GSK announces positive topline results of Phase lll study of IPX066 in advanced Parkinson's disease

GlaxoSmithKlineGlaxoSmithKline (GSK) announced positive, top-line results of the ADVANCE-Parkinson's Disease (PD) Phase III clinical study, conducted by Impax Pharmaceuticals, of IPX066 versus immediate-release (IR) carbidopa-levodopa (CD-LD) in advanced PD patients experiencing motor fluctuations. IPX066 is an investigational extended release (ER) CD-LD product which is being developed by Impax in collaboration with GSK. Under the terms of a development and commercialisation agreement, Impax will develop and commercialise IPX066 in the United States and Taiwan, and GSK will develop and commercialise IPX066 in all other markets throughout the world.

The primary endpoint of this study was the percentage of "off time" during waking hours. "Off time" is the functional state when patients' medication effect has worn off and there is a return of Parkinson symptoms. IPX066 demonstrated a 37% decrease in off-time from baseline vs. a 17% decrease from baseline for IR CD-LD (p<0.0001).

The study enrolled 471 subjects on a stable regimen of IR CD-LD who were first entered into a dose-adjustment phase of their IR CD-LD, then switched to open label IPX066 after which they were then randomised to double-blind IPX066 or IR CD-LD. Subjects switched to IPX066 experienced a total reduction in off-time from baseline of more than 2 hours during waking hours. This effect was maintained in those patients randomised to IPX066 during the blinded study portion, while "off time" increased by 1 hour in the group randomised to treatment with IR CD-LD (p<0.0001). In addition, during double-blind treatment, patients on IPX066 experienced an increase of 1.9 hours in "on time" without dyskinesia, compared to an increase of 0.8 hours for IR CD-LD as measured from study entry (p=0.0002).

Efficacy improvements on IPX066 were corroborated by similar improvements in additional clinical and patient-reported outcome endpoints. These included 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 IPX066 compared to IR CD-LD (p<0.0001 for all comparisons)., IPX066 demonstrated significant improvement over IR CD-LD on quality-of-life (QOL) measures such as the PDQ-39 (p<0.035) and the modified Rankin Test (p<0.006).

IPX066 was generally well tolerated, and during the double-blind portion of the trial had an adverse event (AE) rate of 43% compared to 40% for IR CD-LD. The most common AEs reported for IPX066 included: insomnia, nausea, fall, dizziness, and dyskinesia (no event was associated with a greater than 3.5% overall incidence). The rate of related serious AEs was comparable, with one subject in each treatment arm reporting serious treatment-related AEs in the double-blind treatment phase.

Full results from the ADVANCE-PD study will be presented at an upcoming scientific meeting.

About the GSK/Impax collaboration
GSK and Impax Pharmaceuticals, the brand products division of Impax Laboratories, Inc. (Impax), announced an agreement for the development and commercialisation of IPX066, outside the United States and Taiwan, in December 2010. Under the terms of the agreement, GSK received an exclusive license to develop and commercialise IPX066 throughout the world except in the U.S. and Taiwan. Impax will complete the current Phase III program for IPX066, which includes the ADVANCE-PD study.

About the ADVANCE-PD Study and IPX066 Development Program
The ADVANCE-PD study is the second of three Phase III studies. The study is a randomised, double-blind, active-control, parallel-group Phase III study of the safety and efficacy of IPX066 versus IR CD-LD in advanced PD patients with motor fluctuations. The trial enrolled 471 subjects in North America and Europe of which 393 subjects were randomised to participate in the 13-week comparison of IPX066 versus IR CD-LD. Prior to randomisation, subjects on a stable IR CD-LD dose regimen entered a 3-week dose-adjustment or dose optimisation period for IR CD-LD, followed by a 6-week dose-conversion period to IPX066. Subjects were instructed to take IPX066 three times a day.

Impax previously announced the results of APEX-PD Phase III study in early PD. APEX-PD was a randomised, double-blind, placebo-controlled, parallel group, fixed-dose study comparing 3 doses of IPX066 to placebo in 381 patients with early PD.

Additionally, Impax is conducting the ASCEND-PD comparative study of IPX066 and carbidopa-levodopa and entacapone, which is currently enrolling subjects.

An Open Label Extension study for subjects from the ADVANCE-PD and APEX-PD studies is also ongoing.

About IPX066
IPX066 is an investigational CD-LD product with an enhanced pharmacokinetic profile. The IPX066 pharmacokinetic profile has the potential to offer reliable control of PD symptoms, such as the reduction in "off time" throughout the day, which has been observed in preliminary studies of IPX066.

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

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

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