Parkinson Disease (PD)Phase 2AMANT-OFFNCT06817200
The Effect of Amantadine as add-on Therapy for Motor Fluctuations in Advanced Parkinson's Disease: a Randomized Double-blinded Placebo-controlled Trial
A Phase 2 study testing Amantadine (100mg) as add on therapy. in people with Parkinson Disease (PD), run by University Hospital, Toulouse at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Parkinson Disease (PD)
- What is being tested?
- Amantadine (100mg) as add on therapy.
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 132 participants
- Where
- 1 siteFrance
- Study dates
- 1 May 2025to 31 Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site
CHU Toulouse
Toulouse
Margherita FABBRI, MD, 0561776039 ext. +33, fabbri.m@chu-toulouse.fr
Margherita FABBRI, MD
About this study
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.
Read the 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)
- Being tested
- Amantadine (100mg) as add on therapy., Placebo
- Keywords
- Parkinson's disease, clinical trial, Motor fluctuations, Amantadine
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 3 months
Secondary outcomes (8)
The rate of Off-time responders
The change from baseline to end-point (3 months) of the rate of Off-time responders
Measured: 3 months
The change of the mean score of MDS-UPDRS part IV
The change from baseline to end-point (3 months) of The mean score of Movement disorders society - Unified Parkinson's disease rating scale (MDS-UPDRS part IV)
Measured: 3 months
The change of the mean score of UDysRS part 2A
The change from baseline to end-point (3 months) of the mean score of UDysRS part 2A
Measured: 3 months
The change of the mean score of New freezing of gait questionnaire
The change from baseline to end-point (3 months) of the mean score of New freezing of gait questionnaire
Measured: 3 months
The change of the mean score of Fatigue Severity Scale
The change from baseline to end-point (3 months) of the mean score of Fatigue Severity Scale
Measured: 3 months
The change of the mean score of MDS-UPDRS Part I-II-III
The change from baseline to end-point (3 months) of the mean score of Movement disorders society - Unified Parkinson's disease rating scale (MDS-UPDRS Part I-II-III)
Measured: 3 months
The change of the mean score of PDQ-39
The change from baseline to end-point (3 months) of the mean score of Parkinson's Disease Questionnaire (PDQ-39)
Measured: 3 months
The safety of amantadine
The safety of amantadine, expressed as: the percentage of Adverse Events, of severe Adverse Events, of serious Adverse Events and of patients' discontinuation due to Adverse Events, all over the three months of treatment.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2025
- Study start1 May 2025 (estimated)
- Primary completion1 May 2025 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson Disease (PD)Studies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 132 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06817200
- Sponsor's protocol ID
- RC31/23/0372
- Other IDs
- 2023-509728-16-00, 2023
- Acronym
- AMANT-OFF
- Status last verified
- Feb 2025
- First submitted
- 4 Feb 2025
- Last updated
- 10 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Amantadine as add-on Therapy for Motor Fluctuations in Advanced Parkinson's Disease: a Randomized Double-blinded Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT06817200
- Acronym / sponsor ID
- AMANT-OFF / RC31/23/0372
- Conditions
- Parkinson Disease (PD)
- Keywords
- Parkinson's disease, clinical trial, Motor fluctuations, Amantadine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 132 participants (estimated)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 1 May 2025 (estimated)
- Primary completion
- 1 May 2025 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 10 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Amantadine | Experimental | 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. The study treatment will be stopped after a dose decrease of 100 mg / day every 3 days. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Amantadine |
| PlaceboPlacebo 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 |
Primary outcome
the change in motor fluctuation (Off-time)
Time frame: 3 months
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).
8 secondary outcomes
The rate of Off-time responders
Time frame: 3 months
The change of the mean score of MDS-UPDRS part IV
Time frame: 3 months
The change of the mean score of UDysRS part 2A
Time frame: 3 months
The change of the mean score of New freezing of gait questionnaire
Time frame: 3 months
The change of the mean score of Fatigue Severity Scale
Time frame: 3 months
The change of the mean score of MDS-UPDRS Part I-II-III
Time frame: 3 months
The change of the mean score of PDQ-39
Time frame: 3 months
The safety of amantadine
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Amantadine (100mg) as add on therapy. in people with Parkinson Disease (PD), run by University Hospital, Toulouse at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Margherita FABBRI, MD (0561776039 ext. +33, fabbri.m@chu-toulouse.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
the change in motor fluctuation (Off-time) (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2025.