Comparison of efficacy from phase 3 clinical trials of IPX066, an extended-release carbidopa-levodopa formulation, in Parkinson’s disease (P1.191)

OBJECTIVE: Summarize the efficacy of IPX066 across three phase 3 clinical trials in Parkinson’s disease (PD) BACKGROUND: IPX066 is an investigational, extended-release formulation of carbidopa-levodopa (CD-LD) with an initial absorption rate similar to immediate-release CD-LD (IR), but which also provides an extended duration of therapeutic LD plasma concentrations allowing ~q6h dosing. DESIGN/METHODS: IPX066 was examined in LD-naive patients (APEX-PD: 145mg, 245mg, or 390mg TID vs. placebo for 30 weeks, N=381) and in advanced patients (ADVANCE-PD: IPX066 vs. IR for 13 weeks, N=393; ASCEND-PD: IPX066 vs. CD-LD+entacapone [CL+E] using a 2 week/period crossover, N=91). Efficacy endpoints included Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II+III (all trials); PD diary (ADVANCE-PD/ASCEND-PD); Patient, Clinician Global Impression (PGI, CGI; APEX-PD/ADVANCE-PD); and Subject Preference of Treatment (ASCEND-PD). RESULTS: In APEX-PD, improvements from baseline on UPDRS Parts II+III were ˗11.7 to ˗14.9 points for IPX066 dose groups vs. ˗0.6 for placebo (all P<.0001 vs. placebo) and were maintained throughout the study. IPX066 improved UPDRS Part II+III by ˗5.7 points vs. ˗2.1 by IR (P<.0001) in ADVANCE-PD, and by ˗2.7 points vs. ˗0.3 by CL+E (P=.0233) in ASCEND-PD. IPX066 produced a significantly greater reduction from baseline in “off” time compared to IR (˗2.2 vs. ˗1.0 hr, P<.0001) and CL+E (˗2.1 vs. ˗0.7 hr, P<.0001). “On” time with troublesome dyskinesia did not differ from comparators (P=.6047 vs. IR, P=.3051 vs CL+E). PGI and CGI were significantly improved by all doses of IPX066 vs. placebo (all P<.0001) and vs. IR (P<.0001). In ASCEND-PD, more patients preferred IPX066 (52.4[percnt]) than CL+E (27.4[percnt], P<.001). Across studies, 57.5[percnt] of patients reported 蠅1 adverse event. The most frequent were nausea (10.4[percnt]), dizziness (7.6[percnt]), headache (7.1[percnt]), and dyskinesia (5.4[percnt]). CONCLUSIONS: IPX066 significantly improved PD symptoms with an adverse event profile similar to other dopaminergic therapies. A low proportion of patients reported dyskinesia. SUPPORT: Impax Disclosure: Dr. Elmer has received personal compensation for activities with Lundbeck Research USA, Inc., Novartis, Teva, and UCB Pharma. Dr. Gil has received research support from Impax Laboratories, Inc. Dr. Silver has received personal compensation for activities with Boehringer Ingelheim Pharmaceuticals, Inc., Teva Neuroscience, GlaxoSmithKline, Novartis, Kyowa Hakko Kirin Pharma, Ipsen, Pfizer Inc., Johnson & Johnson, MDS Pharma Services, Accera, Inc., Dr. Hsu has received personal compensation for activities with Impax Laboratories as an employee. Dr. Khanna has received personal compensation for activities with Impax Pharmaceuticals as an employee. Dr. Kell has received personal compensation for activities with Impax Laboratories as an employee. Dr. Gupta has received personal compensation for activities with Impax Laboratories as an employee.