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

NCT ID: NCT06928519

Last Updated: 2025-06-24

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 216 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-06-05
• Study Completion Date: 2027-06-30

Brief Summary

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.

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.

Conditions

Parkinson Disease (PD)

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangbin Hospital of Guangxi Zhuang Autonomous Region

UNKNOWN

Sponsor Role: collaborator

Guangxi International Zhuang Medicine Hospital

UNKNOWN

Sponsor Role: collaborator

Ethnic Hospital of Guangxi Zhuang Autonomous Region

UNKNOWN

Sponsor Role: collaborator

Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University

UNKNOWN

Sponsor Role: collaborator

Yousheng Xiao

OTHER

Sponsor Role: lead

Responsible Party

Yousheng Xiao

Professor and Chief Physician, Department of Neurology, The First Affiliated Hospital of Guangxi Medical University

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guanxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yousheng Xiao, PhD

Role: CONTACT

xys135@126.com

+86-15177196935

Facility Contacts

Yousheng Xiao Yousheng Xiao, MD

Role: primary

xys135@126.com

+86 15177196935

References

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Reference Type: BACKGROUND

PMID: 20582993 (View on PubMed)

Fung VS, Herawati L, Wan Y; Movement Disorder Society of Australia Clinical Research and Trials Group; QUEST-AP Study Group. Quality of life in early Parkinson's disease treated with levodopa/carbidopa/entacapone. Mov Disord. 2009 Jan 15;24(1):25-31. doi: 10.1002/mds.21878.

Reference Type: BACKGROUND

PMID: 18846551 (View on PubMed)

Lew MF, Somogyi M, McCague K, Welsh M; Lce QoL Study Group. Immediate versus delayed switch from levodopa/carbidopa to levodopa/carbidopa/entacapone: effects on motor function and quality of life in patients with Parkinson's disease with end-of-dose wearing off. Int J Neurosci. 2011 Nov;121(11):605-13. doi: 10.3109/00207454.2011.598982. Epub 2011 Aug 16.

Reference Type: BACKGROUND

PMID: 21843110 (View on PubMed)

Tolosa E, Hernandez B, Linazasoro G, Lopez-Lozano JJ, Mir P, Marey J, Kulisevsky J. Efficacy of levodopa/carbidopa/entacapone versus levodopa/carbidopa in patients with early Parkinson's disease experiencing mild wearing-off: a randomised, double-blind trial. J Neural Transm (Vienna). 2014 Apr;121(4):357-66. doi: 10.1007/s00702-013-1114-x. Epub 2013 Nov 20.

Reference Type: BACKGROUND

PMID: 24253234 (View on PubMed)

Hauser RA, Panisset M, Abbruzzese G, Mancione L, Dronamraju N, Kakarieka A; FIRST-STEP Study Group. Double-blind trial of levodopa/carbidopa/entacapone versus levodopa/carbidopa in early Parkinson's disease. Mov Disord. 2009 Mar 15;24(4):541-50. doi: 10.1002/mds.22343.

Reference Type: BACKGROUND

PMID: 19058133 (View on PubMed)

Liao X, Wu N, Liu D, Shuai B, Li S, Li K. Levodopa/carbidopa/entacapone for the treatment of early Parkinson's disease: a meta-analysis. Neurol Sci. 2020 Aug;41(8):2045-2054. doi: 10.1007/s10072-020-04303-x. Epub 2020 Mar 11.

Reference Type: BACKGROUND

PMID: 32162166 (View on PubMed)

Kuoppamaki M, Leinonen M, Poewe W. Efficacy and safety of entacapone in levodopa/carbidopa versus levodopa/benserazide treated Parkinson's disease patients with wearing-off. J Neural Transm (Vienna). 2015 Dec;122(12):1709-14. doi: 10.1007/s00702-015-1449-6. Epub 2015 Sep 7.

Reference Type: BACKGROUND

PMID: 26347184 (View on PubMed)

Related Links

https://pubmed.ncbi.nlm.nih.gov/

Entacapone combined with levodopa/benserazide or levodopa/carbidopa in early Parkinson's disease.

Other Identifiers

EMPD-001

Identifier Type: -

Identifier Source: org_study_id