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

NCT04778176 | Completed Phase 2

• 1 other identifier: TP-0007
• Study Type: interventional
• Target: 17
• Locations: 3 countries
• Sites: 5

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.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (6)

• Variability in plasma concentration of levodopa as assessed with the Levodopa Fluctuation Index (Cmax-Cmin)/Caverage)

  Comparing Day 2 to Day 1 in steady state (4-12 hours). Fluctuation index will also be calculated by the hour.

  pre-dose and every 30 minutes for 12 hours on Days 1 and 2.

• Treatment Emergent Adverse Events

  Screening to Day 29

• Serious Adverse Events

  Screening to Day 29

• Treatment Emergent Adverse Events leading to discontinuation

  Screening to Day 29

• Percent of participants that complete study

  Screening to Day 29

• Difference in OFF time between Days 1 and 15, based on in-person investigator ratings

  Investigator-rated assessment of motor state (ON or OFF) pre-dose and every 30 minutes for 12 hours.

  Day 1 compared to Day 15

Secondary Outcomes (12)

• Coefficient of variation (CV) for plasma levodopa.

  pre-dose and every 30 minutes for 12 hours on Days 1 and 2.

• Variability in plasma concentration of levodopa as assessed with the Levodopa Fluctuation Index (Cmax-Cmin)/Caverage).

  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.

• Levodopa and Carbidopa peak plasma concentration (Cmax)

  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.

• Variability in plasma levodopa comparing Dopafuse and oral levodopa tablets based on fluctuation index and CV in participants who are H. pylori negative/positive

  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.

• Questionnaire for Impulse Control Disorders in Parkinson's Disease Rating Scale (QUIP-RS)

  Screening to Day 29

Other Outcomes (1)

• A comparison of the subgroups who are H. pylori positive and negative will be performed as an exploratory analysis.

  Screening to Day 15

Study Arms (1)

DopaFuse Delivery System 50mg LD/hr or 68mg LD/hr flow rate

EXPERIMENTAL

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

Interventions

continuous oral delivery of levodopa/carbidopa COMBINATION_PRODUCT

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.

DopaFuse Delivery System 50mg LD/hr or 68mg LD/hr flow rate

Eligibility Criteria

• Age: 30 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Parkinson's Disease consistent with UK Brain Bank Criteria
• Age at least 30 years old at time of consent
• 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)
• Suitable for oral retainer wear
• A good response to Levodopa, as assessed by the Investigator
• At least 2 hours of wearing OFF time per day, as reported by the participant
• Predictable early morning OFF periods, in the judgement of the participant and the Investigator
• 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.
• A modified Hoehn and Yahr of ≤ 3 in the ON state at screening
• A stable regimen of anti-PD medications for the last 28 days prior to Screening
• A Mini-Mental State Examination (MMSE) Score ≥26
• Capable of giving signed informed consent
• Approved for entry into the study by the Enrollment Authorization Committee (EAC)

You may not qualify if:

• Atypical or secondary Parkinson's Disease
• Severe Dyskinesia that might interfere with study performance in the judgement of Investigator
• Clinically significant dysphagia or sialorrhea that might interfere with administration of study intervention in the judgement of the Investigator
• Use of extended release levodopa within 28 days prior to screening
• 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.
• Presence of clinically significant orthostatic hypotension at screening, in the opinion of Investigator or the EAC
• 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.
• History of psychosis or hallucinations in the past six months
• Any malignancy in the past 5 years (excluding basal cell carcinoma of the skin or cervical carcinoma in situ that have been successfully treated.)
• Current or previous diagnosis of malignant melanoma or the presence of any suspicious skin lesion based on physical exam findings
• Unable to give blood required for the study
• History of allergic reaction to plastics
• LD infusion therapy (i.e. Duodopa); current or previous continuous apomorphine infusion treatment.
• Participation in any other clinical trial \<30 days prior to screening visit.
• Presence of two third molars ("wisdom teeth") on the upper dentition

Sponsors & Collaborators

• SynAgile Corporation: lead
• Clintrex Research Corporation: collaborator
• TFS Trial Form Support: collaborator
• Clinical Data Science GmbH: collaborator

Study Sites (5)

San Raffaele Cassino

Cassino, 03043, Italy

Location

Centro Parkinson, Policlinico Tor Vergata

Rome, 00133, Italy

Location

IRCCS San Raffaele Pisana

Rome, 00163, Italy

Location

Centre Hospitalier de Luxembourg

Luxembourg, Luxembourg

Location

Neuroscience Centre (CINAC)

Móstoles, 28938, Spain

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Carbidopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Methyldopa; Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Hydrazines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Ephraim Heller, MBA

  SynAgile Corporation

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: March 2, 2021
• Study Start: June 16, 2021
• Primary Completion: July 21, 2022
• Study Completion: August 2, 2022
• Last Updated: August 10, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3); LU (1); ES (1)