Published 14 October 2014
Concert Pharmaceuticals has announced Phase 1 data of CTP-354, a novel, potentially first-in-class, non-sedating, once-daily oral treatment for spasticity. In this multiple ascending dose trial, no sedation or ataxia was observed with CTP-354 and the drug was generally well tolerated across all dose cohorts.
The Company will be presenting these findings today during a poster session at the American Neurological Association's Annual Meeting in Baltimore, Maryland. Concert expects to initiate a Phase 2 clinical trial evaluating CTP-354 in patients with spasticity associated with spinal cord injury by the end of 2014.
"We are very pleased to have completed our clinical evaluation of CTP-354 in this Phase 1 trial. We remain on track to advance the program into Phase 2 testing later this year, initially targeting spasticity in patients with spinal cord injury followed by the start of a Phase 2 trial in multiple sclerosis patients in early 2015," stated Roger Tung, Ph.D., President and Chief Executive Officer of Concert Pharmaceuticals.
Dr. Tung added, "CTP-354 was designed to avoid dose-limiting sedation and ataxia, which currently limit the broader use of other GABAA receptor modulators such as benzodiazepines. This trial provides evidence that CTP-354 can achieve high plasma levels without causing those side effects. In addition to being generally well tolerated in our Phase 1 clinical trials, CTP-354 also demonstrated highly favorable pharmacokinetics with low variability, dose-proportional exposure, a long half-life in the body and high levels of GABAA receptor occupancy.
"Taken together, we believe these results support once-daily dosing, which would provide a substantial improvement over the three-times-daily dosing required by current standard-of-care oral spasticity medicines."
The Phase 1 multiple ascending dose clinical trial was a randomized, double-blind, placebo-controlled study in 30 healthy volunteers. The primary objective of the trial was to evaluate the safety, tolerability and pharmacokinetics of 10-day repeat dosing of 2 mg, 6 mg and 12 mg of CTP-354. Clinical highlights include:
The Company previously reported positive results from both a Phase 1 single ascending dose trial and a Phase 1 brain imaging trial as measured by positron emission tomography, or PET imaging.
The long half-life and pharmacokinetic profile observed in the single ascending dose support once-daily dosing of CTP-354. In addition, CTP-354 provided high and sustained brain GABAA receptor occupancy levels in the brain imaging trial in both single and repeat doses.
Based on the results of the Phase 1 trials, Concert intends to advance CTP-354 into Phase 2 clinical evaluation later this year. The Phase 2 program is projected to include two trials: one evaluating spasticity associated with spinal cord injury and one evaluating spasticity associated with multiple sclerosis.