NCT06817200

The Effect of Amantadine as add-on Therapy for Motor Fluctuations in Advanced Parkinson's Disease: a Randomized Double-blinded Placebo-controlled Trial

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 132 (estimated)
• Sponsor: University Hospital, Toulouse · Academic / Other
• Sex: All
• Age: 30 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

Motor fluctuations are identified as the most challenging symptoms by parkinson disease patients. A recent post-hoc analysis of ADS-5012 trials (new formulation of ER Amantadine), revealed a significant improvement in OFF-time. No randomized clinical trial has ever specifically investigated to date the effect of amantadine IR on motor fluctuations. The main objective of this study is to evaluate the effect of amantadine (300 mg/day) as add-on therapy for the treatment of motor fluctuations (Off-time) in advanced Parkinson's disease patients versus placebo after 3 months of treatment.

Detailed description

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. Up to 50% of parkinson disease patients develop mild motor fluctuations (OFF-time) within 2 years of initiating levodopa therapy, increasing up to 70% of patients after 9 years. Motor fluctuations are identified as the most challenging symptoms by parkinson disease patients and considered as a key clinical unmet need for advanced parkinson disease patients. Amantadine has been approved by the FDA in 1973 for the "treatment of parkinson disease". It has a unique pharmacodynamic profile with both a dopaminergic and an anti-glutamatergic effect, which are related to its anti-parkinsonian and anti-dyskinetic action. In 2017, the FDA approved 2 new Amantadine extended release (ER) formulations for dyskinesia treatment, ADS-5012 and OS-320. In 2021 post-hoc analysis of ADS-5012 trials, revealed a significant improvement in OFF-time (1 h of reduction vs. placebo). These findings led to the FDA granting amantadine ER an additional indication as add-on treatment to levodopa for the management of motor fluctuations. No randomized clinical trial has ever specifically investigated to date the effect of amantadine Immediate Release on motor fluctuations. We hypothesize that the double action of amantadine could allow this drug to be effective in the treatment of motor fluctuations, without increasing dyskinesia. Parkinson disease patient with motor fluctuations will be included and followed up in this study. After 3 to 4 weeks of titration, patients will receive stable dose of amantadine (up to 300 mg/day) or matching placebo during 12 weeks.

Conditions

• Parkinson Disease (PD)

Interventions

Type	Name	Description
DRUG	Amantadine (100mg) as add on therapy.	Amantadine will be administered at the dose of 100 mg t.i.d or b.i.d. (if t.i.d. is not tolerated) over 12 weeks, after a period of 3 weeks of titration.T he study treatment will be stopped after a dose decrease of 100 mg / day every 3 days.
DRUG	Placebo	Placebo tablets will be also administered b.i.d. or t.i.d over 12 weeks after a period of 3 weeks of titration. Placebo tablets will be indistinguishable from amantadine ones.

Timeline

• Start date: 2025-05-01
• Primary completion: 2025-05-01
• Completion: 2027-08-31
• First posted: 2025-02-10
• Last updated: 2025-02-10

Locations

1 site across 1 country: France