NCT01538329: PREMANDYSK

Amantadine and L-DOPA-induced Dyskinesia in Early Parkinson's Disease

Completed Phase 2 Last updated 6 April 2026

What this trial tests

Phase 2 trial testing Amantadine in Parkinson Disease in 210 participants. Completed in 26 February 2019.

Timeline

4 March 2012

Primary endpoint
20 February 2018

26 February 2019

Quick facts

Lead sponsor	University Hospital, Toulouse
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	210
Start date	4 March 2012
Primary completion	20 February 2018
Estimated completion	26 February 2019
Sites	18 locations across France

Drugs / interventions tested

• Amantadine (AMANTADINE) — full drug profile →
• placebo

Conditions studied

• Parkinson Disease — all drugs for Parkinson Disease →

Sponsor

University Hospital, Toulouse

Who can join

35 and older, any sex, with Parkinson Disease. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Traditionally amantadine is used at the beginning of Parkinson Disease (PD) treatment in the early stages of the disease, as a modest antiparkinsonian symptomatic treatment. This treatment is usually maintained for no more than the first few months of management, before resorting to drugs deemed more effective as dopamine agonists and lévo-DOPA (L-DOPA). A more modern use of the drug is at a more advanced stage of PD when dyskinesia are already established and become disabling for the patients. There is no data between these two extremes of life stages of Parkinsonism. However, the mechanisms of action of amantadine and the pathophysiology of the motor complications induced by L-DOPA, in particular dyskinesia suggest that the early and prolonged use of amantadine in the early years of management, before L-DOPA-induced dyskinesia have already emerged, should have a positive impact on long-term occurrence and fate of these symptoms, possibly through a glutamatergic mechanism of brain plasticity-of the "disease modification" type.

Publications & conference data

4 peer-reviewed publications reference this trial (live from Europe PMC):

1. Motor Complications of Dopaminergic Medications in Parkinson's Disease.
   Freitas ME, Hess CW, Fox SH. · · 2017 · cited 83× · PMID 28511255 · DOI 10.1055/s-0037-1602423
2. Receptor Ligands as Helping Hands to L-DOPA in the Treatment of Parkinson's Disease.
   Del Bello F, Giannella M, Giorgioni G, Piergentili A, et al · · 2019 · cited 23× · PMID 30970612 · DOI 10.3390/biom9040142
3. Amantadine and the Risk of Dyskinesia in Patients with Early Parkinson's Disease: An Open-Label, Pragmatic Trial.
   Kim A, Kim YE, Yun JY, Kim HJ, et al · · 2018 · cited 12× · PMID 29860788 · DOI 10.14802/jmd.18005
4. Effect on Dyskinesia of the Early Combination of Amantadine to Levodopa-Therapy in Parkinson's Disease: A Randomized, Placebo-Controlled Study (PREMANDYSK).
   Rascol O, Ory-Magne F, Meissner WG, Maltête D, et al · · 2026 · PMID 41316871 · DOI 10.1002/mds.70120