OREANDA-NEWS. Addex Therapeutics (SIX: ADXN) announced today that results from its Phase 2 clinical study of dipraglurant in levodopa-induced dyskinesia associated with Parkinson's disease have been published in the online issue of the peer-reviewed journal Movement Disorders, "A Phase 2A Trial of the Novel mGluR5-Negative Allosteric Modulator Dipraglurant for Levodopa-Induced Dyskinesia in Parkinson's Disease" Mov Disord. 2016 May 23.

Dipraglurant is being developed by Addex for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease. Dipraglurant is a novel, highly potent mGluR5 negative allosteric modulator (NAM) with a pharmacokinetic profile that mimics that of levodopa, making it particularly well suited to treat LID.

"The Phase 2 study suggests that dipraglurant improved dyskinesia in Parkinson's disease patients." commented Sonia Poli, Chief Scientific Officer of Addex. "We believe dipraglurant has a unique profile that is particularly suited for the treatment of PD-LID and we look forward to rapidly advancing dipraglurant into Phase III development"

"Levodopa-induced dyskinesia can be debilitating in its own right and can impact the use of medications to treat Parkinson's motor symptoms," said Jamie Eberling, PhD, MJFF Director of Research Programs. "A therapy, such as dipraglurant, to control this side effect would have a great impact on the lives of many living with this disease."

The publication reports the results of clinical trial ADX48621-201 (NCT01336088). The study was a phase 2A double-blind, placebo-controlled, randomized (2:1), 4-week, parallel-group, multicenter dose-escalation (from 50 mg once daily to 100 mg 3 times daily) clinical trial involving 76 PD subjects with moderate to severe levodopa-induced dyskinesia. Fifty-two patients were exposed to dipraglurant and 24 to placebo.

The primary objective of the study was to evaluate the safety and tolerability of ADX48621 in Parkinson's disease patients following four weeks of dosing. The secondary objectives of the study included the evaluation of the efficacy of ADX48621 compared with placebo in reducing levodopa induced dyskinesia in patients with Parkinson's; the evaluation of the effect of ADX48621 on symptoms of Parkinson's disease and patient ability to function, and the evaluation of the effect of co-administration of ADX48621 on L-dopa efficacy. The study was supported by a grant from The Michael J. Fox Foundation for Parkinson's Research.

The results show that there were no major safety concerns in the trial. Two subjects did not complete the study because of adverse events. Most frequent adverse events included dyskinesia, dizziness, nausea, and fatigue. Dipraglurant significantly reduced peak dose dyskinesia (modified Abnormal Involuntary Movement Scale) on day 1 (50 mg, 20%; P = 0.04) and on day 14 (100 mg, 32%; P =0 .04) and across a 3-hour post-dose period on day 14 (P = 0.04). Most importantly, there was no evidence of worsening of parkinsonism.

The authors conclude that dipraglurant proved to be safe and well tolerated in its first administration to PD patients and that its efficacy in reversing levodopa-induced dyskinesia warrants further investigations in a larger number of patients.