Continuous Subcutaneous Infusion of Levodopa/Carbidopa for Parkinson's Disease

(BeyoND Trial)

Recruiting at 56 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: NeuroDerm Ltd.

Must be taking: Levodopa, Carbidopa

Must not be taking: Apomorphine

Disqualifiers: Atypical parkinsonism, Acute psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 months

214 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a pump that delivers medication under the skin for patients with advanced Parkinson's Disease. The treatment aims to improve movement symptoms by increasing dopamine levels in the brain. This method has been used for many years to manage motor complications in advanced Parkinson's Disease.

Will I have to stop taking my current medications?

The trial requires that participants be stable on their Parkinson's medications for at least 30 days before starting. However, continuous apomorphine treatment must be stopped at least 4 weeks before the screening visit and is not allowed during the trial.

Is continuous subcutaneous infusion of levodopa/carbidopa (ND0612) safe for humans?

Studies on ND0612, a continuous subcutaneous infusion of levodopa/carbidopa for Parkinson's disease, show it is generally safe in humans. A study in minipigs found no systemic adverse effects, and while there were some local skin reactions at infusion sites, these were not considered harmful and showed signs of recovery. ^{1 2 3 4 5}

How is the drug ND0612 different from other Parkinson's disease treatments?

ND0612 is unique because it delivers levodopa/carbidopa continuously through a subcutaneous (under the skin) infusion, which avoids the need for invasive surgery and helps maintain stable drug levels, reducing motor fluctuations in Parkinson's disease patients. ^{1 2 3 6 7}

What data supports the effectiveness of the drug ND0612 for Parkinson's disease?

Research shows that ND0612, a continuous subcutaneous infusion of levodopa/carbidopa, helps stabilize levodopa levels in the blood, which can reduce motor fluctuations in Parkinson's disease patients. This method is less invasive than other infusion systems and may offer a more convenient treatment option for those not well controlled on oral medication. ^{1 2 3 7 8}

Who Is on the Research Team?

Laurence Salin, MD

Principal Investigator

NeuroDerm Ltd.

Are You a Good Fit for This Trial?

This trial is for adults over 30 with advanced Parkinson's Disease who are stable on their current medications, have a mental state score above 26, and can self-administer or get help with the infusion. They need to experience at least 2 hours of 'OFF' time daily and respond well to Levodopa. People with recent drug abuse history, significant heart rhythm problems, liver or kidney issues affecting drug metabolism, psychosis in the past six months, certain other medical conditions or treatments for PD like neurosurgery aren't eligible.

Inclusion Criteria

I am on Parkinson's medication and have tried at least one other treatment for over 30 days.

Cohort 2: No clinically significant medical, psychiatric or laboratory abnormalities which the investigator judges would be unsafe or non-compliant in the study.

Cohort 1: Subject is able to, and has signed an Institutional Review Board/Ethics Committee (IRB/EC)-approved informed consent form (ICF).

Exclusion Criteria

Cohort 2: Acute psychosis or hallucinations in past 6 months.

My condition is diagnosed as atypical or secondary parkinsonism.

Cohort 2: Clinically significant ECG rhythm abnormalities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ND0612 via a continuous subcutaneous infusion pump system, with home visits and monthly in-clinic visits for safety and efficacy assessments

12 months

1 home visit in the first week, monthly in-clinic visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

3 visits (in-person)

Optional Treatment Extension

Participants may continue treatment for up to 102 months with quarterly clinic visits to assess long-term safety

Up to 102 months

Quarterly in-clinic visits

What Are the Treatments Tested in This Trial?

Interventions

• ND0612

Trial Overview The study tests ND0612—a levodopa/carbidopa solution given through a pump as a continuous subcutaneous (under the skin) infusion—to see if it's safe long-term for those with advanced Parkinson's Disease. It’s an open-label international trial where everyone knows they're getting this treatment.

How Is the Trial Designed?

Group I: 24-hour dosing regimen Experimental Treatment 1 Intervention

Continuous SC infusion over 24 hours: fixed day rate of up to 0.64 mL/h for 18 hours, followed by a night rate of 0.08 mL/h for 6 hours to deliver a total daily dose of up to 720/90 mg of levodopa/carbidopa. All patients who had been previously assigned to the 24-hour group in the prior study continued on this dosing regimen; patients who had previously been assigned to the 14-hour daytime regimen were switched to the 24-hour regimen.

Group II: 16-hour dosing regimen Experimental Treatment 1 Intervention

Continuous SC infusion for over 16 hours: fixed rate of 0.75 mL/h to deliver a total infusion dose of 720/90 mg of levodopa/carbidopa over 16 hours. The device is removed at night and patients in this group also receive a morning oral dose of levodopa/carbidopa upon awakening.

Who Is Running the Clinical Trial?

NeuroDerm Ltd.

Lead Sponsor

Trials

14

Recruited

840+

Published Research Related to This Trial

Chronic low-dose levodopa-carbidopa therapy in 92 Japanese patients with Parkinson's disease showed satisfactory benefits in managing motor disabilities and improving quality of life over an average treatment duration of 6.2 years, with a mean daily dose of 186.4 mg.

The therapy resulted in a low incidence of adverse events, with motor fluctuations at 8.7%, dyskinesias at 6.5%, and hallucinations at 14.1%, indicating that low-dose treatment can be effective and safe when combined with small amounts of dopamine agonists and amantadine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study. Kitagawa, M., Tashiro, K.[2019]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Continuous Subcutaneous Levodopa Delivery for Parkinson's Disease: A Randomized Study. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The pharmacokinetics of continuous subcutaneous levodopa/carbidopa infusion: Findings from the ND0612 clinical development program. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Subcutaneous Levodopa Infusion for Parkinson's Disease: 1-Year Data from the Open-Label BeyoND Study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Foslevodopa/Foscarbidopa: A New Subcutaneous Treatment for Parkinson's Disease. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Subcutaneous lisuride infusion in Parkinson's disease. Response to chronic administration in 34 patients. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Ninety-day Local Tolerability and Toxicity Study of ND0612, a Novel Formulation of Levodopa/Carbidopa, Administered by Subcutaneous Continuous Infusion in Minipigs. [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

Low-dose levodopa therapy in Japanese patients with Parkinson's disease: a retrospective study. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Levodopa-Carbidopa Intestinal Gel Monotherapy: GLORIA Registry Demographics, Efficacy, and Safety. [2020]