Clinical Trial: Safety and Tolerability of Perampanel in Cervical Dystonia

Study Status: Completed
Recruit Status: Unknown status
Study Type: Interventional

Official Title: An Open-label Phase 2a Study to Evaluate the Safety and Tolerability of Perampanel (E2007) in Subjects With Cervical Dystonia (SAFE-Per CD)

Brief Summary: Cervical dystonia (CD) is the most common focal dystonia. Currently there are no effective oral medications for the treatment of CD. While botulinum toxin injections improve symptoms, they require repeated injections by a trained physician and some patients stop responding to injections or never respond at all. Therefore, alternative treatment options for CD are needed. One new agent is a drug that targets glutamate receptors that are thought to be involved dystonia. This drug, perampanel, was originally developed for epilepsy and is licensed for use in the USA and Canada for treating epilepsy. The purpose of this study is to test the effectiveness of perampanel in treating the symptoms of CD.

Detailed Summary:

Idiopathic cervical dystonia (CD) is the most common form of focal dystonia with a prevalence of approximately 60 cases per million population.(Nutt et al.,1988). Current oral medical treatments for CD have variable efficacy and often with marked side effects. Botulinum toxin injections may be more effective than pharmacological therapies, and are currently the best available therapeutic option. However, repeat injections, administered by a physician trained in this area are required every 3-4 months.(Brans et al.,1996) This can often be difficult and costly for patients. Furthermore, there are subgroups of patients who simply do not respond to this treatment and between 5-20% of patients may become secondary non responders due to the development of blocking antibodies to the botulinum toxin.(Mejia et al., 2005) Thus, new therapeutic options are required.

The neural mechanisms underlying idiopathic dystonia are not well known. Classical basal ganglia circuitry models predict underactivity of the output regions of the basal ganglia, the medial globus pallidus and substantia nigra pars reticulata (;Mitchell et al 1990). In subjects with dystonia undergoing DBS, intraoperative recordings have demonstrated underactivity of the medial globus pallidus (Vitek et al, 1999, Lozano et al 1997). One mechanism responsible for these basal ganglia output changes may be overactivity of corticostriatal glutamatergic pathways, as similar neural mechanism are thought to underlie other hyperkinetic movements (Brotchie 2005). The best studied hyperkinetic movement disorder is levodopa-induced dyskinesia in Parkinson's disease in which dystonia, often of the head and neck, may occur. In animal models of levodopa-induced dyskinesia, increased striatal glutamatergic signaling via alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid (AMPA) receptors has been demonstrated (Perier et a
Sponsor: University Health Network, Toronto

Current Primary Outcome: Number of subjects able to remain on study drug for minimum of 4 weeks. [ Time Frame: Measured at week 12. ]

Tolerability will be assessed by counting number of subjects able to remain on drug


Original Primary Outcome: Same as current

Current Secondary Outcome: Adverse events; number of subjects with serious and non-serious adverse events [ Time Frame: Adverse events at study visits weeks 0, 2, 6, 8, 9, 10 and 12 ]

Adverse events will be assessed at each visit by direct questioning patients, measuring weight, vital signs, Hamilton depression scale and laboratory tests and ECG


Original Secondary Outcome: Same as current

Information By: University Health Network, Toronto

Dates:
Date Received: April 23, 2014
Date Started: September 2014
Date Completion: September 2016
Last Updated: May 2, 2014
Last Verified: February 2014