A Randomized, Double-Blind, Placebo-Controlled Trial of IkT-148009 in Untreated Parkinson's Disease

Prior treatment

• Previous procedure or surgery for PD, or anticipation of these during the study
• Clinically significant hallucinations requiring antipsychotic use in the 12 months prior to Screening
• Past treatment with levodopa, dopaminergic agonists, monoamine oxidase-B inhibitors, supplements containing levodopa (i.e. Mucana pruriens), or A2A antagonists for more than 28 days, or treatment with any of these medications or supplements within 28 days prior to screening
• Past treatment with irreversible monoamine oxidase-B inhibitors (e.g., selegiline) for more than 28 days; must be discontinued for at least 90 days before screening
• Currently receiving moderate or strong Cytochrome P450 (CYP) 3A4/5 inducers or CYP3A4/5 inhibitors (except for topical administration)
• Currently receiving any antipsychotic, metoclopramide, reserpine, or amphetamine.
  • Prior/Concurrent Clinical Study Experience:
• Current participation in another investigational clinical trial and/or receipt of any investigational medication within 90 days prior to screening
• Previous randomization into this or another IkT-148009 study
  • Diagnostic Assessments:
• Active suicidal ideation within one year prior to screening visit, as determined by the Columbia Suicide Rating Scale (answer of "yes" on question 4 or 5)
• Medical or recreational use of marijuana in the 3 months prior to the screening visit

Other illness

• Current diagnosis or history of substance abuse (excluding nicotine or caffeine) by Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria
• Any skin condition that would interfere with obtaining adequate samples

Lab values

• Clinically significant medical, surgical, psychiatric, or laboratory abnormalities in the judgement of the treating investigator or the EAC
  • Prior/Concomitant Therapy:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2.5 times the upper limit of normal (ULN)
• Significant renal impairment as determined by the following criteria:
  • Creatinine clearance (CrCL) less than or equal to 60 mL/min for subjects \< 65 years of age
  • Creatine clearance (CrCL) greater than or equal to 55 mL/min and the absence of proteinuria or hematuria for subjects ≥ 65 years of age

Age

• Evidence of advanced, age-related macular degeneration (neovascular or geographic atrophy) or intermediate macular degeneration as defined by Beckman classification (Large drusen \> 125 um and/or any AMD pigmentary abnormalities). Evidence of retina/choroid neovascularization from any cause. Evidence of central serous retinopathy.

Other

• Diagnosis/suspicion of secondary or atypical parkinsonism
• High likelihood of needing anti-parkinsonian treatment over the study period, in the opinion of the investigator
• Clinically significant orthostatic hypotension
• Any social or behavioral reason that would preclude completion of the study, in the judgement of the investigator
• Abnormal amylase and/or lipase at screening (may be repeated during screening period)
• Currently lactating, pregnant or planning on becoming pregnant during the study

• Participants who are diagnosed with PD consistent with UK Brain Bank criteria and MDS Research Criteria; must include bradykinesia with sequence effect and motor asymmetry.
• Receiving no anti-parkinsonian therapy
• Modified Hoehn/Yahr Stage \< 3.0
• Montreal Cognitive Assessment ≥ 24
• Patient expected to be able to participate in trial without need for additional anti-parkinsonian therapy
  • Sex and Contraceptive/Barrier Requirements:
• Male participants must agree to practice an acceptable method of highly effective birth control from the screening visit, while on study and for 30 days after receiving the last dose of study drug. Highly effective methods of birth control include sexual abstinence, vasectomy, or a condom with spermicide (men) in combination with their partner's highly effective method.
• Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to either remain abstinent or use adequate and reliable contraception throughout the study and at least 30 days after the last dose of study drug has been taken.
  • Informed Consent:
  • 1\. Capable of giving signed ICF as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
  • Other Inclusions:
  • 1\. Approved as an appropriate and suitable candidate by the EAC.