Efficacy and Safety of Entacapone Combined With Madopar in the Treatment of Early Parkinson's Disease: An Observational, Multicenter, Case-Control Study (EM-PD)

June 18, 2025 updated by: Yousheng Xiao

This observational, multicenter, case-control study aims to evaluate the efficacy and safety of Entacapone combined with Madopar (levodopa/benserazide) in the treatment of early-stage Parkinson's disease (PD) among Chinese patients. The study will enroll patients diagnosed with PD according to the MDS criteria, aged 18-80, with modified Hoehn-Yahr stages 1-2.5, and who have not previously used Entacapone. Participants will be assigned to two groups based on their prior treatment history: the LBE group (levodopa/benserazide/entacapone) or the LB group (levodopa/benserazide only), according to their actual clinical treatment plan.

The study will observe patients over a 24-week period, evaluating changes in motor symptoms using the MDS-UPDRS Part III score as the primary endpoint. Secondary outcomes include assessments of daily living abilities, motor complications, quality of life (PDQ-39), cognitive function (MMSE), global impression (CGI), and safety profiles, including adverse event reporting.

This study does not involve any interventional treatment changes; all therapeutic decisions remain at the discretion of the treating physicians. The findings are expected to provide real-world evidence regarding the potential benefits and safety of adding Entacapone to Madopar in the management of early PD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an observational, multicenter, case-control study designed to evaluate the efficacy and safety of Entacapone combined with Madopar (Levodopa/Benserazide, LB) in the treatment of early-stage Parkinson's disease (PD) in Chinese patients. The study is conducted across multiple centers in China and includes patients diagnosed with PD according to the MDS criteria, aged 18-80 years, with a modified Hoehn-Yahr stage of 1-2.5. Participants will be divided into two groups based on their actual clinical treatment: (1) the LBE group (Levodopa/Benserazide/Entacapone) and (2) the LB group (Levodopa/Benserazide only). The study does not involve any randomization, blinding, or intervention allocation; instead, it reflects real-world clinical practice, where all treatment decisions are made solely by the attending physician.

The study will observe patients over a 24-week period to compare the effectiveness of the two treatment strategies in improving motor symptoms, daily living activities, and quality of life, as well as the incidence of adverse events. The primary outcome measure is the change in MDS-UPDRS Part III (motor examination) score from baseline to Week 24. Secondary outcomes include changes in MDS-UPDRS Part II (activities of daily living), Part IV (motor complications), total MDS-UPDRS II+III scores, PDQ-39 quality of life scores, Clinical Global Impression (CGI) scores, MMSE cognitive scores, and modified Hoehn-Yahr staging. Safety assessments include adverse events, serious adverse events, vital signs, laboratory tests, and ECG findings.

All treatments, including medication selection, dosage, and adjustment, will follow the treating physician's routine clinical judgment, and no intervention or modification by the study team will occur. Concomitant medications such as amantadine, anticholinergics, dopamine agonists, and MAO-B inhibitors (e.g., selegiline, rasagiline) are allowed if their doses are stable for at least 30 days before enrollment and remain unchanged throughout the study period.

The estimated sample size is 216 participants, with approximately 108 in each group, allowing for a 10% dropout rate. The study is expected to start in June 2025 and complete by April 2027, with final data analysis by June 2027. The results of this study aim to provide real-world evidence regarding the potential benefits and safety of Entacapone combined with Madopar in the early-stage PD population in China.

Study Type

Observational

Enrollment (Estimated)

216

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Yousheng Xiao, PhD
  • Phone Number: +86-15177196935
  • Email: xys135@126.com

Study Locations

  • China
    • Guanxi
      • Nanning, Guanxi, China, 530021
        • Recruiting
        • The First Affiliated Hospital of Guangxi Medical University
        • Contact:
          • Yousheng Xiao Yousheng Xiao, MD
          • Phone Number: +86 15177196935
          • Email: xys135@126.com
        • Principal Investigator:
          • Yousheng Xiao, MD
        • Sub-Investigator:
          • Binru Li, MMed
        • Sub-Investigator:
          • Huadan Yang, MMed
        • Sub-Investigator:
          • Huaxin Huang, MBBS
        • Sub-Investigator:
          • Lingyue Liang, MBBS
        • Sub-Investigator:
          • Li Wang, MD
        • Sub-Investigator:
          • Jiang Lei, MMed

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study will enroll adult patients diagnosed with Parkinson's disease according to MDS criteria, aged between 18 and 80 years, and in the early stages of the disease (modified Hoehn-Yahr stage 1-2.5). Participants must have a Mini-Mental State Examination (MMSE) score ≥26 and a Beck Depression Inventory (BDI) score <15. Eligible patients will include those who are either levodopa-naïve or have been on a stable dose of levodopa (300-600 mg/day) for at least one month. All participants must voluntarily agree to join the study, provide informed consent, and be able to comply with the study protocol.

