Evaluation of Intestinal Gel Therapy with Levodopa, Entacapone, and Carbidopa Monohydrate in Parkinson's Disease to Mitigate Dopaminergic Desensitization and Neuropsychiatric Complications

The primary objective of the study is to demonstrate the superiority of **LECIG** therapy, which combines intestinal **levodopa** and **entacapone**, over the best medical treatment in addressing "hyperdopaminergic symptoms" in patients with **Parkinson's disease**. This will be assessed using the Ardouin Behavioural Scale, specifically focusing on Section 1 (items 2 & 4) and Section 4 (all items), comparing pre-interventional baseline data with a 6-month follow-up. The clinical relevance of this objective lies in its potential to improve the management of neuropsychiatric complications associated with Parkinson's disease, thereby enhancing patient outcomes.

Secondary objectives include the evaluation of various scales and measures to assess different aspects of the disease and its impact: - Neuropsychiatric fluctuation scale - QUIP rating scale (QUIP-RS) for impulse control disorders - Apathy Evaluation Scale for apathy outcomes - Measures of motor sensitization/desensitization, motor fluctuations, and dyskinesia using MDS-UPDRS IV, Unified Dyskinesia Rating Scale (UDysRS), and MDS-UPDRS III - Quality of life assessment using PDQ-39 - Patient/physician global impression - Caregiver burden

The clinical trial involves participants diagnosed with **Parkinson's Disease**, specifically targeting individuals with idiopathic forms, including familial and genetic variants responsive to L-Dopa. The study population comprises both male and female subjects, aged between 18 and 75 years, with the onset of Parkinson's disease occurring before the age of 65. Participants must have a disease duration of at least five years and have maintained a constant oral medication regimen for four weeks prior to the baseline visit. The trial does not include a vulnerable population. Participants are required to have dopaminergic motor and neuropsychiatric fluctuations, as well as behavioral hyperdopaminergic syndrome, which includes neuropsychiatric behavioral abnormalities as per the Ardouin Behavioural Scale. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **Lecigon**, an **intestinal gel** containing **entacapone, levodopa, and carbidopa monohydrate**, in managing symptoms of **Parkinson's disease**. This study is a randomized, double-blind, controlled trial, classified as a low-intervention clinical trial due to the use of authorized medicinal products in accordance with their marketing authorization. The trial aims to demonstrate the superiority of Lecigon therapy over the best medical treatment in reducing hyperdopaminergic symptoms, as measured by the Ardouin Behavioural Scale, over a six-month period. The trial is expected to commence recruitment in October 2025 and conclude by October 2030, with a maximum treatment period of 12 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, disease duration, and current medication regimen. Following successful screening, participants will be randomized to receive either Lecigon or the best oral medical treatment. Study visits will occur at regular intervals to monitor treatment efficacy and safety, with assessments including the Ardouin Behavioural Scale and other relevant clinical evaluations. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted to evaluate the long-term effects of the treatment.

Participant involvement is expected to last up to 12 months, with conditions for early termination including non-compliance with study protocols, adverse events, or withdrawal of consent. The trial will adhere to ethical standards, ensuring informed consent is obtained from all participants prior to any study-related procedures. The study's primary endpoint is the reduction of hyperdopaminergic symptoms, with no secondary endpoints specified. The trial's design and methodology are structured to provide robust data on the therapeutic potential of Lecigon in managing Parkinson's disease symptoms.

The clinical trial involves the administration of **Lecigon**, an **intestinal gel** formulation containing the active substances **entacapone**, **levodopa**, and **carbidopa monohydrate**. The pharmaceutical form is specifically designed for **intestinal use**, ensuring targeted delivery and absorption. The concentration of the active substances in the gel is 20 mg/ml of entacapone, 5 mg/ml of levodopa, and 20 mg/ml of carbidopa monohydrate. The maximum daily dose is set at 100 ml, with a total maximum dose of 54,000 ml over the treatment period. The administration is continuous, and the treatment period is capped at 12 months. The gel is produced by Lobsor Pharmaceuticals AB and is not a pediatric formulation.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the efficacy and safety of the Lecigon gel in managing symptoms associated with Parkinson's disease. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial aims to demonstrate the superiority of Lecigon therapy in addressing hyperdopaminergic symptoms, as measured by specific sections of the Ardouin Behavioural Scale, between the pre-interventional baseline and a 6-month follow-up.

The efficacy of the clinical trial titled "INITIATE-LECIG: Intestinal levodopa + entacapone therapy (Lecigon®) to counteract dopaminergic desensitization and neuropsychiatric complications in Parkinson’s disease" will be assessed by evaluating the superiority of LECIG therapy compared to the best medical treatment. The primary endpoint focuses on the improvement of **hyperdopaminergic symptoms**. These symptoms are measured using the "Ardouin Behavioural Scale," specifically targeting Section 1 (items 2 & 4) and Section 4 (all items). The assessment will compare the scores between the pre-interventional baseline and the 6-month follow-up.