3 research outputs found
Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinsonâs Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study
\ua9 2023, The Author(s). Introduction: Foslevodopa/foscarbidopa, a soluble formulation of levodopa/carbidopa (LD/CD) prodrugs for the treatment of Parkinsonâs disease (PD), is administered as a 24-hour/day continuous subcutaneous infusion (CSCI) with a single infusion site. The efficacy and safety of foslevodopa/foscarbidopa versus oral immediate-release LD/CD was previously demonstrated in patients with PD in a 12-week, randomized, double-blind, phase 3 trial (NCT04380142). We report the results of a separate 52-week, open-label, phase 3 registrational trial (NCT03781167) that evaluated the safety/tolerability and efficacy of 24-hour/day foslevodopa/foscarbidopa CSCI in patients with advanced PD. Methods: Male and female patients with levodopa-responsive PD and ⼠2.5 hours of âOffâ time/day received 24-hour/day foslevodopa/foscarbidopa CSCI at individually optimized therapeutic doses (approximately 700â4250 mg of LD per 24 hours) for 52 weeks. The primary endpoint was safety/tolerability. Secondary endpoints included changes from baseline in normalized âOffâ and âOnâ time, percentage of patients reporting morning akinesia, Movement Disorder Society Unified Parkinsonâs Disease Rating Scale (MDS-UPDRS), Parkinsonâs Disease Sleep Scaleâ2 (PDSS-2), 39-item Parkinsonâs Disease Questionnaire (PDQ-39), and EuroQol 5-dimension questionnaire (EQ-5D-5L). Results: Of 244 enrolled patients, 107 discontinued, and 137 completed treatment. Infusion site events were the most common adverse events (AEs). AEs were mostly nonserious (25.8% of patients reported serious AEs) and mild/moderate in severity. At week 52, âOnâ time without troublesome dyskinesia and âOffâ time were improved from baseline (mean [standard deviation (SD)] change in normalized âOnâ time without troublesome dyskinesia, 3.8 [3.3] hours; normalized âOffâ time, â3.5 [3.1] hours). The percentage of patients experiencing morning akinesia dropped from 77.7% at baseline to 27.8% at week 52. Sleep quality (PDSS-2) and quality of life (PDQ-39 and EQ-5D-5L) also improved. Conclusion: Foslevodopa/foscarbidopa has the potential to provide a safe and efficacious, individualized, 24-hour/day, nonsurgical alternative for patients with PD. Trial Registration Number: ClinicalTrials.gov identifier NCT03781167
The Total Deviation Index estimated by Tolerance Intervals to evaluate the concordance of measurement devices
Background In an agreement assay, it is of interest to evaluate the degree of agreement between the different methods (devices, instruments or observers) used to measure the same characteristic. We propose in this study a technical simplification for inference about the total deviation index (TDI) estimate to assess agreement between two devices of normally-distributed measurements and describe its utility to evaluate inter- and intra-rater agreement if more than one reading per subject is available for each device. Methods We propose to estimate the TDI by constructing a probability interval of the difference in paired measurements between devices, and thereafter, we derive a tolerance interval (TI) procedure as a natural way to make inferences about probability limit estimates. We also describe how the proposed method can be used to compute bounds of the coverage probability. Results The approach is illustrated in a real case example where the agreement between two instruments, a handle mercury sphygmomanometer device and an OMRON 711 automatic device, is assessed in a sample of 384 subjects where measures of systolic blood pressure were taken twice by each device. A simulation study procedure is implemented to evaluate and compare the accuracy of the approach to two already established methods, showing that the TI approximation produces accurate empirical confidence levels which are reasonably close to the nominal confidence level. Conclusions The method proposed is straightforward since the TDI estimate is derived directly from a probability interval of a normally-distributed variable in its original scale, without further transformations. Thereafter, a natural way of making inferences about this estimate is to derive the appropriate TI. Constructions of TI based on normal populations are implemented in most standard statistical packages, thus making it simpler for any practitioner to implement our proposal to assess agreement
Correction: Continuous Subcutaneous Foslevodopa/Foscarbidopa in Parkinsonâs Disease: Safety and Efficacy Results From a 12-Month, Single-Arm, Open-Label, Phase 3 Study (Neurology and Therapy, (2023), 12, 6, (1937-1958), 10.1007/s40120-023-00533-1)
\ua9 2023, The Author(s).In the sentences beginning âAt baseline,âŚâ and âThe reduction of early morningâŚâ in the section âEfficacyâ under the heading âResultsâ in this article, the n/N values â129/238, 20/139, 25/125 and 56/125â were incorrect and the correct sentences should have read as follows: At baseline, 77.7% (n/N = 129/166) of patients experienced morning akinesia, which decreased to 19.2% (n/N = 20/104) at week 26, and 27.8% (n/N = 25/90) at week 52. The reduction of early morning âOffâ time was accompanied by a marked increase in the proportion of patients reporting âOnâ time without dyskinesia on awakening (62.2%; n/N = 56/90 at week 52) (Fig. 3). In the sentence beginning âThe reduction of âOffâ time is particularly exemplified byâŚâ under the heading âDiscussionâ, the value â(changed from 17.5% at baseline to 63.0% at week 52)â should have read â(changed from 17.5% at baseline to 62.2% at week 52).â The original article has been corrected