The Long-Term Safety of an Oral, Extended-Release Capsule Formulation of Carbidopa-Levodopa (IPX066) in Patients with Early and Advanced Parkinson's Disease

Study results show that IPX066 demonstrated a favorable tolerability profile throughout extended dosing in early Parkinson's disease (PD) and during the long-term management of patients with advanced PD.

Two studies evaluated the long-term safety of an oral, extended-release, capsule formulation of carbidopa-levodopa (IPX066) in patients with early and advanced Parkinson's disease (PD), according to research presented at the 65th Annual Meeting of the American Academy of Neurology.

The investigational agent, IPX066, contains carbidopa-levodopa in a one-to-four ratio and is designed to provide a rapid increase in plasma concentration followed by stable concentrations. This could be an important advance that could allow some patients to take their medication as few as three times per day. In previously conducted studies in patients with early PD, IPX066 demonstrated statistically significant benefit compared with placebo using multiple measures, including Parts II and III of the Unified Parkinson's Disease Rating Scale (UPDRS). Compared with immediate-release carbidopa-levodopa, IPX066 has previously demonstrated improvements in daily off-time for patients with PD and motor fluctuations.

In a 30-week, phase III, open-label extension study, Paul Nausieda, MD, of the Wisconsin Institute for Neurologic and Sleep Disorders in Milwaukee, and colleagues evaluated the long-term safety of fixed doses of 145, 245, or 390 mg TID extended-release carbidopa-levodopa capsules in 300 patients with early PD who were not taking dopamine agonists (DA) or catechol-O-methyltransferase (COMT) inhibitors. The efficacy of IPX066, as demonstrated using UPDRS Parts II and III, was maintained for all patients who completed the 30 weeks of treatment. Overall 95% of all eligible patients who entered the extension study completed it. For all patients, the median total daily dose was 720 mg, and most patients only needed to take the drug three times per day. The most frequently reported adverse events were nausea (5.6%), insomnia (5.6%), hypertension (4.1%), and headache (3.7%).

In the second open-label extension study, Aaron Ellenbogen, MD, of the Quest Research Institute in Farmington Hills, Michigan, and colleagues evaluated the safety of IPX066 over a 9-month period in 395 patients with advanced PD who were experiencing motor fluctuations. Most patients (88%) were able to take IPX066 three or four times per day, with the median IPX066 daily dose being approximately 1450 mg. For patients who completed the nine-month extension, the efficacy of IPX066, as demonstrated on the UPDRS Parts II and III, was maintained. Overall, 90% of all eligible patients who entered the extension study completed it. Here, the most frequently reported adverse events were dyskinesia (6.9%), fall (6.6%), pain in extremity (3.7%), hallucinations (3.4%), and arthralgia (3.2%).

“Overall, IPX066 demonstrated a favorable tolerability profile throughout extended dosing in early PD and during the long-term management of patients with advanced PD. During open-label administration, the frequency of adverse events reported was typical of this patient population and typical of those observed in the original IPX066 trials,” the authors concluded.

These studies were supported by Impax Pharmaceuticals.