A Study of Efficacy and Safety of Eltoprazine HCl for Treating Levodopa-induced Dyskinesia in Parkinson's Disease Patients

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability and efficacy of eltoprazine to treat levodopa-induced dyskinesia in patients with Parkinson's disease

Detailed Description
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A double-blind, placebo-controlled, crossover, dose-range finding study in patients with Parkinson's disease and levodopa-induced dyskinesia. The study will examine the effects of three different doses of eltoprazine HCl, compared to placebo, on severity of dyskinesia, parkinsonian symptoms, patient function, safety and tolerability, using Parkinson's disease rating scales, patient diaries and physiological measurement of abnormal movement by means of motion sensors.

Official Title
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Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, 4-way Crossover, Dose-finding Study, of Eltoprazine Safety, Tolerability and Efficacy in the Treatment of Levodopa-induced Dyskinesia in Patients With Parkinson's Disease

Conditions
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Parkinson's Disease, Dyskinesia

Intervention / Treatment
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* Drug: Eltoprazine HCl
* Drug: Eltoprazine HCl
* Drug: Eltoprazine HCl
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: outpatient with idiopathic PD stable dose of anti-parkinsonian medication for at least four weeks before the Screening Visit daily levodopa dose ≥300 mg per day divided into at least three doses treated with levodopa for at least three years prior to study entry moderate to severely disabling levodopa-induced dyskinesia for at least three months prior to study entry dyskinesia for, on average, >25% of the waking day Exclusion Criteria: inability to use the motion sensors or electronic diaries correctly surgical treatment for PD, e.g. Deep Brain Stimulation, within the last six months or planned during the study unstable co-existing psychiatric disease including psychosis, depression or cognitive impairment Mini Mental State Examination score of <24 moderate or severe renal, or severe hepatic, impairment treatment with selective serotonin re-uptake inhibitors (SSRI) or any combined serotonin-norepinephrine re-uptake inhibitors (SNRI), such as tryptizol, citalopram, escitalopram, sertraline, mianserin, mirtazapin, paroxetin, venlafaxine and St John's Wort, within four weeks prior to the Screening Visit treatment with medications with the potential for drug-interactions (MAO-A inhibitors, apomorphine, aripiprazol, carbamazepine, clozapine, phenytoin, tramadol, quetiapine, varfaine, valproic acid). Patients taking amantadine will comprise no more than 25% of the study population current history of a clinically significant and uncontrolled medical condition that may affect the safety of the patient or preclude adequate participation in the study pregnant or breast-feeding received any other investigational medicinal product within 30 days of Screening

Ages Eligible for Study
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Minimum Age: 30 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eltoprazine HCl 2.5 mg<br>Eltoprazine HCl 2.5 mg capsules to be taken orally b.i.d. (ie, 5 mg/day) for 3 weeks | Drug: Eltoprazine HCl<br>* 2.5 mg b.i.d. orally for 3 weeks<br>|
| Experimental: Eltoprazine HCl 5.0 mg<br>Eltoprazine HCl 5.0 mg capsules to be taken orally b.i.d. (ie, 10 mg/day) for 3 weeks | Drug: Eltoprazine HCl<br>* 5.0 mg b.i.d. orally for 3 weeks<br>|
| Experimental: Eltoprazine HCl 7.5 mg<br>Eltoprazine HCl 7.5 mg capsules to be taken orally b.i.d. (ie, 15 mg/day) for 3 weeks | Drug: Eltoprazine HCl<br>* 7.5 mg b.i.d. orally for 3 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo capsules to be taken orally b.i.d. for 3 weeks | Drug: Placebo<br>* b.i.d. orally for 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical impact of dyskinesia measured by total UDysRS (Unified Dyskinesia Rating Scale) score | Clinical impact on dyskinesia measured by total UDysRS (Unified Dyskinesia Rating Scale) score at the end of each Treatment Period on Days 21, 42, 63 and 84 | 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| • PD motor symptoms assessed by MDS-UPDRS, diaries and physiological measurement with motion sensor system | • PD motor symptoms assessed by MDS-UPDRS, diaries and physiological measurement with motion sensor system | 84 days | 
| Dyskinesia severity using physiological motion sensor system | Dyskinesia severity using physiological motion sensor system | 84 days | 
| Patient function using MDS-UPDRS and UDysRS questionnaires quantify dyskinesia and Parkinsonian motor symptoms. | Patient function using MDS-UPDRS and UDysRS questionnaires | 84 days | 
| Safety and tolerability: adverse events, physical and neurological exams, safety laboratory values, vital signs and ECG | Safety and tolerability: adverse events, physical and neurological exams, safety laboratory values, vital signs and ECG | 94 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD, levodopa, dyskinesia, parkinsons disease