Extended release carbidopa-levadopa safe and effective in treatment of advanced Parkinson’s

Hayward, CA (March 15, 2011) — The ADVANCE-Parkinson’s Disease Phase III clinical study has demonstrated the safety and effectiveness of extended release carbidopa-levadopa (investigational drug IPX066) versus immediate release carbidopa-levodopa, Impax Pharmaceuticals announced today.

The ADVANCE-PD results demonstrated that, in several measures of patients with advanced Parkinson’s disease, extended release carbidopa-levadopa (CD-LD) produced significantly improved control of motor symptoms compared to immediate release CD-LD, currently the gold standard for treating advanced Parkinson’s.

USF Health’s Dr. Robert Hauser was a study investigator.

The primary endpoint of this comparison study of extended release CD-LD to immediate release CD-LD was the percentage of “off time” during waking hours. Extended release CD-LD demonstrated a 37 percent improvement from baseline compared to a 17 percent improvement from baseline for immediate release CD-LD. “Off time” is the functional state when patients’ medication effect has worn off and there is a return of Parkinson’s symptoms.

The study enrolled 471 patients on a stable regimen of immediate release CD-LD who were first entered into a dose-adjustment phase of their immediate release CD-LD, followed by a conversion to extended release. The patients were then randomized to either extended release or immediate release medication. Subjects converted to extended release CD-LD experienced a reduction from baseline of more than two hours in total “off time” during waking hours, and this effect was maintained in the group then randomized to extended release during the blinded study portion. While the group treated with immediate release CD-LD achieved similar improvement during conversion to immediate release, “off time” worsened by one hour during double blind treatment with immediate release CD-LD. In addition, during double-blind treatment, subjects experienced similar results in “on time” without troublesome dyskinesia with an increase of 1.9 hours for extended release compared to an increase of 0.8 hours for immediate release as measured from study entry.

Additional clinical and patient-reported outcome measures in the study consistently demonstrate the improved extended release medication’s effectiveness profile when compared to immediate release. This includes the Unified Parkinson’s Disease Rating Scale (UPDRS), Clinician Global Impression of Change (CGI) and Patient Global Impression of Change (PGI), which also demonstrated significant improvements in treatment with extended release compared to immediate release. In quality-of-life (QOL) measures, extended release CD-LD also demonstrated significant improvement over immediate release CD-LD.

“Impax Pharmaceuticals is excited to report these positive results for the ADVANCE-PD trial demonstrating the clinical benefits of IPX066 over IR CD-LD, which is the gold standard in treating advanced PD,” stated Dr. Suneel Gupta, Impax Pharmaceuticals’ Chief Scientific Officer.

Extended release CD-LD was generally well tolerated, and during the double-blind portion of the trial had an adverse event rate of 43 percent compared to 40 percent for immediate release CD-LD. The most common adverse effects reported for the extended-release medication included insomnia, nausea, fall, dizziness, and dyskinesia (no event was associated with a greater than 3.5 percent overall incidence). The rate of related serious adverse effects was comparable, with one subject in each treatment arm reporting serious treatment-related events in the double-blind treatment phase.

“There is a major unmet need in patients with advanced Parkinson’s disease for a therapy that can consistently extend and improve motor symptom control through the day and enhance quality of life.” said ADVANCE-PD study investigator Robert A. Hauser, MD, professor of neurology, molecular pharmacology, and physiology and director of the Parkinson’s Disease & Movement Disorders Center at the University of South Florida. “In the ADVANCE-PD study, daily ‘off time’ was reduced without worsening of dyskinesia, and both patients and clinicians reported overall improvement. The magnitude of benefit observed with extended release carbidopa levadopa was clinically significant and results indicate that Parkinson’s disease patients should be able to enjoy improved control of their motor symptoms and a better quality of life.”

Impax Pharmaceuticals plans to present complete results of the ADVANCE-PD study at an upcoming scientific meeting.

Parkinson’s Disease is a chronic neurodegenerative movement disorder affecting over three million people in the US, Europe, and Japan.

About Impax Laboratories, Inc.
Impax Laboratories, Inc. is a technology-based specialty pharmaceutical company applying its formulation expertise and drug delivery technology to the development of controlled-release and specialty generics in addition to the development of branded products. Impax markets its generic products through its Global Pharmaceuticals division and markets its branded products through the Impax Pharmaceuticals division. Additionally, where strategically appropriate, Impax has developed marketing partnerships to fully leverage its technology platform. Impax is headquartered in Hayward, California, and has a full range of capabilities in its Hayward, Philadelphia and Taiwan facilities. For more information, please visit the Company’s Web site at: www.impaxlabs.com.