ENTACAPONE | LEVODOPA | CARBIDOPA MONOHYDRATE for Parkinson's disease

Inclusion criteria

• {"criterion_text":"- 1. Understand and voluntarily sign an informed consentdocument prior to any study related assessments/procedures.\n- 2. Able to adhere to the study visit schedule and other protocolrequirements.\n- 3. Female Subject of childbearing potential1 and malesubjects with female partner of childbearing potential1 iswilling to use highly effective contraceptive methods during thestudy (adequate: combined hormonal contraceptionassociated with inhibition of ovulation, progestogen-onlyhormonal contraception associated with inhibition ofovulation, intrauterine device, intrauterine hormone-releasingsystem, bilateral tubal occlusion, vasectomized partner2,sexual abstinence3).1 For the purpose of this document, a female is considered of childbearing potential(FCBP), i.e. fertile, following menarche and until becoming post-menopausal unlesspermanently sterile. Permanent sterilisation methods include hysterectomy,bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state isdefined as no menses for 12 months without an alternative medical cause. A highfollicle stimulating hormone (FSH) level in the postmenopausal range may be usedto confirm a post-menopausal state in women not using hormonal contraceptionor hormonal replacement therapy. However in the absence of 12 months ofamenorrhea, a single FSH measurement is insufficient. For the purpose of thisdocument, a man is considered fertile after puberty unless permanently sterile bybilateral orchidectomy2 Vasectomized partner is a highly effective birth control method provided thatpartner is the sole sexual partner of the WOCBP trial participant and that thevasectomized partner has received medical assessment of the surgical success3 In the context of this guidance sexual abstinence is considered a highly effectivemethod only if defined as refraining from heterosexual intercourse during theentire period of risk associated with the study treatments. The reliability of sexualabstinence needs to be evaluated in relation to the duration of the clinical trial andthe preferred and usual lifestyle of the subject.\n- 4. All subjects must agree not to share medication.\n- 5. Diagnosis of Idiopathic PD, inclusive of familial PD andgenetic forms of L-Dopa responsive PD\n- 6. Age 18 - 75 years\n- 7. Age at Parkinson’s disease onset before 65 years\n- 8. Disease duration ≥ 5 years\n- 9. Oral medication constant for four weeks prior to baselinevisit\n- 10. Oral treatment with L-Dopa and non-ergot dopamineagonist(s) (any preparation, any dosage)\n- 11. Presence of dopaminergic motor fluctuations based onpatient history\n- 12. Presence of dopaminergic neuropsychiatric (affective)fluctuations based on patient history\n- 13. Presence of behavioural hyperdopaminergic syndromeincluding clinically relevant neuropsychiatric behaviouralabnormalities according Ardouin Behavioural Scale Section 1,hypomanic symptoms, psychosis + Section 4 hyperdopaminergicbehaviours (score ≥ 3), eventually further accompanied by impulsecontrol disorders, a/o dopamine dysregulation, syndrome, a/ohallucination – psychosis spectrum; in case symptoms of thehallucination/psychosis or hypomania-mania spectrum are present,retained insight is mandatory at the time of study enrolment"}
• {"criterion_text":"- Preserved dopaminergic motor response of ≥ 30% accordingto MDS UPDRS III assessed in the practically defined dopaminergicOff and On conditions"}

Exclusion criteria

• {"criterion_text":"- 1. Women during pregnancy and lactation.\n- 2. History of hypersensitivity to the investigational medicinalproduct or to any drug with similar chemical structure or to anyexcipient present in the pharmaceutical form of the investigationalmedicinal product.\n- 3. Participation in other clinical trials or observation period ofcompeting trials over the past three months\n- 4. Patients suffering from cognitive impairment (MoCA < 21)will be excluded for the major reason to obtain valid Ardouinassessments that will be hampered in case cognitive impairment(and therefore insight) is too severe\n- 5. Acute paranoid psychosis without retained insight (howeverimpulse control disorder or dopamine dysregulation syndrome arenot an exclusion criterion; illusions or (pseudo)-hallucinations arenot an exclusion criterion as long as there is no endangerment ofthe patients themselves or other persons owing to clinicaljudgement; patients may be eligible after remission ofpsychosis/suicidality)\n- 6. Severe depression according to ICD-10 criteria; however,affective fluctuations with intermittent depressive symptoms(reversed by dopaminergic medication) are not an exclusioncriterion\n- 7. Active suicidality without self-distancing (however, suicidalideation/thoughts or passive wishes of being dead are not anexclusion criterion as long as the patient is credibly distancing fromit).\n- 8. General contraindications for intestinal L-Dopa therapy(according to Lecigon® Fachinformation)\n- 9. Gastrointestinal contraindications against PEG-J tubeplacement or TPort placement\n- 10. Tremor-dominant PD without dopaminergic responsefluctuations;\n- 11. Pre-existing device assisted therapy (DAT) immediatelybefore study enrolment including with DBS, LCIG/LECIG, orsubcutaneous therapy with apomorphine or foslevodopa; if patientterminated pre-existing subcutaneous therapy, the patient will beeligible after having received oral dopamine replacement therapyfor at least 3 months\n- 12. Malignancy in a non-remitted stage"}
• {"criterion_text":"- History of entacapone-induced diarrhoea under oralentacapone (it is recommended to have tried oral entacaponebefore entering this study, but this is not mandatory)"}

Primary endpoints

• {"endpoint_text":"- To show superiority of LECIG therapy compared to best medicaltreatment on “hyperdopaminergic symptoms” corresponding toSection 1 (items 2 & 4), and section 4 (all items) of the “ArdouinBehavioural Scale” between pre-interventional baseline and 6-month follow-up","definition_or_measurement_approach":"Measured using the Ardouin Behavioural Scale (Section 1 items 2 & 4 and Section 4 all items), comparing scores between pre-interventional baseline and 6-month follow-up to assess change in hyperdopaminergic symptoms."}

Germany

Earliest CTIS Part Ii Submission Date

21-07-2025

Latest Decision Or Authorization Date

16-04-2026

Processing Time Days

269

Number Of Sites

8

Number Of Participants

150

Primary sponsor

Full Name

Universitaetsklinikum Tuebingen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany

Contract research organisations

Name

Universitaetsklinikum Tuebingen AöR

Responsibilities

Listed as CRO contact (public and scientific contact), functional email zks-pm@med.uni-tuebingen.de