A new extended-release formulation of carbidopa-levodopa called IPX066 (Rytary®) is safe and effective in treating the symptoms of early-stage Parkinson’s disease (PD), according to the results of a rigorous Phase III clinical trial. The research appears in the September 5 online issue of Parkinsonism and Related Disorders.
Carbidopa-levodopa, usually taken as Sinemet®, is the gold standard therapy for the movement symptoms of PD. But over time, many people develop “fluctuations,” when during a surge of the medication after a dose is taken, a person will experience dyskinesia, and then when levels decrease there is “wearing off,” or worsening PD symptoms. Despite other medication options to steady levodopa’s effects – controlled-release formulation of Sinemet®, dopamine agonists, or medications that slow down the breakdown of levodopa – fluctuations are still a major motor complication of PD.
An experimental formulation of carbidopa-levodopa known as IPX066 addresses this problem. Some of the beads in the capsule are released quickly and others dissolve at various rates. Researchers at several institutions, led by Kelly E. Lyons, Ph.D., at the University of Kansas Medical Center, tested the drug’s safety and effectiveness in the most rigorous type of clinical trial: randomized, double-blind, and placebo-controlled.
The researchers recruited 381 study participants in the US and Europe who were living with early to moderate Parkinson’s who had not taken levodopa for at least four weeks before enrollment. In addition, to be included in the study, participants had to have scores on the UPDRS parts II and III, a standard rating scale of symptoms, totaling 18 or higher. On average, participants were about 65 years old, and about 55 percent were men. The researchers divided participants into four groups, each receiving a pill three times a day, for 30 weeks: either a placebo (a pill that looked like the medication) or 145 mg, 245 mg or 390 mg of levodopa as IPX066.
- At all three doses, participants experiencing IPX066 experienced improvement in PD movement symptoms comparable to improvements seen in people taking Sinemet® for the first time after PD diagnosis.
- Symptoms improved slightly among participants taking placebo, 0.6 points on the UPDRS.
- About two-thirds of participants experienced adverse effects; those taking higher doses experienced them more often.
- The most common side effects were nausea, headache, dizziness and insomnia.
- Of the dosages tested, 145 mg three times per day seemed to provide the best balance between efficacy and safety.
What Does It Mean?
Levodopa is an excellent treatment for the motor symptoms of PD. Researchers continue ways to fine tune methods of giving the medication, such as extending its release via IPX066, to optimize its benefits and minimize side effects. If IPX066 becomes available, this study shows that it may provide another tool for people with PD and their doctors. Although not the focus of this study, scientists are hopeful that in particular, IPX066 will help to ease motor fluctuations, such as dyskinesia.
In the meantime, doctors have other options for helping people with PD who experience fluctuations in the effectiveness of carbidopa-levodopa (“on” and “off” time). In addition to adjusting a person’s medication dosage and schedule, they may add other drugs. These can include monoamine oxidase-B inhibitors, such as rasagiline (Azilect®) and selegiline (Eldepryl®), and dopamine agonists (for example, pramipexole (Mirapex®) or ropinirole (Requip®), or entacapone (Comtan®). In addition, people who experience excellent response to carbidopa-levodopa but experience fluctuations and dyskinesia may benefit from deep brain stimulation.
Source: Parkinson’s Disease Foundation