Assessing the Pharmacokinetics, Safety, Tolerability and Efficacy of Continuous Oral Levodopa Via the DopaFuse® Delivery System in Parkinson's Disease Patients (SCOL)

• ClinicalTrials.gov Identifier: NCT04778176
• Recruitment Status: Completed
• First Posted: March 2, 2021
• Last Update Posted: August 10, 2022
• Sponsor: SynAgile Corporation
• Collaborators: Clintrex Research Corporation; TFS Trial Form Support; Clinical Data Science GmbH
• Information provided by (Responsible Party): SynAgile Corporation

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Combination Product: continuous oral delivery of levodopa/carbidopa	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessing the Pharmacokinetics, Safety, Tolerability and Efficacy of Continuous Oral Levodopa Via the DopaFuse® Delivery System in Parkinson's Disease Patients
• Actual Study Start Date: June 16, 2021
• Actual Primary Completion Date: July 21, 2022
• Actual Study Completion Date: August 2, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: DopaFuse Delivery System 50mg LD/hr or 68mg LD/hr flow rate; Either 50mg/13mg LD/CD per hour or 68mg/17mg LD/CD per hour flow rate based upon Subject's standard levodopa (LD) dose. Subjects will routinely wear each container for approximately 5 hours (3 containers per day).	Combination Product: continuous oral delivery of levodopa/carbidopa; The system consists of a reusable custom dental retainer, its case, and a pre-filled, single-use container which continuously releases levodopa/carbidopa into the back of the mouth.

Outcome Measures

Primary Outcome Measures :

1. Variability in plasma concentration of levodopa as assessed with the Levodopa Fluctuation Index (Cmax-Cmin)/Caverage) [ Time Frame: pre-dose and every 30 minutes for 12 hours on Days 1 and 2. ]
   Comparing Day 2 to Day 1 in steady state (4-12 hours). Fluctuation index will also be calculated by the hour.
2. Treatment Emergent Adverse Events [ Time Frame: Screening to Day 29 ]
3. Serious Adverse Events [ Time Frame: Screening to Day 29 ]
4. Treatment Emergent Adverse Events leading to discontinuation [ Time Frame: Screening to Day 29 ]
5. Percent of participants that complete study [ Time Frame: Screening to Day 29 ]
6. Difference in OFF time between Days 1 and 15, based on in-person investigator ratings [ Time Frame: Day 1 compared to Day 15 ]
   Investigator-rated assessment of motor state (ON or OFF) pre-dose and every 30 minutes for 12 hours.

Secondary Outcome Measures :

1. Coefficient of variation (CV) for plasma levodopa. [ Time Frame: pre-dose and every 30 minutes for 12 hours on Days 1 and 2. ]
   This will be calculated between 4 and 12 hours on Days 1 and 2 comparing DopaFuse and oral levodopa tablets.
2. Variability in plasma concentration of levodopa as assessed with the Levodopa Fluctuation Index (Cmax-Cmin)/Caverage). [ Time Frame: pre-dose and every 30 minutes for 12 hours on Days 1 and 2. Pre-dose and at 30 minute intervals for two hours, and at one-hour intervals for the remainder of the 12 hours on Day 3. ]
   Comparing Day 3 to Day 1, as well as Day 2 (0-12 hours) to Day 1. Fluctuation index will also be calculated by the hour.
3. Levodopa and Carbidopa peak plasma concentration (Cmax) [ Time Frame: pre-dose and every 30 minutes for 12 hours on Days 1 and 2. Pre-dose and at 30 minute intervals for two hours, and at one-hour intervals for the remainder of the 12 hours on Day 3. ]
4. Variability in plasma levodopa comparing Dopafuse and oral levodopa tablets based on fluctuation index and CV in participants who are H. pylori negative/positive [ Time Frame: pre-dose and every 30 minutes for 12 hours on Days 1 and 2. Pre-dose and at 30 minute intervals for two hours, and at one-hour intervals for the remainder of the 12 hours on Day 3. ]
5. Questionnaire for Impulse Control Disorders in Parkinson's Disease Rating Scale (QUIP-RS) [ Time Frame: Screening to Day 29 ]
6. Columbia - Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Screening to Day 29 ]
7. Difference in OFF Time between Day 1 and Day 3 [ Time Frame: Day 1 and Day 3 ]
   Investigator-rated assessment of motor state (ON or OFF) pre-dose and every 30 minutes for 12 hours.
8. Difference in ON Time without troublesome dyskinesia between Days 1, 3 and 15 [ Time Frame: Days 1, 3, and 15 ]
   Investigator-rated assessment of motor state (ON or OFF) pre-dose and every 30 minutes for 12 hours.
9. Difference in ON Time with troublesome (severe) dyskinesia between Days 1, 3 and 15 [ Time Frame: Days 1, 3 and 15 ]
   Investigator-rated assessment of motor state (ON or OFF) pre-dose and every 30 minutes for 12 hours.
10. Change in Unified Parkinson's Disease Rating Scale Part III at 6 hours after morning dose between Days 1, 3 and 15 [ Time Frame: Days 1, 3 and 15 ]
11. Levodopa and Carbidopa time to maximum plasma concentration (Tmax) [ Time Frame: pre-dose and every 30 minutes for 12 hours on Days 1 and 2. Pre-dose and at 30 minute intervals for two hours, and at one-hour intervals for the remainder of the 12 hours on Day 3. ]
12. Levodopa and Carbidopa area under the plasma concentration versus time curve (AUC) [ Time Frame: pre-dose and every 30 minutes for 12 hours on Days 1 and 2. Pre-dose and at 30 minute intervals for two hours, and at one-hour intervals for the remainder of the 12 hours on Day 3. ]

Other Outcome Measures:

1. A comparison of the subgroups who are H. pylori positive and negative will be performed as an exploratory analysis. [ Time Frame: Screening to Day 15 ]

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Italy

San Raffaele Cassino

Cassino, Italy, 03043

Centro Parkinson, Policlinico Tor Vergata

Rome, Italy, 00133

IRCCS San Raffaele Pisana

Rome, Italy, 00163

Luxembourg

Centre Hospitalier de Luxembourg

Luxembourg, Luxembourg

Spain

Neuroscience Centre (CINAC)

Móstoles, Spain, 28938

Sponsors and Collaborators

SynAgile Corporation

Clintrex Research Corporation

TFS Trial Form Support

Clinical Data Science GmbH

Investigators

• Study Chair: Ephraim Heller, MBA; SynAgile Corporation

More Information

• Responsible Party: SynAgile Corporation
• ClinicalTrials.gov Identifier: NCT04778176
• Other Study ID Numbers: TP-0007
• First Posted: March 2, 2021
• Last Update Posted: August 10, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Levodopa; Carbidopa; Antiparkinson Agents; Anti-Dyskinesia Agents; Dopamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Aromatic Amino Acid Decarboxylase Inhibitors; Enzyme Inhibitors