IPX203 shows sustained safety, efficacy in RISE-PD extension trial

Therapy is an extended-release formulation of carbidopa and levodopa

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Using IPX203, an extended-release formulation of carbidopa/levodopa (CD/LD), was associated with a sustained control of symptoms for Parkinson’s disease patients who participated in the open-label extension of the RISE-PD Phase 3 trial.

Final results from the nine-month extension study (NCT03877510) indicate dose adjustments and side effects were most common in the first months of treatment, and tended to stabilize after that. The study, “Safety and Efficacy of IPX203 in Parkinson’s Disease: The RISE-PD Open-Label Extension Study,” was published as a brief report in Movement Disorders. It was sponsored byIPX203’s developer, Amneal Pharmaceuticals.

CD/LD is a standard combination for treating Parkinson’s. Levodopa is a precursor to dopamine, the brain signaling chemical that’s lost in the neurodegenerative disease. Carbidopa helps prevent levodopa’s conversion to dopamine in the bloodstream, enabling more to reach the brain where it’s needed.

IPX203 is an extended-release formulation of this treatment duo that contains immediate-release granules of CD/LD as well as extended-release coated beads of levodopa.

The aim is to enable the medication to stay at clinically relevant doses in the bloodstream longer, extending motor symptom control relative to standard, immediate-release CD/LD therapies such as Sinemet. This could also help prevent off episodes, or motor fluctuations — periods when symptoms return between levodopa doses — and increase on episodes, when symptoms are well controlled without troublesome involuntary movements, called dyskinesia.

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RISE-PD and its extension study

In the RISE-PD trial (NCT03670953), 506 patients with advanced Parkinson’s who were having motor fluctuations were randomly assigned to receive oral IPX203 or a generic version of Sinemet for 13 weeks (a little over three months) after a dose adjustment phase.

IPX203 led to significantly more good on time and less off time compared to the immediate-release therapy, according to results that were published last year.

This was achieved with fewer daily doses; those on IPX203 took it an average of three times a day, whereas the immediate-release alternative was used an average of five times.

After completing the trial, 419 participants opted to continue in the extension study where all received IPX203 for nine more months.

The final published results, similar to a previous interim analysis, indicate IPX203 remained safe and effective throughout the extension study.

The dosing frequency was stable over nine months, with a mean of about three doses a day. Changes in the dosing regimen were most common in the first months of treatment and tended to stabilize afterward.

Scores on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), a measure of the severity of Parkinson’s symptoms and their life quality impacts, were not notably changed, nor were scores on patient- and clinician-reported outcomes. Likewise, measures of quality of life, anxiety, sleep, and others were stable, indicating effective symptom control overall and 81.7% of patients reported being at least somewhat satisfied with the treatment after nine months.

A little over half the patients had at least one treatment-emergent side effect, with 25 people stopping treatment early due to side effects.

Most side effects were mild or moderate and occurred within the first three months of treatment. The most common ones determined to be related to IPX203 were dyskinesia (4.5%) and nausea (1%), which “are commonly associated with [Parkinson’s] therapies,” according to the researchers. Six deaths occurred, one of which was a drowning that was attributed to the treatment.

Altogether, the trial’s results suggest IPX203  “provides maintained efficacy and is generally safe and well tolerated,” the researchers wrote.

The therapy was under review by the U.S. Food and Drug Administration (FDA) earlier this year, backed by data from RISE-PD, but the agency said it needed additional safety data before it could make its final decision. Specifically, while information related to the safety and pharmacological properties of one main ingredient, levodopa, were sufficient, they were found lacking for carbidopa.

Amneal has since shared additional data analyses with the FDA and requested another meeting with the agency.