Longitudinal Change in Quality of Life in Neurological Disorders Measures Over 3 Years in Patients with Early Parkinson's Disease.

BACKGROUND: The Quality of Life in Neurological Disorders (Neuro-QoL) is a publicly available health-related quality-of-life measurement system. OBJECTIVE: The aim of this study was to evaluate the utility of Neuro-QoL item banks as outcome measures for clinical trials in Parkinson's disease. METHODS: An analysis of Neuro-QoL responsiveness to change and construct validity was performed in a multicenter clinical trial cohort. RESULTS: Among 310 participants over 3 years, changes in five of eight Neuro-QoL domains were significant (P < 0.05) but very modest. The largest effect sizes were seen in the cognition and mobility domains (0.35-0.39). The largest effect size for change over the year in which levodopa was initiated was -0.19 for lower extremity function-mobility. For a similarly designed clinical trial, estimated sample size required to demonstrate a 50% reduction in worsening ranged from 420 to more than 1000 participants per group. CONCLUSIONS: More sensitive tools will be required to serve as an outcome measure in early Parkinson's disease. © 2021 International Parkinson and Movement Disorder Society.

A 12-month, dose-level blinded safety and efficacy study of levodopa inhalation powder (CVT-301, Inbrija) in patients with Parkinson's disease.

INTRODUCTION: CVT-301 (Inbrija®) is a levodopa inhalation powder for on-demand treatment of OFF episodes in Parkinson's disease patients treated with carbidopa/levodopa. Safety and efficacy results of a 12-month, dose-level blinded extension study of a phase 3 trial (SPAN℠-PD) of CVT-301 are presented. METHODS: Patients were receiving oral carbidopa/levodopa and adjunctive CVT-301 treatment, blinded to dose (60 mg or 84 mg, N = 325). Study visits occurred every 3 months. Pulmonary function was assessed by spirometry. Other safety assessments included dyskinesia and adverse events (AEs). Secondary objectives of the study included maintenance of improvement assessments for occurrence of an ON state during the 60-min post-dose period, change in total daily OFF time, and Patient Global Impression of Change (PGIC). RESULTS: Most frequent AEs (≥5%) were cough (15.4%), fall (13.1%), upper respiratory tract infection (7.1%), and dyskinesia (5.1%). Severe AEs (>1 event) were cough (1.9%) and dyskinesia (0.6%). Twelve-month mean changes from baseline for FEV1, FVC, and DLCO were -0.092 L, -0.097 L, and -0.922 mL/min/mmHg, respectively. At 12 months, 73.0% of patients on 84 mg achieved an ON state within 60 min. Total daily OFF time was reduced by 0.55 h (month 1) and 0.88 h (month 12) for the 84 mg dose. Percentage of patients self-reported as improved by PGIC was 65.5-91.9% over 12 months. CONCLUSION: CVT-301 was generally well-tolerated. Twelve-month decline in pulmonary function was consistent with a prior PD control group. Exploratory efficacy results showed CVT-301 maintained improvement at achieving ON states in patients experiencing OFF episodes, decreasing daily OFF time, and maintaining improvement in PGIC.

Conversion to carbidopa and levodopa extended-release (IPX066) followed by its extended use in patients previously taking controlled-release carbidopa-levodopa for advanced Parkinson's disease.

BACKGROUND: IPX066 (Rytary®; carbidopa and levodopa [CD-LD] extended-release capsules) was designed to achieve therapeutic LD plasma concentrations within 1h of dosing and maintain LD concentrations for a prolonged duration in early or advanced Parkinson's disease (PD). METHODS: In this open-label study, patients underwent 6weeks of conversion to IPX066 from their prior controlled-release (CR)±immediate-release (IR) CD-LD therapy and 6months of maintenance (with an additional 6months of IPX066 at some sites). Clinical utility was assessed at both the end of conversion and maintenance. RESULTS: Among 43 patients initiated on IPX066, 33 completed conversion. The mean LD conversion ratio was 1.8 among 30 patients previously on CR plus IR (and 1.5 among 3 previously taking CR alone). The mean IPX066 dosing frequency was 3.5times/day compared with 2.6times/day for CR plus 4.6times/day for IR previously (and 4.7times/day for CR alone). By patient and clinician global improvement ratings after 6-month maintenance, ≥43.8% of patients were much or very much improved from their previous treatment, and ≥68.8% were at least minimally improved. Adverse events were consistent with those reported in prior IPX066 studies. CONCLUSIONS: These results suggest that advanced PD patients using CR CD-LD±IR can be safely converted to IPX066, with high likelihood of achieving a stable regimen, less frequent LD dosing, and improved overall clinical benefit. TRIAL REGISTRATION: Clinicaltrials.govNCT01411137.

A randomized, double-blind, placebo-controlled trial of coenzyme Q10 in Huntington disease.

OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. RESULTS: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. CONCLUSIONS: These data do not justify use of CoQ as a treatment to slow functional decline in HD. CLINICALTRIALSGOV IDENTIFIER: NCT00608881. CLASSIFICATION OF EVIDENCE: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.