Description

Inclusion Criteria:

Age between 18 and 80 years;

Diagnosed with Parkinson's Disease based on the MDS criteria, confirmed by a movement disorder neurologist;

Modified Hoehn and Yahr stage between 1 and 2.5;

No prior use of entacapone;

MMSE score ≥ 26;

BDI (Beck Depression Inventory) score < 15;

Either:

Has never used levodopa before, or

Has been on a stable dose of levodopa (300-600 mg/day) for at least 1 month prior to enrollment;

Stable doses of amantadine, anticholinergics, dopamine agonists, selegiline, or rasagiline are allowed if maintained for at least 30 days prior to and during the study;

Willing and able to give informed consent and comply with study procedures, with caregiver support if needed.

Exclusion Criteria:

Previous use of entacapone or tolcapone for more than 30 days, or within 4 weeks before baseline;

Use of dopamine agonists within 4 weeks before baseline;

BDI score ≥ 15;

MMSE score < 26;

Unstable levodopa dosage;

History of dyskinesia;

Diagnosis of atypical or secondary parkinsonism, or history of PD-related neurosurgery;

Clinically significant medical conditions within the past 5 years that could interfere with study participation;

Use of medications known to induce parkinsonism;

Participation in other investigational drug trials within 30 days before baseline.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Madopar Group
Participants in this group will receive Madopar (levodopa/benserazide) as part of their routine clinical treatment. Treatment decisions, including dosage and frequency, will be made by the treating physician according to the patient's clinical condition. The typical treatment for levodopa-naïve patients is Madopar 100/25 mg taken three times daily (TID) for 24 weeks. For patients already on levodopa therapy, the physician may continue the current Madopar dosage as part of routine care. This is an observational study, and no specific interventions are assigned by the study.
Entacapone + Madopar Group
Participants in this group will receive Entacapone (200 mg) in combination with Madopar (levodopa/benserazide, typically 100/25 mg) as part of their routine clinical treatment. The typical regimen is Entacapone 200 mg administered three times daily (TID), or at a frequency matching the patient's levodopa dosing schedule, as determined by the treating physician based on the patient's clinical condition. The study is observational in nature, and no specific intervention is assigned by the study team. All treatment decisions, including drug type, dosage, and frequency, are made by the treating physician as part of routine care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline to Week 24 in the MDS-UPDRS Part III (Motor Examination) score
Time Frame: Baseline to Week 24
The MDS-UPDRS Part III (Motor Examination) assesses the motor function of patients with Parkinson's disease. The total score ranges from 0 to 132, with higher scores indicating greater motor impairment. The change from baseline to Week 24 will be analyzed to evaluate treatment efficacy.
Baseline to Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline to Week 24 in the MDS-UPDRS Parts II and III total score
Time Frame: Baseline to Week 24
he MDS-UPDRS Part II assesses activities of daily living (maximum score: 52) and Part III assesses motor function (maximum score: 132). The combined total score (range: 0-184) reflects overall functional impairment, with higher scores indicating greater disability.
Baseline to Week 24
Change from baseline to Week 24 in the MDS-UPDRS Part II (Activities of Daily Living) score
Time Frame: Baseline to Week 24
The MDS-UPDRS Part II evaluates the impact of Parkinson's disease on activities of daily living (ADL), such as speech, handwriting, dressing, and walking. The total score ranges from 0 to 52, with higher scores indicating greater disability. The score change from baseline to Week 24 will be analyzed to assess treatment effectiveness on daily functioning.
Baseline to Week 24
Change from baseline to Week 24 in the MDS-UPDRS Part IV score
Time Frame: Baseline to Week 24
The MDS-UPDRS Part IV evaluates motor complications including dyskinesia and wearing-off phenomena. Changes in the score from baseline to Week 24 will be analyzed to assess treatment-related motor complications.
Baseline to Week 24
Change from baseline to Week 24 in the PDQ-39 summary index score
Time Frame: Baseline to Week 24
The Parkinson's Disease Questionnaire-39 (PDQ-39) assesses health-related quality of life across 8 domains. The summary index score reflects the overall impact of Parkinson's disease on quality of life, with higher scores indicating worse outcomes.
Baseline to Week 24
Change from baseline to Week 24 in the Clinical Global Impression (CGI) score
Time Frame: Baseline to Week 24
The Clinical Global Impression (CGI) scale is used by both investigators and participants to rate overall disease severity and clinical improvement. The score change from baseline to Week 24 will be used to assess perceived treatment effectiveness.
Baseline to Week 24
Change in modified Hoehn-Yahr stage from baseline to Week 24
Time Frame: Baseline to Week 24
The modified Hoehn-Yahr staging scale evaluates the severity and progression of Parkinson's disease, with higher stages indicating more advanced disease. Stage change from baseline to Week 24 will be used to assess disease progression or stability.
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yousheng Xiao

Collaborators

Jiangbin Hospital of Guangxi Zhuang Autonomous Region
Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University
Guangxi International Zhuang Medicine Hospital
Ethnic Hospital of Guangxi Zhuang Autonomous Region

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 5, 2025

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

June 30, 2027

Study Registration Dates

First Submitted

March 22, 2025

First Submitted That Met QC Criteria

April 8, 2025

First Posted (Actual)

April 15, 2025

Study Record Updates

Last Update Posted (Actual)

June 24, 2025

Last Update Submitted That Met QC Criteria

June 18, 2025

Last Verified

June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EMPD-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

The decision to share individual participant data (IPD) is currently under review and will depend on ethical approvals, data use agreements, and institutional policy.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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