AVP-923 for Levodopa-induced Dyskinesia in Parkinson's Disease
Dyskinesia Challenge, 2012
Dextromethorphan regulates glutamate and serotonin, brain chemicals that help control movements. In people with Parkinson's disease (PD), brain chemical alterations, coupled with long-term levodopa treatment, can cause abnormal movements called dyskinesia. Previous studies in PD and in laboratory models showed that dextromethorphan can reduce dyskinesia at doses that are well tolerated. This study will evaluate the safety and efficacy of AVP-923 (a mixture of dextromethorphan and quinidine) in the treatment of levodopa-induced dyskinesia in PD patients.
Approximately 16 PD patients will receive a two-week treatment of AVP-923 and a two-week placebo treatment, separated by a two-week break (total duration of six weeks). Treatments will be administered in a random order unknown to participants and investigators. At the end of each two-week period, patients will receive levodopa infused in the vein over two hours to induce dyskinesia. Patients will be monitored throughout the study for side effects, PD symptoms, neurological function and quality of life.
Relevance to Diagnosis/Treatment of Parkinson's Disease:
If shown efficacious, and if benefits are confirmed in larger follow-on clinical trials, AVP-923 may become available as a treatment option to help control dyskinesia. Currently, amantadine is the most commonly prescribed oral treatment for levodopa-induced dyskinedia. However, not all patients benefit; tolerability can be a problem, especially at higher doses that provide the greatest benefit; and there may be loss of benefit over time.
This small study will help determine whether AVP-923 is effective in improving dyskinesia induced by levodopa in PD patients. If successful, this study will help plan larger clinical trials to assess several doses of AVP-923 in PD patients. If AVP-923 is shown to be safe and efficacious, it could become commercially available for treatment of levodopa-induced dyskinesia.
Patients with Parkinson's disease (PD) are often treated with levodopa to increase the amount of dopamine (a "neurotransmitter" that acts as a chemical signal between nerve cells) in the brain. As the PD advances, some patients can experience levodopa-induced dyskinesia (LID), which manifests as involuntary and abnormal muscle movements. Adjustment of PD medicines and use of amantadine can help with LID but are not always effective and more treatment options are needed. A research paper that is being published in the journal Movement Disorders describes the treatment effects of dextromethorphan (DM) used in combination with quinidine (Q) in 13 patients with PD and LID. DM is a drug that works on certain non-dopamine neurotransmitters, and Q prevents DM from being broken down quickly in the liver, allowing DM to reach effective doses in the brain. Patients were treated for 2 weeks at a time with either DM/Q or a matching placebo ("sugar pill"). Changes in LID severity and other PD examinations and questionnaires were recorded by both clinicians and patients. In general, severity of LID improved in patients receiving DM/Q compared with placebo. When asked about LID symptoms, the majority of patients reported they were "much" or "very much improved" over the 2-week treatment period. DM/Q was generally well tolerated and did not appear to exacerbate the other PD movement problems. This small study was exploratory only; larger studies with more participants and longer treatment duration, are needed to verify and expand upon these findings.
Presentations & Publications
Fox, S.H. (in press). Trial of Dextromethorphan/Quinidine to Treat Levodopa-Induced Dyskinesia in Parkinson's Disease. Movement Disorders.
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Senior Vice President, Research and Development at Avanir Pharmaceuticals, Inc.
Location: Aliso Viejo, California, United States