Date: 2012-12-27
Type of information: Results
phase: 2
Announcement: results
Company: Biotie Therapies (Finland)
Product: nepicastat (SYN117)
Action
mechanism: dopamine hydroxylase inhibitor. Nepicastat (SYN117) is an orally administered, potent and selective inhibitor of the enzyme dopamine beta hydroxylase (DBH), the enzyme responsible for the conversion of dopamine into norepinephrine. The compound was licensed from Roche in 2007.
Nepicastat has potential application in the treatment of cocaine dependency. Like many other addictions, cocaine dependency is driven by a dysregulation in the dopamine reward system. Mechanistically, inhibition of DBH by SYN117 increases levels of dopamine (which reduces the craving for cocaine) and reduces the levels of norepinephrine (which decreases the pleasurable responses to cocaine and the potential for stress induced relapse following withdrawal).
Nepicastat has also potential application in the treatment of post traumatic stress disorder (PTSD).
Disease: post-traumatic stress disorder (PTSD)
Therapeutic area: Mental diseases
Country: USA
Trial
details: The Phase 2 study was a randomized, placebo-controlled , double-blind study conducted in 100 combat veterans fulfilling diagnostic criteria for PTSD (NCT00659230). It was conducted at 4 VA Medical Centers in the United States, with Dr. Lori Davis from Tuscaloosa VA Medical Center as the Principal Investigator. The subjects were randomized in a 1:1 ratio to receive either 120 mg/day nepicastat or matching placebo for 6 weeks under double-blind conditions. Thereafter, subjects could continue on open-label study drug for an additional 8 weeks.
Efficacy was evaluated with the Clinician-Administered PTSD Scale (CAPS); the primary efficacy variable was the CAPS hyperarousal subscale (CAPS-D). Safety and tolerability were assessed with standard methods, including adverse event inquiries and laboratory analyses.
Latest
news: * On December 27, 2012, Biotie Therapies has reported top-line data from a Phase 2 study evaluating its dopamine beta hydroxylase inhibitor nepicastat (SYN117) in combat veterans suffering from post-traumatic stress disorder (PTSD). The study was funded by the U.S. Department of Defense and conducted as an Investigator-initiated study in the United States using clinical trial material supplied by Biotie.
Treatment with nepicastat was not effective in relieving PTSD-associated symptoms when compared to placebo. Nepicastat was generally well tolerated."We are disappointed with the results of this trial and will work with the study investigators to analyze and understand the data in more detail before deciding on next steps with nepicastat in PTSD\", said Timo Veromaa, President and CEO of Biotie. \"Independent of these results, we will continue to develop nepicastat in cocaine dependence in partnership with the U.S. National Institute of Drug Abuse (NIDA). We expect the first patients to be enrolled into a Phase 2 study in Q1 2013.\"
