A Phase 2 study to assess the safety and efficacy of SUL-238 in patients with early, untreated Parkinson’s Disease

Prior treatment

• Received or used an investigational product (including placebo) or device within the following time period prior to day -1 in the current study: 90 days, 5 half-lives, or twice the duration of the biological effect of the investigational product (whichever is longer).
• Use of non-prescription drugs, vitamins, herbal, and dietary supplements which has potential to influence the mitochondrial function (such as coenzyme Q10, carnitine, creatine, lipoic acid and vitamin E) within 30 days prior to day -1.

Other illness

• Atypical parkinsonism, including that due to drugs, metabolic disorders, encephalitis, cerebrovascular disease, normal pressure hydrocephalus, or other neurodegenerative disease.
• History of clinically significant sensitivity to any of the study medications, or components thereof or a history of drug or other allergies that, in the opinion of the Investigator or Medical Monitor, contraindicates their participation.
• A history or presence of any disease, condition, or surgery likely to affect drug absorption, distribution, metabolism, or excretion. Patients with a history of cholecystectomy should be excluded.
• Any history of intellectual disability or psychiatric disorders, including substance use disorders, according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, except a history of mild depression/anxiety that has been resolved for at least the past 3 months.
• A positive Hepatitis B surface antigen, Hepatitis C antibody, or Human Immunodeficiency Virus (HIV) antibody test at screening.

Lab values

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 1.5 times the upper limit of normal (ULN) at screening or between screening and first dose administration.

Other

• Women with a positive pregnancy test, are lactating, or are planning to become pregnant during the study or within 6 months of the end of this study.
• A Columbia-Suicide Severity Rating Scale (C-SRRS) score of >3 at screening.
• A history or presence of a clinically significant hepatic, renal, gastrointestinal, cardiovascular, endocrine, pulmonary, ophthalmologic, immunologic, hematologic, dermatologic, or neurologic (other than PD) abnormality.
• At screening, any clinically significant abnormalities in rhythm, conduction, or morphology of the resting 12-lead ECG.
• A clinically significant vital signs abnormality at screening or day -1, as determined by the investigator in accordance with the Dutch General Practitioner Guidelines (NHG Standards), corresponding to higher than 160 mm Hg systolic and 110 mm Hg diastolic blood pressure. Participants with a systolic blood pressure <90 mmHg or a diastolic blood pressure <50 mmHg will also be excluded.
• In the opinion of the Investigator or Medical Monitor, the patient is unlikely to comply with the protocol or is unsuitable for any reason, e.g., known issues with ability to swallow tablets.
• Women of child-bearing potential, or men, who are unwilling or unable to use accepted methods of birth control for up to 6 months following study participation.
• Contraindications for undergoing an MRI.

• Untreated Parkinson's Disease patients diagnosed in accordance with the UK PDS Brain Bank Criteria for the diagnosis of Parkinson's Disease. Patients must have bradykinesia and at least one of the following: a. muscular rigidity b. rest tremor (4–6 Hz) c. postural instability unrelated to primary visual, cerebellar, vestibular or proprioceptive dysfunction.
• Women of non-childbearing potential must be post-menopausal (the last menstrual period was at least 12 months ago, and follicle-stimulating hormone [FSH] at screening confirms post-menopausal status), or have no uterus, ovaries, or fallopian tubes (or have their fallopian tubes tied). All women must have a negative pregnancy test result before administration of test article. Women who are surgically sterile must provide documentation of the procedure by an operative report or by ultrasound.
• The duration of Parkinson's Disease since diagnosis is ≤ 1 year.
• Patients with Modified Hoehn and Yahr stage ≤ 2.0.
• Patients with Montreal Cognitive Assessment (MOCA) score of ≥22
• Men and women aged ≥40 years at screening.
• Able to understand the nature of the study and provide signed and dated written informed consent in accordance with local regulations before the conduct of any study related procedures.
• Able to complete all study related testing and evaluations.
• Patients must be, in the opinion of the Investigator, able to participate in all scheduled evaluations, likely to complete all required tests, and likely to be compliant.
• Men and women of child-bearing potential with partners of child-bearing potential must agree to use highly effective contraception. For male patients, contraception should continue for 3 months after the last dose of investigational medicinal product (IMP, one spermatic cycle). For female patients, contraception should continue for 6 months after the last dose of IMP (one oocyte cycle). Male and female patients must refrain from sperm or oocyte donation in this period.