Phase 2 Trial Supports DopaFuse for Levodopa-carbidopa Oral Delivery

Continuous delivery system found to ease motor complications in Parkinson's

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by Andrea Lobo |

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Several graphs and a pill bottle are used to illustrate the results of clinical trials in medicine.

Treatment with DopaFuse, a continuous oral levodopa-carbidopa delivery system being developed by SynAgile, was safe and lessened motor complications in people with Parkinson’s disease, according to results from a Phase 2 clinical trial.

“These results suggest that the DopaFuse [levodopa-carbidopa] delivery system can provide a safe, non-invasive treatment for motor complications without the need for a surgical procedure,” Warren Olanow, professor emeritus at the Mount Sinai School of Medicine, in New York, said in a press release.

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Testing the DopaFuse delivery system

Parkinson’s is characterized by the death and dysfunction of dopaminergic neurons, or nerve cells that communicate by releasing a signaling molecule, or neurotransmitter, called dopamine.

Levodopa is one of the main medications used to treat Parkinson’s motor symptoms, such as stiffness and slowness of movement. In the brain, it is converted into dopamine, which helps to ease the symptoms of the neurodegenerative disease.

This treatment usually is given in combination with medications such as carbidopa to avoid the breakdown of levodopa outside the brain.

The response to levodopa therapy is usually robust at first, but patients tend to develop motor fluctuations as the disease progresses. This results in periods when symptoms are adequately controlled — known as “on” time — and periods of emergent Parkinson’s symptoms, called “off” time, when the medication wears off, due to a reduction in the duration of its benefits.

Given this, a therapeutic alternative that could maintain constant levels of levodopa in the plasma would be a major advance for controlling motor symptoms and reducing the “on-off” effect.

“Motor complications can have a profoundly negative impact on the lives of Parkinson’s disease patients. A safe, convenient, noninvasive, continuous oral levodopa therapy would be a major advance in treatment,” said Olanow, also the CEO of Clintrex Research, one of the collaborators in this study.

The new DopaFuse system consists of a custom-made, and discrete, tooth-attached retainer, with a small medication container that continuously releases levodopa/carbidopa into the back of the mouth. The medication is swallowed with saliva and absorbed via the gastrointestinal route.

The system is easily removed to replace the container, and for eating and teeth brushing. It does not interfere with speech, swallowing, or drinking.

To test it in patients, SynAgile conducted a Phase 2 trial (NCT04778176) that involved 16 people with Parkinson’s disease at several medical institutions.

Along with Clintrex, TFS Trial Form Support and Clinical Data Science GmbH collaborated on the study.

These results suggest that the DopaFuse [levodopa-carbidopa] delivery system can provide a safe, non-invasive treatment for motor complications without the need for a surgical procedure

Over 14 days (two weeks), treatment with standard intermittent oral levodopa-carbidopa tablets was compared with the continuous delivery of the medications using the DopaFuse system.

During the study, the variability in plasma levodopa levels was significantly reduced with levodopa-carbidopa DopaFuse delivery, compared with the oral treatment.

The continuous delivery of the medications using DopaFuse also was found to significantly reduce off time and improve on time without severe dyskinesia — the uncontrolled and involuntary movements that are frequently a consequence of long-term use of levodopa.

Activities of daily living, as measured by the Unified Parkinson’s Disease Rating Scale (UPDSR) Part II, significantly improved with the use of DopaFuse, compared with oral tablets.

Patients had no serious or clinically significant adverse events, and the oral reactions reported were mild and transient. According to SynAgile, patients reportedly were highly satisfied with the DopaFuse system.

“SynAgile is now scaling up manufacturing at its facility in San Jose, CA, in preparation for a double-blind Phase 3 clinical trial of the DopaFuse system,” said Ephraim Heller, CEO of SynAgile.

In a double-blind trial, neither participants nor researchers know who is receiving the therapy and who is getting the placebo.

Further details on that trial are not yet available.