Study to Evaluate the Efficacy, Safety, and Tolerability of PXT002331 (Foliglurax) in Reducing Levodopa-Induced Dyskinesia and Wearing OFF in Subjects With Parkinson's Disease Experiencing Motor Complications of Levodopa Therapy (ATTUNED)

Study Overview
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Brief Summary
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This is a Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-arm Phase IIa proof of concept in subjects with PD treated with a stable dose of levodopa who are experiencing Motor Complications of Levodopa Therapy

Official Title
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A Multi-center, Double-blind, Randomized, Placebo-controlled, Parallel-arm Phase IIa Trial to Evaluate the Efficacy, Safety, and Tolerability of 8-week Oral Treatment With PXT002331 (Foliglurax) in Reducing Levodopa-Induced Dyskinesia and Wearing OFF in Subjects With Parkinson's Disease Experiencing Motor Complications of Levodopa Therapy (ATTUNED)

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Placebo oral capsule
* Drug: PXT002331 - 20mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 35 and 85 years of age, inclusive, at the time of signing informed consent Diagnosed after the age of 30 years with idiopathic PD A documented medical history of idiopathic PD for at least 3 years Disease severity of 2 to 4 on the modified Hoehn and Yahr scale when in the OFF state Been treated with a stable regimen of levodopa-containing therapy Subjects must be receiving at least 3 doses per day of levodopa-containing therapy, and must be on a stable dose for at least 2 weeks for immediate-release levodopa or at least 6 weeks for prolonged-release levodopa preparations prior to the first screening visit Experienced LID over a period of at least 3 months prior to randomization If needed, in the opinion of the investigator, subjects must have a caregiver Female subjects will be women of non-childbearing potential Exclusion Criteria: Patient is currently participating in or has participated in another study in the last 3 months Subjects with atypical, secondary, or drug-induced Parkinsonism Subjects with a history of dyskinesia that was exclusively diphasic, OFF state, myoclonic, dystonic, or akathetic without peak-dose dyskinesia Subjects with a MoCA score of <25 Subjects who have, or who had a history of, any clinically significant hepatic or gallbladder disorder, as determined by the investigator Subjects who have dementia, currently active psychosis, or hallucinations. Suicide attempt within 1 year prior to the first screening visit, or severe suicidal ideation within 6 months prior to the first screening visit Subject has a current diagnosis of epilepsy, Any known contraindication to the use of levodopa, including a history of malignant melanoma or a history of narrow-angle glaucoma Carcinoma or successfully treated squamous cell carcinoma of the skin and no sing of disease recurrence for at least 5 years Subjects who have had a clinically significant illness within 4 weeks before the first dose, as determined by the investigator Subjects with scheduled surgeries/hospitalizations during the study period Any advanced, severe, or unstable disease (other than PD) that may interfere with the primary and secondary study outcome evaluations Subjects who have undergone prior neurosurgical operation for PD, Subjects currently taking (or expected to be administered during the course of the study) any of the prohibited medications (amantadine, safinamide, dopamine-antagonists).

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PLACEBO<br> | Drug: Placebo oral capsule<br>* BID<br>|
| Experimental: PXT002331 - 20mg<br> | Drug: PXT002331 - 20mg<br>* Oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Unified Dyskinesia Rating Scale (UDysRS) total score in subjects with PD experiencing levodopa-induced dyskinesia. |  | 26 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's Disease, mGlu4 PAM, Levodopa-Induced Dyskinesia (LID), Foliglurax