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Adjunct rasagiline to treat Parkinson's disease with motor fluctuations: a randomized, double-blind study in China.

ABSTRACT: The use of adjunct rasagiline in levodopa-treated patients with Parkinson's disease and motor fluctuations is supported by findings from large-scale clinical studies. This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson's disease, as a product registration study.This 16-week, randomized, double-blind, parallel-group, multicenter, placebo-controlled study of rasagiline 1 mg/day included levodopa-treated patients with Parkinson's disease and motor fluctuations. The primary efficacy endpoint was mean change from baseline in total daily OFF time over 16 weeks. Secondary endpoints were Clinical Global Impressions - Improvement (CGI-I), and change in Unified Parkinson's Disease Rating Scale (UPDRS) Activities of daily living (ADL) and Motor scores. Patient well-being (EQ-5D), and the frequency of adverse events were also assessed.In total, 324 levodopa-treated patients were randomized to rasagiline 1 mg/day (n?=?165) or placebo (n?=?159). Over 16 weeks, rasagiline statistically significantly reduced the mean [95% confidence interval] total daily OFF time versus placebo (-?0.5 h [-?0.92, -?0.07]; p?=?0.023). There were also statistically significant improvements versus placebo in CGI-I (-?0.4 points [-?0.61, -?0.22]; p?

SUBMITTER: Zhang Z

PROVIDER: S-EPMC6026338 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Adjunct rasagiline to treat Parkinson's disease with motor fluctuations: a randomized, double-blind study in China.

Zhang Zhenxin Z Shao Ming M Chen Shengdi S Liu Chunfeng C Peng Rong R Li Yansheng Y Wang Jian J Zhu Suiqiang S Qu Qiumin Q Zhang Xiaoying X Chen Haibo H Sun Xiangru X Wang Yanping Y Sun Shenggang S Zhang Baorong B Li Jimei J Pan Xiaoping X Zhao Gang G

Translational neurodegeneration 20180630

<h4>Background</h4>The use of adjunct rasagiline in levodopa-treated patients with Parkinson's disease and motor fluctuations is supported by findings from large-scale clinical studies. This study is to investigate the efficacy and safety of adjunct rasagiline in Chinese patients with Parkinson's disease, as a product registration study.<h4>Methods</h4>This 16-week, randomized, double-blind, parallel-group, multicenter, placebo-controlled study of rasagiline 1 mg/day included levodopa-treated pa ...[more]

PMID: 29988514

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Project description:BackgroundRasagiline is a monoamine oxidase-B inhibitor used for Parkinson's disease (PD) treatment, but its effectiveness on Chinese patients is unclear. This study aimed to evaluate the efficacy and safety of rasagiline monotherapy in Chinese patients with early PD.MethodsA 26-weeks, randomized, double-blind, placebo-controlled study has been performed at 15 sites in China and enrolled outpatients (≥35 years old) with idiopathic PD without a history of using any dopaminergic drugs. Participants were randomized 1:1 to receive rasagiline 1 mg once daily or placebo. The primary endpoint was the change of the Unified Parkinson's Disease Rating Scale (UPDRS) total score from baseline to 26 weeks treatment. Secondary endpoints included changes in UPDRS subscale scores from part I to III. Health status was assessed with the PD Questionnaire (PDQ)-39 and EuroQol-Five-Dimension (EQ-5D) questionnaire. Safety profile was collected until 30 weeks after randomization.ResultsA total of 130 patients (n = 65/group) were recruited, and 127 (rasagiline, n = 64; placebo, n = 63) were included in the full analysis set. Baseline characteristics were comparable between the two groups. The decrease in the mean UPDRS total score was greater in the rasagiline group than in the placebo group (- 3.18 ± 0.95 vs. - 0.18 ± 0.98, P = 0.025), and the mean UPDRS part I non-motor symptoms score (- 0.54 ± 0.15 vs. -0.08 ± 0.15, P = 0.003) were significantly decreased in the rasagiline group compared with placebo treated patients. An improvement trend was observed in the active treatment group for the subscales evaluation with parts II and III, while the difference to placebo was not statistically significant. Life quality assessed by the EQ-5D visual analog scale improved in the rasagiline group but worsened in placebo treated patients. The overall incidence of treatment-emergent adverse events (AEs) was slightly lower in the rasagiline group (41.5%) than in the placebo group (46.2%).ConclusionsRasagiline is effective, safe, and well tolerated as monotherapy for the treatment of Chinese PD patients.Trial registrationClinicaltrials.gov: NCT01556165. Registered 13 Mar 2012.

