A Study to Evaluate the Efficacy, PK, Safety, and Tolerability of VIM0423 in Adults With Parkinson's Disease Tremor Insufficiently Responsive to Dopaminergic Therapy

Parkinson's disease (PD) is the second most common neurodegenerative condition, with studies estimating US prevalence among individuals aged 45 years and older rising to approximately 1,238,000 by 2030. More than 75% of individuals with PD will experience resting tremor at some point during their disease course, and approximately 60% additionally suffer from a symptomatic tremor during action or movement, complicating functional tasks.

The distress caused by PD tremor is profound, with individuals consistently identifying it as their "most bothersome" symptom in early disease, and more impactful than other motor and nonmotor symptoms. Despite the clear importance of this symptom to patient experience, significant unmet need in tremor management persists. Tremor-specific efficacy of dopaminergic therapy, the mainstay of early PD pharmacology, is often inconsistent or incomplete, giving rise to the clinical concept of "dopamine-responsive" versus "dopamine-refractory" tremor. Anti-tremor efficacy of anticholinergic agents has been recognized for decades; however, their clinical utility is limited by both central and peripheral adverse effects VIM0423 is being developed as an oral medication designed to improve the central and peripheral tolerability seen with other anticholinergic medications.

Vista PD (Study VIM0423-251) is a Phase 2, multicenter study designed to assess the efficacy, PK, safety, and tolerability of VIM0423 in adults with Parkinson's disease tremor insufficiently responsive to dopaminergic therapy. Up to 80 individuals will be enrolled in the trial.

Cohort 1 will be comprised of adults diagnosed with PD who are on stable and adequate dopaminergic therapy (oral levodopa or oral dopamine agonist only), with residual tremor. Participants in Cohort 1 will be randomized (1:1) to receive either VIM0423 or matching placebo (up to 5 pills a day[MO1.1][TG1.2][MO1.3], taken once daily) for 7 weeks. The Investigator and Participant will not know whether [MO2.1]patients are receiving VIM0423 or placebo, but that information will be available if needed.

Cohort 2 will be comprised of adults diagnosed with PD who are dopaminergic naïve, as defined by: no prior or ongoing usage of levodopa (in any form) or dopamine agonist (in any form), and no anticipated plans to initiate said therapies for the duration of the study. Participants in Cohort 2 will be randomized (1:1) to receive either VIM0423 or matching placebo (up to 5 pills a day[MO3.1], taken once daily) for 7 weeks. The Investigator and Participant will not know whether patients are receiving VIM0423 or placebo, but that information will be available if needed.

The total time of participation in the trial is up to 12 weeks and requires 6 in person visits. The study schedule includes Screening and Baseline (up to 4 weeks, 2 visits), Treatment period (including taper, 7 weeks, 3 Visits), and Safety follow-up (1 week, 1 Visit).

Assessments of changes in Parkinson's disease will be made by study personnel. Clinical labs, EKGs, and Adverse events will be monitored throughout the study. Participants will be asked to use a wearable device during the study and perform self-assessments of their Parkinson's tremor and its impact on their activities of daily living.

Inclusion criteria

• Participant must be male or nonpregnant female between 18 and 65 years of age (inclusive) at Visit 1 (Screening).
• Diagnosis of clinically probable or clinically established idiopathic Parkinson's disease (PD) at Visit 1 (Screening) established by the MDS 2015 criteria which must include tremor as one of the cardinal characteristics.
• Cohort 1: Currently using levodopa (any oral form only) or oral dopamine agonist at a stable dose and regimen of at least 10 weeks prior to Visit 1 (Screening); with no anticipated changes to said therapies for the duration of the study; and on a minimum of 300 mg LEDD. Cohort 2: Individuals who are dopaminergic naïve, as defined by: no prior or ongoing usage of levodopa (in any form) or dopamine agonist (in any form), and no anticipated plans to initiate said therapies for the duration of the study.
• The participants must meet protocol-specified requirements for baseline tremor scores.

Exclusion criteria

• Currently (within 7 days of Screening) taking any anticholinergic medication.
• Prior deep brain stimulation (DBS) or any other form of invasive neurosurgical intervention (including, but not limited to, magnetic resonance-guided focused ultrasound thalamotomy, ablative thalamotomy, gamma knife thalamotomy)

Other protocol-specified inclusion and exclusion criteria may apply.