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

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Levodopa dispersible; Drug: Levodopa

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • SMG-SNU Boramae Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 31 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
relationship between delayed ON and response to investigational drugs and the Helicobactor pylori serology and index for atrophic gastritis	whether delayed ON and treatment response are affected by H.pylori status	at baseline and after 4 weeks of each treatment arm

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Samsung Medical Center; SMG-SNU Boramae Medical Center
• Investigators: Principal Investigator: Jee-Young Lee, MD, PhD, SMG-SNU Boramae Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (Estimate): May 12, 2016

Study Record Updates

• Last Update Posted (Actual): May 7, 2021
• Last Update Submitted That Met QC Criteria: May 4, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa; Benserazide; Benserazide, levodopa drug combination
• Other Study ID Numbers: 16-2015-52

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No