Project description:Background: Movement fluctuations are the main complication of Parkinson's disease (PD) patients receiving long-term levodopa (L-dopa) treatment. We compared and ranked the efficacy and safety of dopamine agonists (DAs) with regard to motor fluctuations by using a Bayesian network meta-analysis (NMA) to quantify information from randomized controlled trials (RCTs). Methods and Findings: We carried out a systematic review and meta-analysis, and only RCTs comparing DAs for advanced PD were included. Electronic databases (PubMed, Embase, and Cochrane Library) were systematically searched for relevant studies published until January 2021. Two reviewers independently extracted individual study data and evaluated studies for risk of bias using the Cochrane Risk of Bias tool. Network meta-analyses using a Bayesian framework were used to calculate the related parameters. The pre-specified primary and secondary outcomes were efficacy ("ON" time without troublesome dyskinesia, "OFF" time, "ON" time, "UPDRS-III," and "UPDRS-II") and safety [treatment-emergent adverse events (TEAE) and other adverse events] of DAs. The results are presented as the surface under the cumulative ranking (SUCRA) curve. A total of 20 RCTs assessing 6,560 patients were included. The general DA effects were ranked from high to low with respect to the amount of "ON" time without troublesome dyskinesia as follows: apomorphine (SUCRA = 97.08%), pramipexole_IR (probability = 79.00%), and ropinirole_PR (SUCRA = 63.92%). The general safety of DAs was ranked from high to low with respect to TEAE as follows: placebo (SUCRA = 74.49%), pramipexole_ER (SUCRA = 63.6%), sumanirole (SUCRA = 54.07%), and rotigotine (SUCRA = 53.84%). Conclusions: This network meta-analysis shows that apomorphine increased "ON" time without troublesome dyskinesia and decreased "OF" time for advanced PD patients. The addition of pramipexole, ropinirole, or rotigotine to levodopa treatment in advanced PD patients with motor fluctuations increased "ON" time without troublesome dyskinesia, improved the UPDRS III scores, and ultimately ameliorated the UPDRS II scores, thereby maximizing its benefit. This NMA of pramipexole, ropinirole, and rotigotine represents an effective treatment option and has an acceptable safety profile in patients with advanced PD.

Project description:Background Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease and as an adjunct therapy to levodopa in Parkinson's disease with motor fluctuations. Objectives This meta-analysis aimed to provide updated evidence on the efficacy for motor and nonmotor symptoms and the safety of rasagiline/levodopa versus levodopa in patients with Parkinson's disease experiencing motor fluctuations. Methods A systematic literature search was conducted (January 18-19, 2021) using PubMed, Cochrane Library, EMBASE, Web of Science, and Google Scholar to identify randomized controlled trials comparing rasagiline/levodopa versus placebo/levodopa in patients with Parkinson's disease experiencing motor fluctuations. Outcomes included change in wearing-off time, Unified Parkinson's Disease Rating Scale (UPDRS)/Movement Disorder Society-UPDRS (MDS-UPDRS) II and III scores, treatment-emergent adverse events (TEAEs), and Parkinson's Disease Questionnaire (PDQ-39) summary index score. A random effect model was used to estimate the treatment effects. Results Six studies were included (1912 patients). Significant improvements in wearing-off time (standardized mean difference [SMD]: −0.50, 95% confidence interval [CI]: –0.92 to –0.09, p = 0.002), levodopa dosage (SMD: −0.18, 95% CI: −0.35 to –0.01, p = 0.041), UPDRS/MDS-UPDRS II (SMD: −0.39, 95% CI: −0.52 to –0.25, p < 0.0001), UPDRS/MDS-UPDRS III (SMD: −0.30, 95% CI: −0.44 to –0.16, p < 0.0001), and PDQ-39 summary index score (SMD: –0.21, 95% CI: –0.37 to –0.04, p = 0.013) were observed with rasagiline/levodopa versus placebo/levodopa. The incidence of TEAEs did not differ between treatments (risk ratio: 1.13, 95% CI: 0.98–1.30, p = 0.093). Conclusions This meta-analysis further indicated the superiority of rasagiline/levodopa in improving motor and nonmotor symptoms of Parkinson's disease, with a similar safety profile to that of levodopa in Parkinson's disease with motor fluctuations.

Project description:ObjectiveIn the absence of controlled trials, treatment of neonatal seizures has changed minimally despite poor drug efficacy. We tested bumetanide added to phenobarbital to treat neonatal seizures in the first trial to include a standard-therapy control group.MethodsA randomized, double-blind, dose-escalation design was employed. Neonates with postmenstrual age 33 to 44 weeks at risk of or with seizures were eligible. Subjects with electroencephalography (EEG)-confirmed seizures after ≥20 and <40mg/kg phenobarbital were randomized to receive additional phenobarbital with either placebo (control) or 0.1, 0.2, or 0.3mg/kg bumetanide (treatment). Continuous EEG monitoring data from ≥2 hours before to ≥48 hours after study drug administration (SDA) were analyzed for seizures.ResultsSubjects were randomized to treatment (n = 27) and control (n = 16) groups. Pharmacokinetics were highly variable among subjects and altered by hypothermia. The only statistically significant adverse event was diuresis in treated subjects (48% vs 13%, p = 0.02). One treated (4%) and 3 control subjects died (19%, p = 0.14). Among survivors, 2 of 26 treated subjects (8%) and 0 of 13 control subjects had hearing impairment, as did 1 nonrandomized subject. Total seizure burden varied widely, with much higher seizure burden in treatment versus control groups (median = 3.1 vs 1.2 min/h, p = 0.006). There was significantly greater reduction in seizure burden 0 to 4 hours and 2 to 4 hours post-SDA (both p < 0.01) compared with 2-hour baseline in treatment versus control groups with adjustment for seizure burden.InterpretationAlthough definitive proof of efficacy awaits an appropriately powered phase 3 trial, this randomized, controlled, multicenter trial demonstrated an additional reduction in seizure burden attributable to bumetanide over phenobarbital without increased serious adverse effects. Future trials of bumetanide and other drugs should include a control group and balance seizure severity. ANN NEUROL 2021;89:327-340.

Dataset Information

Adjunct rasagiline to treat Parkinson's disease with motor fluctuations: a randomized, double-blind study in China.

Publications

Adjunct rasagiline to treat Parkinson's disease with motor fluctuations: a randomized, double-blind study in China.

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