Assessing the Pharmacokinetics, Safety, Tolerability and Efficacy of Continuous Oral Levodopa Via the DopaFuse® Delivery System in Parkinson's Disease Patients
Assessing the Pharmacokinetics, Safety, Tolerability and Efficacy of Continuous Oral Levodopa Via the DopaFuse® Delivery System in Parkinson's Disease Patients
The purpose of this study is to evaluate whether the DopaFuse System can reduce the
 fluctuation of plasma levodopa levels compared to participants' standard intermittent doses
 of oral LD/CD tablets (background treatment). It will also assess whether the system is safe,
 well tolerated, and can relieve motor symptoms.
Inclusion Criteria:

 1. Diagnosis of Parkinson's Disease consistent with UK Brain Bank Criteria

 2. Age at least 30 years old at time of consent

 3. Male and Female participants (Women of child-bearing potential (WOCB) are eligible for
 participation if they are not pregnant or breastfeeding and agree to follow the
 contraceptive guidance in Appendix 3 during the treatment period and for at least 30
 days after the last dose of study treatment)

 4. Suitable for oral retainer wear

 5. A good response to Levodopa, as assessed by the Investigator

 6. At least 2 hours of wearing OFF time per day, as reported by the participant

 7. Predictable early morning OFF periods, in the judgement of the participant and the
 Investigator

 8. Taking 400-1,200 mg of LD/CD per day in at least 4 doses, with stable dosing for the
 last 28 days prior to screening.

 9. A modified Hoehn and Yahr of ≤ 3 in the ON state at screening

 10. A stable regimen of anti-PD medications for the last 28 days prior to Screening

 11. A Mini-Mental State Examination (MMSE) Score ≥26

 12. Capable of giving signed informed consent

 13. Approved for entry into the study by the Enrollment Authorization Committee (EAC)

 Exclusion Criteria:

 1. Atypical or secondary Parkinson's Disease

 2. Severe Dyskinesia that might interfere with study performance in the judgement of
 Investigator

 3. Clinically significant dysphagia or sialorrhea that might interfere with
 administration of study intervention in the judgement of the Investigator

 4. Use of extended release levodopa within 28 days prior to screening

 5. Any clinically significant medical, surgical, or psychiatric condition; laboratory
 value or ECG result which, in the opinion of the Investigator, makes the participant
 unsuitable for study entry or potentially unable to complete all aspects of the study.

 6. Presence of clinically significant orthostatic hypotension at screening, in the
 opinion of Investigator or the EAC

 7. Suicidal ideation within 1 year prior to the Screening Visit as evidenced by answering
 "yes" to Questions 4 or 5 on the suicidal ideation portion of the Columbia Suicide
 Severity Rating Scale (C-SSRS) or attempted suicide within the last 5 years.

 8. History of psychosis or hallucinations in the past six months

 9. Any malignancy in the past 5 years (excluding basal cell carcinoma of the skin or
 cervical carcinoma in situ that have been successfully treated.)

 10. Current or previous diagnosis of malignant melanoma or the presence of any suspicious
 skin lesion based on physical exam findings

 11. Unable to give blood required for the study

 12. History of allergic reaction to plastics

 13. LD infusion therapy (i.e. Duodopa); current or previous continuous apomorphine
 infusion treatment.

 14. Participation in any other clinical trial <30 days prior to screening visit.

 15. Presence of two third molars ("wisdom teeth") on the upper dentition

 16. Participants who, for any reason, are judged by the Investigator or the EAC to be
 inappropriate for this study, including participants who are unable to communicate or
 cooperate with the Investigator or who have/had a clinically significant illness or
 abnormal physical examination that may compromise safety of the participant during the
 trial or affect ability of the participant to adhere to study procedures.

 17. Participants taking non-selective monoamine oxidase (MAO) inhibitors

 18. Participants with known hypersensitivity to the active ingredients (levodopa,
 carbidopa) or excipients (Benzoic Acid, Disodium Edetate, Medium Chain Triglycerides,
 Poloxamer 188) of the drug paste

 19. Participants with narrow-angle glaucoma