Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial

Comparison of IPX066 with carbidopa–levodopa plus entacapone in advanced PD patients

“…The effects are robust, as demonstrated by a post-hoc sensitivity analysis employing conservative imputation methods. The effects are also consistent with the 1.2 h greater reduction in "off" time observed in a 13-week randomized, double-blind comparison of IPX066 and CD-LD IR in advanced, fluctuating PD [21].…”

“…For the initial conversion from CLE or CL þ E to IPX066, the dose-conversion table provided in the study protocol was based on the patient's total daily LD dosage in CLE or CL þ E at study entry. As entacapone is known to increase LD bioavailability by approximately 35%e40% [23], the initial IPX066 doses provided by the table were approximately 30% higher than had been provided for converting CD-LD IR to IPX066 [21].…”

Continuous dopaminergic delivery to minimize motor complications in Parkinson’s disease

“…These data are preliminary given the small study size, open-label design and short treatment period. However, in a recently published Phase III study of 393 patients over a 13-week period using a randomized blinded doubledummy design, IPX066 (mean: 3.6 daily doses) reduced 'off ' time by an average of 1.17 h (95% CI: 0.66-1.69) more than CD-LD IR (5.1 daily doses) [70]. Adverse events were minor and similar between the two groups.…”

New Developments in the Treatment of Parkinson's Disease: Bridging the gap between Medical and Surgical Therapy for PD

“…This is not unexpected, as the major side effects of nausea, vomiting, diarrhea, dizziness, falls, dyskinesia, confusion, and insomnia are likely secondary to dopaminergic activity. 11,13,14,15,16,17 Slightly increased side effect frequency in the RYTARY arms may be due to higher total doses of levodopa, rapid dose titration, or the need for post-synaptic adjustments to the change in pharmacokinetics. Patients who completed the above trials were eligible to enroll in a nine-month open label extension by Waters et al, which confirmed the overall tolerability and safety of RYTARY over a longer treatment duration.…”

“…19 Conversion from CD-LD to RYTARY should be based on a patient's total daily dose of immediate release levodopa. Slightly less than a two-to-one ratio of levodopa in RYTARY to immediaterelease CD-LD was used in the Hauser et al trials, 11,14,15 and is the recommended dosing conversion in the FDA prescribing information. 20 In addition, patients often need further increases in doses after the initial switchover.…”