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

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ClinicalTrials.gov Identifier: NCT04778176
Recruitment Status : Recruiting
First Posted : March 2, 2021
Last Update Posted : July 27, 2021
Sponsor:
Collaborators:
Clintrex Research Corporation
TFS Trial Form Support
Clinical Data Science GmbH
Information provided by (Responsible Party):
SynAgile Corporation

Tracking Information
First Submitted Date  ICMJE February 22, 2021
First Posted Date  ICMJE March 2, 2021
Last Update Posted Date July 27, 2021
Actual Study Start Date  ICMJE June 16, 2021
Estimated Primary Completion Date December 14, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 26, 2021)
  • 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.
  • Treatment Emergent Adverse Events [ Time Frame: Screening to Day 29 ]
  • Serious Adverse Events [ Time Frame: Screening to Day 29 ]
  • Treatment Emergent Adverse Events leading to discontinuation [ Time Frame: Screening to Day 29 ]
  • Percent of participants that complete study [ Time Frame: Screening to Day 29 ]
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 26, 2021)
  • 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.
  • 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.
  • 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. ]
  • 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. ]
  • Questionnaire for Impulse Control Disorders in Parkinson's Disease Rating Scale (QUIP-RS) [ Time Frame: Screening to Day 29 ]
  • Columbia - Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Screening to Day 29 ]
  • 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.
  • 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.
  • 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.
  • 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 ]
  • 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. ]
  • 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. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 26, 2021)
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 ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Assessing the Pharmacokinetics, Safety, Tolerability and Efficacy of Continuous Oral Levodopa Via the DopaFuse® Delivery System in Parkinson's Disease Patients
Official Title  ICMJE Assessing the Pharmacokinetics, Safety, Tolerability and Efficacy of Continuous Oral Levodopa Via the DopaFuse® Delivery System in Parkinson's Disease Patients
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Parkinson's Disease
Intervention  ICMJE 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.
Study Arms  ICMJE 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).
Intervention: Combination Product: continuous oral delivery of levodopa/carbidopa
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 26, 2021)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 28, 2021
Estimated Primary Completion Date December 14, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ephraim Heller, MBA +1 510-788-4435 Clinical@synagile.com
Listed Location Countries  ICMJE Italy,   Luxembourg
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04778176
Other Study ID Numbers  ICMJE TP-0007
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party SynAgile Corporation
Study Sponsor  ICMJE SynAgile Corporation
Collaborators  ICMJE
  • Clintrex Research Corporation
  • TFS Trial Form Support
  • Clinical Data Science GmbH
Investigators  ICMJE
Study Chair: Ephraim Heller, MBA SynAgile Corporation
PRS Account SynAgile Corporation
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP