Efficacy of Levodopa/Benserazide Dispersible Tablet on Response Fluctuations in PD Patients With Delayed ON

Study Overview
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Brief Summary
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The purpose of this study is to determine whether levodopa/benserazide dispersible is effective in the adjunctive treatment of Parkinson's disease (PD) patients with delayed ON.

Detailed Description
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Delayed ON is one of the motor complications of advanced PD patients that effect of anti-parkinsonian medication is delayed more than 40 minutes after intake. In the most severe cases, the effect does not appear even until next medication schedule, so called No ON status. It is important to manage delayed ON properly because it can interfere motor functions and quality of life of PD patients. Levodopa/benserazide dispersible can be absorbed rapidly in the intestine, so theoretically it can break the poor response to conventional treatment of PD patients with delayed ON. However, this has not been proven by clinical trials till now.

Official Title
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Efficacy of Levodopa/Benserazide Dispersible Tablet on Response Fluctuations in Parkinson's Disease Patients With Delayed ON: a Multicenter Randomized Open-label Cross-over Trial

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Levodopa dispersible
* Drug: Levodopa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients between 31 and 80 years Parkinson disease (PD) was diagnosed by United Kingdom Parkinson disease brain bank criteria Patients receiving stable Levodopa treatment at least 2 weeks prior to baseline visit Delayed ON was confirmed by a specialized PD diary that records change in motor symptoms 90 minute after the first morning dose. Delayed ON is defined as delay of more than 40 minutes after the first morning dose for resolution of OFF state or experience of no ON state at least 1 per week. Exclusion Criteria: Existence of cognitive decline hard to participate in the clinical trial or K-Minimental Status Exam score 24 or less Any contraindication of blood sampling Subjects with clinically significant psychiatric illness Subjects with a cancer or severe medical illness Lactating, pregnant, or possible pregnant History of malignant melanoma Subjects with narrow-angle glaucoma Subjects with hypersensitivity to levodopa or benserazide Subjects treated with non-selective monoamine oxidase (MAO)-B inhibitors Subjects with peptic ulcer, colitis, or gastrointestinal disease

Ages Eligible for Study
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Minimum Age: 31 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levodopa dispersible<br>Levodopa dispersible 100mg/tablet, PO, 1 tablet in the morning, once daily for 4 weeks (crossover) | Drug: Levodopa dispersible<br>* Levodopa dispersible 100mg/tablet, PO, 1 tablet in the morning, once daily for 4 weeks (crossover)<br>* Other names: Madopar dispersible;|
| Active Comparator: Levodopa<br>Levodopa 100mg/tablet, PO, 1 tablet in the morning, once daily for 4 weeks (crossover) | Drug: Levodopa<br>* Levodopa 100mg/tablet, PO, 1 tablet in the morning, once daily for 4 weeks (crossover)<br>* Other names: Madopar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the time to ON after first morning dose using 3-day PD diary | A specialized 3-day PD diary will be distributed to the patients 3 days prior to each visit. This diary will evaluate the latency of ON after intake of the study medication. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the The Unified Parkinson Disease Rating Scale (UPDRS) | a scale for assessment of parkinsonian symptom severity in PD patients | 4 weeks | 
| Change in the The Unified Dyskinesia Rating Scale (UDyskRS) | a scale for assessment of levodopa-induced dyskinesia in PD patients | 4 weeks | 
| Change in the The Schwab & England Activity of daily living scale (SEADL) | a scale for activity of daily living assessment | 4 weeks | 
| Change in the The Parkinson Disease Questionnaire-39 (PDQ-39) | a scale for health-related quality of life in PD patients | 4 weeks | 
| Change in the Patient global improvement (PGI) | patient-centered assessment of global improvement | 4 weeks | 
| Change in the Clinician global improvement (CGI) | clinician's assessment for global improvement | 4 weeks | 
| Change in the K-Minimental status examination (K-MMSE) | global cognition assessment | 4 weeks | 
| Change in the Total ON time, total OFF time using 3-day PD diary | a severity assessment index for PD patients with motor fluctuation | 4 weeks |