To assess the effect of concomitant Parkinson’s disease (PD) medication use on the efficacy of CREXONT (IPX203).

Extended-release (ER) carbidopa-levodopa (CD-LD) and concomitant medications like dopamine agonists (DA) are routinely used to manage motor fluctuations in PD. CREXONT is a novel oral ER CD-LD formulation. In the RISE-PD clinical trial, CREXONT has demonstrated significant increase in “Good On” time (GOT) vs immediate-release (IR) CD-LD, in PD patients with motor fluctuations.

RISE-PD was a randomized, double-blind, active-controlled, phase 3 study examining the safety and efficacy of CREXONT vs IR CD-LD. It included a 4-week open-label dose-conversion from IR CD-LD to CREXONT. To evaluate the impact of concomitant DA therapy on CREXONT's efficacy, we analyzed GOT in subgroups based on their levodopa-equivalent-daily-dose (LEDD) of DA, comparing GOT values at the end of CREXONT conversion period to study entry.

In the full patient population, conversion from IR CD-LD to CREXONT improved GOT by 1.74h while reducing average dosing frequency from 5 to 3 times/day.

Subgroup analysis showed that patients on no DA or DA LEDD 1-100 demonstrated increases in GOT of 2.35h and 2.72h, respectively. DA LEDD 101-200 led to 2.36h GOT gain, 201-300 to 1.50h gain, and DA LEDD>300 to 1.37h gain. ANOVA revealed a significant effect of DA dose on GOT gain (p<0.01). An unbiased thresholding algorithm identified the impactful cutoff point at 200 DA LEDD. Using this threshold, we observed a significant difference between the low (≤200mg DA LEDD) and high (>200mg DA LEDD) groups, with GOT gains of 2.40h and 1.45h, respectively (p<0.01).

Converting patients from IR CD-LD to CREXONT improved GOT in all subgroups, with the highest benefit in those receiving 200mg or less DA LEDD. While patients on higher DA doses also benefited from conversion, GOT gain was reduced by 40% compared to the low dose group.