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

NCT06817200 | Not Yet Recruiting Phase 2

• 2 other identifiers: RC31/23/03722023-509728-16-00
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Parkinson Disease (PD)

Keywords

Parkinson's disease; clinical trial; Motor fluctuations; Amantadine

Outcome Measures

Primary Outcomes (1)

• the change in motor fluctuation (Off-time)

  The primary outcome of this study is the change from baseline to end-point (3 months) in motor fluctuation (Off-time) as assessed by the Hauser diaries (average of 3 consecutive days).

  3 months

Secondary Outcomes (8)

• The rate of Off-time responders

  3 months

• The change of the mean score of MDS-UPDRS part IV

  3 months

• The change of the mean score of UDysRS part 2A

  3 months

• The change of the mean score of New freezing of gait questionnaire

  3 months

• The change of the mean score of Fatigue Severity Scale

  3 months

Study Arms (2)

Amantadine

EXPERIMENTAL

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. The study treatment will be stopped after a dose decrease of 100 mg / day every 3 days.

Drug: Amantadine (100mg) as add on therapy.

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Amantadine (100mg) as add on therapy. DRUG

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.

Amantadine

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parkinson's disease diagnosis in agreement with the MDS criteria (Postuma et al., 2015) for at least 3 years HY 2-3 in Med ON condition Age: 30-80 years Signs of motor fluctuations for at least 4 weeks before screening, with a mean total awake time in the off state of at least 2 h, including morning akinesia despite anti-parkinsonian drug adjustment (best medical treatment)" Amantadine naïve (all other oral add-on treatments for motor fluctuations are allowed) Concomitant anti-Parkinson drug use should be stable for at least 4 weeks prior to screening Patients affiliated or beneficiary of a social security scheme. Patients who signed the written informed consent form. Patients in capacity to complete Hauser diaries

You may not qualify if:

• Severe or unpredictable periods in the Off-state, or both; Clinically significant and unstable cardiovascular disease, psychiatric illness (including major depression, dementia, impulse control, disorders, and suicide ideation), or any other medical disorder that might have placed the patient at increased risk; Patient with behavioral disorder, ECMP item ≥ 3 Patients previously submitted to advanced treatments: subcutaneous continuous apomorphine infusion, deep brain stimulation and levodopa-carbidopa intestinal gel; Patients with cognitive impairment (Mini Mental Status Examination \< 26) Patients with a diagnosis of atypical parkinsonism (Progressive supranuclear Palsy, Multiple system atrophy, Lewy Body Dementia or Cortico-basal degeneration) Patients having any contraindication to amantadine treatment (see Summary of Product characteristic in the Appendix: known hypersensitivity to drugs of the amantadine class or any of the components, combination with anti-emetic neuroleptics, patient with a history of epilepsy, confusional state, hallucinations or severe psychoneurotic state not controlled by treatment, patient with a history of congestive heart failure or peripheral oedema, patient with a history of skin eczema) A history of neuroleptic malignant syndrome or nontraumatic Rhabdomyolysis; renal failure and renal insufficiency (creatinine \> 150 µmol/L) states of agitation or confusion delirious syndromes or exogenous psychosis in the anamnesis Has received any other investigational drug within 30 days or 5 half-lives (whichever is longer) prior to screening or plans to use an investigational drug (other than the study intervention) during the study Pregnant female subjects or potential childbearing female participant without highly effective contraception

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

CHU Toulouse

Toulouse, France

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Amantadine

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Margherita FABBRI, MD

CONTACT

0561776039; fabbri.m@chu-toulouse.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2025
• First Posted: February 10, 2025
• Study Start: May 1, 2025
• Primary Completion: May 1, 2025
• Study Completion (Estimated): August 31, 2027
• Last Updated: February 10, 2025

Record last verified: 2025-02

Locations

FR (1)