Clinical Trial of Intranasal Delivery of NT-301

Exclusion Criteria

• •1. Any significant medical condition, physical or psychiatric illness or history of depression that could, in the Investigator's (or qualified designee) opinion, compromise the participant's safety or interfere with the completion of this study.
• •2. History of clinically significant CNS, cardiac, pulmonary, metabolic, renal, hepatic, or gastrointestinal (GI) conditions including gastric bypass or other weight loss surgical procedure.
• •3. Any condition including the presence of laboratory abnormalities, which according to the Investigator (or qualified designee), places the participant at unacceptable risk if they were to participate in the study or may confound the ability to interpret data from the study. This includes the presence of uncontrolled current illness (e.g., an infection), a viral infection, seasonal allergy, or concurrent skin rash.
• •4. Any nasal condition, including nasal congestion, physical blockage of either nostril, deviated septum, structural or anatomical nasal conditions or nasal surgery in the last 6 months. Use of topical nasal medications (e.g., acute or chronic use of prescription or over the counter nasal sprays) that may affect the administration or absorption of the study drug.
• •5. Use of 5HT3 antagonists, drugs known to prolong QTc, and use of antihypertensives.
• •6. The participant has a medical history of or a positive blood test for human immunodeficiency virus (HIV: HIV, anti-HIV1 and anti-HIV2 antibodies), hepatitis C virus (HCV, anti-HCV antibodies), or hepatitis B surface antigen (HBsAg) at screening.
• •7. Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), serum creatine, or total bilirubin \>1.5x the upper limit of normal (ULN). These laboratory tests may be repeated once if they are abnormal on first screening, and if there is a medical reason to believe the results may be inaccurate. If the repeat test is within the normal range, the participant may be included in the study only if the Investigator (or qualified designee) considers that the previous finding will not compromise the participant's safety and will not interfere with the interpretation of safety data.
• •8. A positive drug or alcohol screen. A positive drug or alcohol screen test result may be verified by re-testing at the discretion of the Investigator (or qualified designee), with up to 1 false positive result permitted.
• •9. History of regular alcohol consumption within 6 months of screening defined as an average weekly intake of \>21 units. One unit is equivalent to 10 g of alcohol and the following can be used as a guide: a half-pint (\~240 mL) of beer, 1 glass (125 mL) of wine or 1 (30 mL) measure of spirits.
• •10. The participant is unwilling to abstain from alcohol consumption from 24 h prior to treatment with any study intervention (including domperidone) and until discharge from the CRU, and for 24 h prior to all other outpatient visits to the CRU.
• •11. The participant is pregnant or planning to become pregnant within 90 days of the study or is breastfeeding.
• •12. Major surgery within 4 weeks of screening that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the participant in the opinion of the Investigator (or qualified designee).
• •13. Use of tobacco or nicotine products exceeding 5 cigarettes (or equivalent) per week in any form within 30 days prior to treatment with any study intervention (including domperidone), or unwillingness to refrain from smoking, vaping, or using any nicotine products for at least 48 h prior to dosing with any study intervention (including domperidone), the confinement period, and any follow up visits.
• •14. The participant uses or is planning to use any prescription or non-prescription medications (with the exception of hormonal contraceptives), herbal and dietary supplements, within 5 days or 5 half-lives (whichever is longer) prior to treatment with any study intervention (including domperidone), unless in the opinion of the PI, local MM and Sponsor medical representative, the medication is not expected to interfere with the study procedures or compromise participant safety
• •15. Participation in a clinical trial and receipt of an investigational medication within 90 days, 5 half-lives (if known) or twice the duration of the biological effect of any medication, whichever is longer, prior to the first dose of study intervention.
• •16. Use of any strong CYP450-3A4/5 inhibiting or inducing agents within 14 days of dosing with any study intervention (including domperidone) and for the duration of the study.
• •17. Consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges, within 14 days prior to dosing with any study intervention (including domperidone) and participant is unwilling to abstain from consumption of these products until after discharge from the CRU.
• •18. Participant is unwilling to abstain from the consumption of caffeine and/or xanthine containing products (e.g., coffee, tea, chocolate, and caffeine containing sodas, etc.) from time of admission to the CRU on Day -1 until after discharge from the CRU.
• •19. Known sensitivity to any study intervention, including NT-301, apomorphine HCl and domperidone.
• •20. Loss or donation of whole blood (\>499 mL) within 3 months and/or plasma donation within 2 weeks, prior to dosing with any study intervention (including domperidone), or intention to donate blood or blood products during the study.
• •21. The participant has a history of cancer, with the exception of basal cell carcinoma or in situ cervical cancer that has been in remission for ≥5 years prior to first dose of study treatment.
• •22. Participants with a pre-disposition to nausea and vomiting (e.g., history of severe travel sickness).
• •23. The participant is unwilling or unable to follow protocol requirements, including domperidone self-administration and diary completion, and attendance at follow up visit(s), or otherwise unsuitable for study participation in the opinion of the Investigator.