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.

KEYWORDS:

• mavoglurant
• AFQ056
• levodopa
• dyskinesia
• Parkinson's disease

Acknowledgements

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. This research is sponsored and conducted by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. We thank Kerrie O’Rourke of iMed Comms for medical editorial assistance with this manuscript.

Declaration of Interest

The authors alone are responsible for the content and writing of this paper.

This research is sponsored and conducted by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Rajeev Kumar's institution has received a grant from Novartis. Rajeev Kumar has received consultancy fees from Novartis, honoraria from Novartis, payment for development of educational presentations, including service on speakers’ bureaux, from Novartis, and travel/accommodations expenses covered or reimbursed by Novartis. Robert A. Hauser's institution has received a grant from Novartis. Robert A. Hauser has received honoraria from Novartis Pharmaceuticals. Joseph Mostillo was employed by Novartis at the time of the study. Nalina Dronamraju is an employee of Novartis. Ana Graf is an employee of Novartis and holds stock options with Novartis. Martin Merschhemke is an employee of Novartis and holds stock options with Novartis. Christopher Kenney is an employee of Novartis.