highlighted that subjects treated with CTP-347 substantially retained cytochrome P450 2D6 (CYP2D6) enzyme activity. This enzyme is necessary for the metabolism of many common drugs, but is irreversibly inactivated by a metabolite of paroxetine, causing significant drug-drug interactions. Concert believes these findings represent the first reported clinical data demonstrating that deuterium substitution can alter a drug’s metabolism to reduce the potential for drug-drug interactions in humans.
“This proof-of-concept study, combined with our preclinical findings, demonstrates how we can apply deuterium chemistry to a proven drug to suppress formation of an undesirable metabolite, while retaining the drug’s beneficial pharmacologic activity,” said Roger Tung, Ph.D., President and Chief Executive Officer. “These are exciting results and provide one example of how our deuterium chemistry platform can leverage proven drugs to create highly differentiated yet risk-reduced new medicines.”
The Phase 1 clinical trial was a randomized, single-blind, placebo-controlled, ascending single- and multiple-dose study in 94 healthy volunteers. The primary objective of the study was to evaluate the safety, tolerability and pharmacokinetics of CTP-347. In this trial, CTP-347 was well-tolerated at all doses evaluated and there were no clinically significant adverse events reported. The most common adverse events were typical of selective serotonin reuptake inhibitors (SSRIs) including headache, nausea and dizziness. In vitro studies have previously shown that CTP-347, unlike paroxetine, does not exhibit mechanism-based inactivation of CYP2D6 in human liver microsomes. The pharmacokinetics of CTP-347 were consistent with those observed in preclinical studies.