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

(BeyoND Trial)

Not currently recruiting at 66 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering levodopa/carbidopa, a common treatment for advanced Parkinson's disease. The researchers aim to determine if using a pump to continuously infuse the medication under the skin is safe and effective. This method, known as ND0612, will be assessed for either a 24-hour or 16-hour daily dosing schedule. It suits individuals with advanced Parkinson's who experience at least two hours of "OFF" time (when symptoms return) each day and respond well to morning doses of levodopa. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ND0612, a treatment for Parkinson's disease, is generally safe. In earlier studies, most patients tolerated it well, though some experienced reactions at the administration site. These were the most common side effects, occurring in about 83% of participants in one study. Despite this, the treatment proved safe and effective for managing symptoms over time.

Additionally, long-term research found that ND0612 remained well-tolerated over a year, consistently aiding Parkinson's symptoms. While side effects can occur, current research indicates that ND0612 has a strong safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ND0612 for Parkinson's disease because it offers a unique way to manage symptoms through continuous subcutaneous infusion. Unlike traditional oral treatments that require frequent dosing and can cause fluctuations in symptom control, ND0612 provides a steady delivery of levodopa/carbidopa directly under the skin, which may lead to more consistent blood levels and better management of symptoms. This method could reduce the "off" periods when medication effects wear off, offering patients a smoother day-to-day experience. Additionally, the 24-hour dosing regimen allows for constant symptom control, potentially improving quality of life for those who struggle with nighttime symptoms.

What evidence suggests that ND0612 might be an effective treatment for Parkinson's Disease?

This trial will compare two dosing regimens of ND0612, a continuous under-the-skin infusion of levodopa/carbidopa, to help manage movement issues in people with advanced Parkinson's disease. Studies have shown that ND0612 can provide at least 2 extra hours of "Good" ON-time each day, where patients have better control of their movements without causing troublesome involuntary movements. Research has found the treatment to be safe and well-tolerated over long-term use. ND0612 offers a promising alternative to oral medications for those struggling with inconsistent movement control. ^{2 3 4 5 6}

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.

Cohort 2: Clinically significant ECG rhythm abnormalities.

My condition is diagnosed as atypical or secondary parkinsonism.

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. sciencedirect.com sciencedirect.com/science/article/pii/S1353802025000343

Long-term, continuous, subcutaneous levodopa/carbidopa ... One-year data from the ongoing BeyoND study (NCT02726386) showed that the ND0612 regimen was safe and well tolerated and provided a sustained ≥2-h improvement ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39884033/

3-year outcomes from the open-label BeyoND study One-year data from the ongoing BeyoND study (NCT02726386) showed that the ND0612 regimen was safe and well tolerated and provided a sustained ≥2-h improvement ...

3. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(24)00052-8/abstract

Safety and efficacy of continuous subcutaneous levodopa ... ND0612 might offer a safe and efficacious subcutaneous levodopa infusion approach to managing motor fluctuations in people with Parkinson's ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04006210

Efficacy, Safety and Tolerability Study of ND0612 vs. Oral ... Safety and efficacy of continuous subcutaneous levodopa-carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3 ...

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000202964

Three-Year Data from the Open-Label BeyoND study (PL4. ... One year data showed that ND0612 was safe and well-tolerated and provided a sustained ≥2-hour improvement in daily 'Good' ON-time without troublesome dyskinesia ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38499015/

Safety and efficacy of continuous subcutaneous levodopa ... The most common adverse events were infusion-site reactions (266 [83%] participants during open-label ND0612, and 73 [57%] in the ND0612 group ...