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:
- Safety. CTP-354 was generally well tolerated. There were no serious adverse events and no treatment discontinuations. The most common adverse events were dose-related mild and moderate dizziness and somnolence (drowsiness). No sedation or ataxia was observed at the doses evaluated.
- Pharmacokinetics. Across all doses, plasma half-life was approximately 20 hours at steady state. CTP-354 exposure was generally dose-proportional across daily doses ranging from 2 mg to 12 mg.
- Food Effect. Administration of CTP-354 under both fed and fasted conditions provided similar exposure, indicating that it can be dosed without regard to meals.
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.