The U.S. Food and Drug Administration (FDA) has given a green light to Titan Pharmaceuticals to begin a first-in-human clinical trial testing an implant that provides continuous release of ropinirole to treat Parkinson’s signs and symptoms.
In the open-label Phase 1/2 trial (NCT03250117), which is now recruiting, roughly 20 Parkinson’s disease patients taking levodopa along with oral ropinirole (marketed as Requip) will be switched to the subdermal, or under the skin, implant for three months. They will continue using levodopa.
This study will measure how much ropinirole is released in the blood during the three months, and evaluate possible side effects caused by the new drug delivery route. It will also look for evidence of treatment efficacy through changes in the severity of Parkinson’s disease in participants. The trial will take place at three or more U.S. sites, although only one — in Michigan — is currently registered.
“New treatments that offer continuous delivery of medication providing non-pulsatile stimulation of dopamine receptors in the brain appear to have some advantages over oral formulations,” Dr. Aaron Ellenbogen of the Michigan Institute of Neurological Disorders said in a press release.
“The ProNeura implants with ropinirole could potentially offer an important treatment option for continuous drug delivery that overcomes the fluctuating drug levels associated with oral administration of ropinirole, and we look forward to conducting this study,” said Ellenbogen, the study’s principal investigator at the site near Detroit.
Requip, a dopaminergic agent, is approved in the U.S. as immediate-release and extended-release tablets to treat such signs and symptoms of Parkinson’s as stiffness, tremors, muscle spasms, and poor muscle control. The immediate release formulation is also approved to treat restless leg syndrome.
But some Parkinson’s patients develop motor complications and dyskinesia, or uncontrolled and jerky movements, after taking oral Requip for several years, due to fluctuations in blood levels of the medication. Dyskinesia can be anything from a slight tremor of the hands to an uncontrollable movement of the upper body or lower limbs.
The implant is based on Titan’s ProNeura technology, and is designed to continuously release a consistent dose of ropinirole for three months or more, avoiding the shifts in blood concentrations when ropinirole is taken as a tablet.
“While oral formulations of ropinirole have greatly benefitted those suffering from Parkinson’s disease, many patients develop serious motor complications and dyskinesias after several years, due to the peak-trough fluctuations of medication in the blood,” said Kate Beebe, PhD, executive vice president and chief development officer at Titan.
“Our ropinirole implant is designed to provide continuous, non-fluctuating therapeutic levels of medication for up to three months, potentially offering patients and clinicians a more effective treatment option,” Beebe said. “We thank the FDA for their timely review and comments on the IND and clinical protocol.”