Phase 2 Clinical Trial

SynAgile is currently conducting a Phase 2 clinical trial on the DopaFuse Delivery System titled “Study of Continuous Oral Levodopa” (SCOL) in order to study the safety and efficacy of DopaFuse. The SCOL study is enrolling 24 patients in Italy, Luxembourg and Spain beginning in June of 2021.

The purpose of this study is to evaluate whether the DopaFuse System can reduce the fluctuation of plasma levodopa levels as compared to participants’ standard intermittent doses of oral LD/CD tablets. It will also assess whether the system is safe, well tolerated, and can relieve motor symptoms.

Over the 15-day active period of the trial, each participant will receive DopaFuse treatment for three days under inpatient observation and 11 days via in-home use. On Day 1, participants will take their usual oral immediate release LD/CD tablets. On Day 2, participants will receive DopaFuse alone. Days 3-15 will involve participants taking their usual initial AM dose of LD/CD, followed by continuous DopaFuse for the rest of the day.

More details can be found here.

Human Factors Formative Study

In 2018-2019, a formative human factors (HF) study was conducted to investigate if the DopaFuse Delivery System could be used safely and effectively by its intended users (i.e., patients with Parkinson’s disease and their caregivers) in the intended use environments of a Phase 2 clinical trial. A simulated-use HF study was conducted on patients with Parkinson’s disease and their caregivers. During the study, there was no drug paste inside the container, and the retainer was placed in a dental manikin by both the patients and the caregivers. Patients ranged from age 65 to 89 years and the caregivers from age 52 to 72 years. Each pair was trained on the system during a session lasting 45 minutes then, following 1 hour of memory decay, were first tested individually in a first-time use scenario. In a final session, both the patient and caregiver were tested together.

Participants were tested on their ability to conduct the identified critical task of inserting the container properly into the retainer as well as a number of noncritical tasks. The critical task was evaluated by two study assessments; one was conducted by observing participants’ performance while the second was presented as a knowledge task question. Overall, the study showed that all patient-participant pairs successfully completed the critical task of properly inserting the container into the retainer pocket. It was concluded that DopaFuse could be used safely and effectively by its intended users during a Phase 2 clinical trial.

Proof of Concept Study

A SynAgile-sponsored proof of concept study tested the hypothesis that continuous administration of a LD/CD dispersion into the mouth would have superior pharmacokinetics and efficacy versus standard therapy with intermittent pills.

Study Abstract

Objective: To compare pharmacokinetics and efficacy of intermittent versus continuous oral delivery of levodopa/carbidopa (LD/CD) in Parkinson Disease (PD) patients complicated by motor fluctuations.

Methods: 18 PD patients with wearing off episodes were enrolled in an open label study. Pharmacokinetic and efficacy measures were assessed comparing treatment with standard intermittent oral levodopa and “continuous” oral levodopa. For purpose of this study continuous was defined as sips of a levodopa dispersion administered at 5-10 minute intervals. On Day 1 patients received their regular oral LD/CD dose. On Day 2 patients received the same total LD/CD dose via “continuous” oral administration. On Day 3 patients received their regular LD/CD morning dose followed by “continuous” administration of LD/CD. The total daily LD/CD dose was the same on each day of the study.

Results: There was significantly less variability in plasma LD concentration with “continuous” versus intermittent oral levodopa treatment (fluctuation index was 0.99+/-0.09 vs 1.38+/-0.12 (p < 0.001) and coefficient of variation was 0.35+/-0.03 vs 0.49+/-0.04 to (p < 0.001)). The mean OFF time was decreased by 43% (p < 0.001) with “continuous” oral levodopa therapy. No treatment-related safety or tolerability issues were observed.

Representative plasma levodopa levels following administration of standard intermittent oral (red) and continuous oral (blue) LD/CD in a single PD individual. Note that continuous oral delivery avoids the marked fluctuations and the periodic low trough levels associated with intermittent oral delivery.

Conclusions: “Continuous” oral LD/CD therapy was associated with less plasma variability and reduced off time in comparison to standard intermittent oral LD/CD therapy. Double blind trials are planned.

Trial Registration: clinical - NCT02763137

For more details, please view the publication here.