Safety of Levodopa-Carbidopa Intestinal Gel Treatment in Patients with Advanced Parkinson’s Disease Receiving ≥2000 mg Daily Dose of Levodopa

Abstract

Background. Levodopa-carbidopa intestinal gel (LCIG) provides continuous levodopa administration and clinical benefits to patients with advanced Parkinson’s disease (PD). This report evaluates long-term safety and efficacy of high-dose LCIG in PD patients. Methods. Data were collected from several prospective, phase III clinical studies and an observational registry. The phase III program (N = 412) included four multicenter studies: a 12-week, randomized, double-blind study and three open-label studies extending ≥12 months. GLORIA (N = 375) was a 24-month, multicountry, observational registry. LCIG safety (adverse effects (AEs)/adverse drug reactions (ADRs)) and efficacy (modified Unified Parkinson’s Disease Rating Scale (UPDRS) part IV item 32 and 39 scores for “On” time with dyskinesia and “Off” time) were assessed in patients who received ≥2000 mg/day vs <2000 mg/day LCIG. Results. A total of 72 of 412 (17.5%) patients required dosages ≥2000 mg/day LCIG in the phase III program and 47 of 375 (12.5%) patients in GLORIA. Baseline demographics and disease severity were similar between dosage groups with more men in the high-dosage group. Compared with the <2000 mg/day dosage group, patients requiring ≥2000 mg/day LCIG had higher rates of AEs/ADRs including polyneuropathy; improvements in “Off” time and discontinuations due to AEs were similar between dosage groups and lower for discontinuations due to ADRs reported in GLORIA. Conclusions. Patients who require ≥2000 mg/day LCIG exhibited a safety profile comparable to the established safety/tolerability of LCIG with similar clinical improvements. Higher AEs were noted but within what is accepted for LCIG. Continuous administration of LCIG is beneficial to advanced PD patients who require very high doses of levodopa.

The late stage of Parkinson's –results of a large multinational study on motor and non-motor complications

“…Compared to results of other clinical studies, the UPDRS scores and frequencies on non-motor symptoms were higher than in patients with early disease [20,21], but also than in patients who have advanced but not necessarily late disease [22]. However, motor complications including off-periods and dyskinesias, which are characteristic of PD leading to advanced therapies, were present only in 45% of this late stage population and moderate to severe in 7% [22][23][24][25]. Despite a large variety of symptomatic and supportive treatment options, most patients had moderate to severe motor and nonmotor problems.…”

“…As the scale was specifically designed to be more sensitive at the mild stage of the disease [12], it was unclear whether this may have affected its sensitivity at the more severe stages. Subscores were derived for speech (item 18), facial expression (item 19), tremor (item 20 and 21), rigidity (item 22), bradykinesia (items [23][24][25][26], postural instability and gait impairment (PIGD; items 27-29) and body hypokinesia (item 30) [13]. Treatment complications were measured with the UPDRS -part 4 (UPDRS-IV), which were summarized for dyskinesia (items 32-34) and offperiods (items 36-39) [13].…”

Concomitant Medication Usage with Levodopa‐Carbidopa Intestinal Gel: Results from the COSMOS Study

“…This requirement, in addition to limiting AEs to those related to LCIG treatment, likely contributed to the low frequency of AEs in this study versus the rates of AEs in phase 3 studies. 28 …”

Barriers and facilitators of communication about off periods in Parkinson’s disease: Qualitative analysis of patient, carepartner, and physician Interviews

“…These findings suggest an opportunity for Parkinson societies, patient organizations, centers, and physicians to develop off period video and print educational tools for use within clinical encounters, in community settings, and for patient and carepartner self-education. Subsequent to the conduct of this study, the Parkinson’s Foundation published “Managing PD Mid-Stride,” a booklet with text and figure-based education regarding off periods that addresses some of the needs identified by study participants [29]. Educational tools can potentially improve health related quality of life in PD [30] and medication adherence [31].…”