Introduction: In a pivotal study, apomorphine sublingual film (APL; KYNMOBI Ò ) was an effective and generally well-tolerated ondemand treatment of ''OFF'' episodes in patients with Parkinson's disease (PD), approved across the dose range of 10-30 mg. Pharmacokinetics and comparative bioavailability of APL and two subcutaneous (SC) apomorphine formulations (SC-APO [APOKYN Ò ] and SC-APO-GO [APO-go Ò PEN]) were evaluated in a randomized, threeway crossover, open-label study (NCT03292016). Methods: Patients with PD and ''OFF'' episodes received an open-label randomized sequence of single doses of SC-APO and SC-APO-GO at the currently prescribed dose (2/3/4/5 mg) and APL doses with similar plasma exposure (15/20/25/ 30 mg) with C 1-day washout between formulations. Plasma pharmacokinetics of apomorphine and apomorphine sulfate (major inactive metabolite) were measured 0-6 h postdose. Results: Median time to maximum plasma concentration (t max ) of apomorphine was 0.63-0.75 h for APL and 0.25-0.38 h for SC-APO and SC-APO-GO. Geometric mean maximum plasma concentration (C max ) of apomorphine was 4.31-11.2 ng/ml across APL doses and was generally lower compared with SC apomorphine formulations within dose groups. Area under the concentration-time curve from time 0 to infinity (AUC ? ) was similar across apomorphine formulations within most dose groups. Relative bioavailability of APL was * 17% of SC apomorphine by AUC ? ; SC-APO and SC-APO-GO had similar bioavailability (98% and 83% by AUC ? and C max , respectively). Apomorphine sulfate exposure was * three-fold higher for
This study confirmed the beneficial effect of abobotulinumtoxinA on CD in routine clinical practice as measured by improvements in TWSTRS and PGIC. No new safety concerns were identified.
Background:Due to the short half-life of levodopa, immediate-release carbidopa-levodopa (IR CD-LD) produces fluctuating LD concentrations, contributing to a risk of eventual motor complications. IPX066 was designed to rapidly attain therapeutic LD concentrations and maintain them to allow a dosing interval of ∼6 hours.Objective:To extensively analyze the dosing data collected in IPX066 studies during open-label conversions from IR CD-LD alone or with entacapone (CLE) and identify patterns relevant for managing conversion in the clinical setting.Methods:Patients had ≥2.5 hours/day of “off” time despite a stable IR or CLE regimen. Suggested initial dosing conversion tables based on prior LD daily dosage were provided.Results:Of 450 patients previously treated with IR CD-LD and 110 with CLE, 87.3% and 82.7% completed conversion to IPX066, respectively. At the end of conversion, average IPX066 LD daily dosages were higher than pre-conversion dosages, with a mean conversion ratio of 2.1±0.6 for IR CD-LD and 2.8±0.8 for CLE; >90% of patients took IPX066 3 or 4 times/day, compared with a median of 5 times/day at baseline in both studies. After conversion, daily “off” time significantly decreased, with no significant increase in troublesome dyskinesia. The most common adverse event reported during conversion was nausea, with an incidence of 5.3% for conversion from IR and 7.3% from CLE.Conclusions:Among PD patients with substantial “off” time, a majority were safely converted to IPX066. The sustained LD profile from the IPX066 formulation allowed an increase in LD dose accompanied by improved motor functions, without increased troublesome dyskinesia.
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