Objective: Evaluate the efficacy and dosing of IPX066 in patient groups taking concomitant Parkinson’s disease (PD) medication, using post hoc subgroup analyses.

Background: IPX066 is an extended-release, oral, capsule formulation of carbidopa-levodopa (CD-LD). Following an initial peak at about one hour, plasma levodopa concentrations are maintained for about 4-5 hours. IPX066 has demonstrated improvement in motor symptoms in early and advanced PD.

Methods: ADVANCE-PD was a randomized, double-blind, active-controlled, Phase 3 study to examine the safety and efficacy of IPX066 vs. immediate-release (IR) CD-LD. An open-label, 6 week conversion period to IPX066 preceded 13-weeks of double-blind treatment. To evaluate the effect of concomitant medication on IPX066 dosing and response to IPX066, we analyzed final dose ratios (IPX066:IR) and dose frequency at the end of dose conversion, and efficacy measures (PD diary and Unified PD Rating Scale [UPDRS] Parts II [activities of daily living] + III [motor score]) in subgroups based on the concomitant use or non-use of dopaminergic agonists (DA), monoamine oxidase-B (MAO-B) inhibitors, or amantadine.

Results: 450 patients entered dose conversion to IPX066; 393 completed and were randomized. In the overall study, IPX066 improved “off” time (P<.0001), “on” time without troublesome dyskinesia (P=.0002), and UPDRS Parts II+III scores (P<.0001) vs. IR CD-LD. At the end of conversion, final dose ratios were 2.0-2.1 (IPX066:IR) regardless of the concomitant medication subgroup. Across subgroups, mean dose frequencies for IPX066 were 3.5-3.6 doses/day vs. 4.7-5.2 doses/day of IR at study baseline. Numerical improvements from baseline in PD diary measures and UPDRS Parts II+III were seen with IPX066 vs IR CD-LD in each subgroup. Improvements in “off” time and “on” time without troublesome dyskinesia were significant (P<.05) for IPX066 vs. IR in each subgroup, except for the group using concomitant amantadine (P>.50). IPX066 did not significantly worsen “on” time with troublesome dyskinesia vs. IR in any subgroup (P>.11).

Conclusions: The concomitant use or non-use of adjunctive PD medications did not affect the final mean levodopa dose ratio or dose frequency after conversion to IPX066 from IR CD-LD, nor did it affect the efficacy or degree of troublesome dyskinesias when IPX066 was compared to IR CD-LD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/extended-release-carbidopa-levodopa-ipx066-dosing-and-efficacy-with-concomitant-medication-use-in-parkinsons-disease/