Even at the highest modal dose range, findings from the phase 3 RISE-PD trial showed that IPX203 did not increase safety risks for patients with Parkinson disease over time.
New data from the phase 3 RISE-PD clinical trial (NCT0300788) assessing IPX203 (Amneal Pharmaceuticals), an oral formulation of carbidopa/levodopa (CD/LD) extended-release capsules, revealed an association between longer exposure to IPX203 and a decrease in the occurrence of treatment emergent adverse events (TEAEs).1 These findings demonstrated the safety and tolerability of IPX203 across various dosage ranges, even at the highest doses, over an extended period of use.
For at least 12 months, investigators had 179 patients with PD exposed to IPX203 continuously at a wide distribution of doses, with modal doses ranging from 140/560 mg CD-LD to 1260/5040 mg CD-LD a day. As participants were grouped into 4 quartiles (each quartile, n ≈ 45), the modal dose ranges were 560-<1050 mg, 1050-<1470 mg, 1470-<2100 mg and 2100-5040mg LD/day. Findings showed a decrease in the number of patients with TEAEs as the exposure time increased compared with the number of patients with TEAEs by duration of exposure, at any modal dose range.
These findings were presented at the
After
IPX203’s new drug application (NDA) was supported by findings from RISE-PD which demonstrated the therapy’s ability to provide significantly more ON time per day than IR CD/LD. The NDA was originally accepted in November 2022 and the full results of the trial were published in JAMA Neurology in August 2023, months after the CRL was issued.3
Results from the trial showed that the agent met its primary end points, as those dosed with IPX203 (n = 256) 3 times per day had a statistically significant improvement of 0.53 hours (95% CI, 0.09-0.97; P = .02) in daily good ON time relative to those on IR CD/LD (n = 250), who were dosed 5 times per day.3 Led by
The secondary end point of change from baseline in OFF-time in hours per day showed that IPX203 treatment resulted in significantly less OFF-time compared with IR CD/LD (difference in least square [LS] means, –0.48; 95% CI, –0.90 to –0.06; P = .03). Between the groups, 29.7% and 18.8% of patients on IPX203 and IR CD/LD, respectively, rated themselves as much improved or very much improved on PGI-C (P = .002).
Among those treated with IPX203, the most frequently reported treatment emergent adverse events were nausea (4.3%), anxiety (2.7%), and dizziness (2.3%), while those on IR CD/LD mostly experienced fall (3.6%), urinary tract infection (3.2%), and back pain (2.8%). No clinically relevant treatment group differences were noted for laboratory parameters, vital signs, and electrocardiogram results. There were no deaths reported as well.
