BackgroundNocturnal symptoms are common in Parkinson’s disease (PD), which greatly affect the quality of life but are often overlooked in clinical settings. Treatment strategies that provide sustained dopaminergic stimulation may have sleep benefits.ObjectiveTo investigate the treatment effects of pramipexole (PPX) sustained release (SR) versus PPX immediate release (IR) on nocturnal symptoms in advanced PD patients with sleep disturbances.Materials and methodsIn this study, the PPX clinical trial (NCT00466167) was retrospectively analyzed for PD Sleep Scale (PDSS) total and domain scores in patients with advanced idiopathic PD receiving either PPX SR or PPX IR, who experienced motor fluctuations while on stable levodopa with a baseline PDSS total score of <90, indicating sleep disturbances. Analysis of covariance test was used to compare the adjusted mean changes at week 18 from baseline between treatment groups, after adjusting for pooled country and baseline scores.ResultsA total of 119 patients with PD reported sleep disturbances at baseline (PDSS <90; SR, n=59; IR, n=60). At week 18, patients receiving PPX SR reported numerically greater improvement of sleep disturbance than those receiving PPX IR, although the difference of 6.8 points was not statistically significant (adjusted mean changes in PDSS total score, SR=28.5 versus IR=21.7 points, P=0.165). Patients receiving PPX SR observed a numerically greater adjusted mean change in all PDSS domains compared with PPX IR. The overall proportions of patients with any adverse event were similar between both PPX SR and IR groups (62.7% versus 70.0%).ConclusionBoth the PPX formulations showed improvements in nocturnal symptoms in advanced PD patients with sleep disturbances and were generally well tolerated. Given the known pharmacokinetic profile of an SR formulation and numerical advantage in PDSS mean change over IR formulation, these preliminary evidences support future prospectively designed studies to investigate the effects of PPX SR for improved sleep.

OBJECTIVES: To report effects of BG-12 on the reduction in number of relapses requiring intravenous steroids and multiple sclerosis (MS)-related hospitalizations in DEFINE and CONFIRM, two Phase 3 studies of efficacy and safety of oral BG-12 (dimethyl fumarate) in patients with relapsing-remitting MS (RRMS). METHODS: Patients aged 18 -55 years with RRMS (McDonald criteria 2005) and an Expanded Disability Status Scale score of 0 -5.0 were randomized equally to oral BG-12 240 mg twice (BID) or three times daily (TID) or placebo in DEFINE, or to oral BG-12 240 mg BID or TID, placebo, or subcutaneous glatiramer acetate 20 mg/day (reference comparator) in CONFIRM. The primary endpoint at 2 years was: the proportion of patients relapsed in DEFINE, and annualized relapse rate in CONFIRM. Tertiary endpoints in both studies included number of relapses requiring intravenous steroid therapy and MS-related hospitalizations. RESULTS: The intent-to-treat populations of the DEFINE and CONFIRM studies comprised 1,234 and 1,417 patients, respectively. In DEFINE, BG-12 reduced the adjusted annualized rate of relapses requiring steroids at 2 years by 52% (BID; rate ratio, 0.48 [95% confidence interval, 0.36 -0.63]) and 51% (TID; 0.49 [0.37-0.64]) vs placebo (both pϽ0.0001). Relative reductions in CONFIRM were 44% (BID; 0.56 [0.42-0.76]) and 49% (TID; 0.51 [0.38 -0.70]) vs placebo (pϭ0.0002 and pϽ0.0001). BG-12 also reduced the adjusted annualized rate of MS-related hospitalizations at 2 years in DEFINE by 35% (BID; 0.