Mavoglurant (AFQ056) in combination with increased levodopa dosages in Parkinson's disease patients.

Abstract

Long-term use of levodopa (L-dopa) in patients with Parkinson's disease is associated with development of dyskinesia. This study explored whether Parkinson's disease patients with L-dopa-induced dyskinesia experience improved OFF-time from higher L-dopa doses without worsening of dyskinesias when receiving adjunctive mavoglurant. Patients with moderate-to-severe L-dopa-induced dyskinesia were randomized to receive mavoglurant or placebo. Mavoglurant (AFQ056) was up-titrated over two weeks from 25 mg twice daily (bid) to 100 mg bid (L-dopa kept stable), followed by three weeks during which the daily L-dopa dosage was increased by up to 300 mg/day. A sample size of 30 was initially planned; however, the study was terminated prematurely due to enrollment challenges. OFF-time showed greater improvements in the mavoglurant group (n = 7) compared with the placebo group (n = 7); difference at week 5 was -2.77 h (90% confidence interval -5.44, -0.09 h; p = 0.09). ON-time without troublesome dyskinesia increased more from baseline to week 5 in the mavoglurant group (4.38 h) versus the placebo group (0.63 h). Clinician-rated measures were conflicting. The Modified Abnormal Involuntary Movement Scale scores showed a slight improvement with mavoglurant compared with placebo, while the Unified Dyskinesia Rating Scale parts III and IV worsened slightly with mavoglurant compared with placebo. Due to the low patient numbers and conflicting clinician-rated outcomes data, our findings are not conclusive. However, our results suggest that mavoglurant combined with higher doses of L-dopa may be effective in treating patients with Parkinson's disease experiencing L-dopa-related motor fluctuations and dyskinesias.

• Authors: Rajeev Kumar, Robert A Hauser, Joseph Mostillo, Nalina Dronamraju, Ana Graf, Martin Merschhemke, Christopher Kenney
• Journal: The International journal of neuroscience (Int J Neurosci) Vol. 126 Issue 1 Pg. 20-4 ( 2016) ISSN: 1563-5279 [Electronic] England
• PMID: 24007304 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Excitatory Amino Acid Antagonists
• Gluk1 kainate receptor
• Indoles
• Receptors, Kainic Acid
• Levodopa
• mavoglurant

Topics

• Adult
• Aged
• Aged, 80 and over
• Antiparkinson Agents (administration & dosage, adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Synergism
• Drug Therapy, Combination
• Early Termination of Clinical Trials
• Excitatory Amino Acid Antagonists (administration & dosage, adverse effects, therapeutic use)
• Female
• Humans
• Indoles (administration & dosage, adverse effects, therapeutic use)
• Levodopa (administration & dosage, therapeutic use)
• Male
• Middle Aged
• Parkinson Disease (drug therapy)
• Receptors, Kainic Acid (antagonists & inhibitors)
• Sample Size
• Severity of Illness Index
• Tremor (chemically induced)