Evaluation of Fasudil Hydrochloride Safety, Tolerability, and Efficacy in Idiopathic Parkinson's Disease Patients

The primary objective of this clinical study is to establish the combined **safety** and **tolerability** profile of oral Fasudil solution over a 22-day period in patients with **Idiopathic Parkinson's Disease**. This is clinically relevant as it aims to assess the potential of Fasudil, a Rho Kinase inhibitor, to be safely administered to patients, which could lead to new therapeutic options for managing symptoms of Parkinson's Disease. The study does not list any secondary objectives.

The clinical trial involves participants diagnosed with **Idiopathic Parkinson's Disease**. The study population includes both male and female subjects, aged between 30 and 80 years, who are non-fluctuating and stable on symptomatic Parkinson's Disease medication for at least six weeks. Participants must be at Hoehn & Yahr stages 1 to 3 and meet the Movement Disorder Society criteria for at least probable Parkinson's Disease. Women of childbearing potential are required to be non-lactating and either surgically sterile or using a highly effective method of birth control, with a negative pregnancy test. The trial population is selected based on their ability to thoroughly understand all information provided and give full informed consent according to Good Clinical Practice (GCP). The sponsor has not provided information regarding the total number of participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, indicating additional ethical considerations in the study design.

The clinical trial is designed to evaluate the **safety** and **tolerability** of oral **fasudil hydrochloride** in patients with **Idiopathic Parkinson's Disease**. This study is a randomized, double-blind, controlled trial, conducted over a period of 22 days. Participants will be randomly assigned to receive either a high dose or a low dose of fasudil hydrochloride, or a placebo, administered as an oral solution. The trial aims to assess the combined occurrence of intolerance and treatment-related serious adverse events (SAEs) as primary endpoints, with secondary endpoints including changes in the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), PD Quality of Life Scale (PDQ-8), and other relevant measures.

The sequence of study visits includes an initial screening visit to confirm eligibility based on criteria such as age, disease stage, and stability on current medication. Following the screening, participants will undergo a baseline visit where initial assessments are conducted. Subsequent follow-up visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. The end-of-study visit will involve comprehensive evaluations to conclude the participant's involvement in the trial. The expected length of participant involvement is approximately 22 days, with an additional follow-up period extending to day 50 for certain assessments.

Participants may be subject to early termination from the study if they experience significant treatment-related adverse events or if they withdraw consent. The trial is conducted in compliance with Good Clinical Practice (GCP) guidelines, ensuring that all participants provide informed consent prior to enrollment. The study's recruitment period began on September 11, 2023, and is expected to conclude by February 8, 2025, with the trial estimated to end on September 30, 2024. The trial status is currently halted as of February 12, 2025, pending further evaluation.

The clinical trial involves the administration of two experimental medications, both containing the active substance **fasudil hydrochloride**, which is a chemical inhibitor of Rho Kinase. The first experimental medication is named ROCK_PD_high_dose and is provided in the form of an **oral solution**. The maximum daily dose for this formulation is 88 mg, with a total maximum dose of 1848 mg over a treatment period of 22 days. The medication is administered orally, and the dosing schedule is designed to ensure consistent delivery of the active substance throughout the trial period. Participant compliance is monitored through regular assessments and documentation of dosing adherence.

The second experimental medication, ROCK_PD_low_dose, also contains **fasudil hydrochloride** and is similarly provided as an **oral solution**. This formulation has a maximum daily dose of 44 mg and a total maximum dose of 924 mg over the same 22-day treatment period. The administration route is oral, and the dosing frequency is structured to maintain therapeutic levels of the active substance. Compliance with the dosing regimen is tracked to ensure accurate data collection and analysis.

In addition to the experimental treatments, the study includes a comparator treatment, Quinina Labesfal 250 mg/ml, which contains the active substance **quinine dihydrochloride**. This comparator is provided as a **solution for injection**. The maximum daily dose is 2 ml, with a total maximum dose of 42 ml over the 22-day period. The solution is diluted with 30 ml of 40% glucose solution immediately before use, and the administration is conducted orally. The comparator serves as a control to evaluate the efficacy and safety of the experimental medications. Compliance with the administration protocol is monitored to ensure the integrity of the trial results.

The efficacy of the clinical trial evaluating the **ROCK-Inhibitor Fasudil** in patients with Parkinson's Disease will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the combined occurrence of intolerance, defined as the termination of treatment due to treatment-related adverse events (AEs), and the occurrence of self-reported and pre-defined treatment-related serious adverse events (SAEs), measured from day 1 to day 22.

Secondary endpoints include several measures: the occurrence of intolerance and treatment-related SAEs over different time frames, changes in the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I to IV, changes in the 8-item Parkinson's Disease Quality of Life Scale (PDQ-8), changes in the Parkinson's Disease Non-Motor Symptom Questionnaire (NMSQuest), changes in the Montreal Cognitive Assessment (MoCA), changes in the Beck's Depression Inventory-II (BDI-II), and the Global Impression of Improvement scores (CGI-I for clinicians and PGI-I for patients). These secondary endpoints will be evaluated at various time points, including day 10, day 22, and day 50, depending on the specific measure.