Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in Patients With Parkinson's Disease and a GBA Mutation: Results From Part 1 of the Randomised, Double-Blinded, Placebo-Controlled MOVES-PD Trial

2021 ◽  
Author(s):  
Judith Peterschmitt ◽  
Hidemoto Saiki ◽  
Taku Hatano ◽  
Thomas Gasser ◽  
Stuart H. Isaacson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Double Blinded

scholarly journals Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in Patients with Parkinson’s Disease and a GBA Mutation: Results from Part 1 of the Randomized, Double-Blinded, Placebo-Controlled MOVES-PD Trial

2021 ◽  
pp. 1-14
Author(s):  
M. Judith Peterschmitt ◽  
Hidemoto Saiki ◽  
Taku Hatano ◽  
Thomas Gasser ◽  
Stuart H. Isaacson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Japanese Patients ◽  
Dependent Manner ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dose Escalation Study ◽  
Synthase Inhibitor ◽  
Double Blinded ◽  
Favorable Safety ◽  
Gba Mutations

Background: Glucocerebrosidase gene (GBA) mutations influence risk and prognosis of Parkinson’s disease (PD), possibly through accumulation of glycosphingolipids, including glucosylceramide (GL-1). Venglustat is a novel, brain penetrant glucosylceramide synthase inhibitor. Objective: Evaluate venglustat pharmacology, safety, and tolerability in patients with PD and GBA mutations (GBA-PD). Methods: Part 1 of the phase 2 MOVES-PD trial (NCT02906020) was a randomized, double-blinded, placebo-controlled, dose-escalation study performed in six countries. Eligible participants included Japanese and non-Japanese patients aged 18–80 years with PD diagnosis and heterozygous GBA mutation. Participants were randomized to three doses of once-daily oral venglustat or placebo and were followed up to 36 weeks (Japanese participants: 52 weeks). Primary endpoint was venglustat safety and tolerability versus placebo. Secondary and exploratory endpoints included venglustat pharmacokinetics and pharmacodynamics. Results: Participants (N = 29) received venglustat (Japanese, n = 9; non-Japanese, n = 13) or placebo (n = 3; n = 4). Eight (89%) Japanese and 12 (92%) non-Japanese venglustat-treated participants experienced at least one adverse event (AE) versus two (67%) and four (100%) participants from the respective placebo groups. Most AEs were mild or moderate; no serious AEs or deaths occurred. Two venglustat-treated non-Japanese participants discontinued due to AEs (confusional state and panic attack). Over 4 weeks, venglustat exposure in plasma and cerebrospinal fluid (CSF) increased, and GL-1 levels in plasma and CSF decreased, both in a dose-dependent manner. At the highest dose, CSF GL-1 decreased by 72.0% in Japanese and 74.3% in non-Japanese participants. Conclusion: Venglustat showed favorable safety and tolerability in MOVES-PD Part 1 and target engagement was achieved in CSF.

scholarly journals Boxing vs Sensory Exercise for Parkinson’s Disease: A Double-Blinded Randomized Controlled Trial

2021 ◽  
pp. 154596832110231
Author(s):  
Kishoree Sangarapillai ◽  
Benjamin M. Norman ◽  
Quincy J. Almeida
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Controlled Trial ◽  
Repeated Measures ◽  
Rating Scale ◽  
Controlled Trial ◽  
Motor Symptoms ◽  
Post Intervention ◽  
Randomized Controlled ◽  
Double Blinded

Background. Exercise is increasingly becoming recognized as an important adjunct to medications in the clinical management of Parkinson’s disease (PD). Boxing and sensory exercise have shown immediate benefits, but whether they continue beyond program completion is unknown. This study aimed to investigate the effects of boxing and sensory training on motor symptoms of PD, and whether these benefits remain upon completion of the intervention. Methods. In this 20-week double-blinded randomized controlled trial, 40 participants with idiopathic PD were randomized into 2 treatment groups, (n = 20) boxing or (n = 20) sensory exercise. Participants completed 10 weeks of intervention. Motor symptoms were assessed at (week 0, 10, and 20) using the Unified Parkinson’s Disease Rating Scale (UPDRS-III). Data were analyzed using SPSS, and repeated-measures ANOVA was conducted. Results. A significant interaction effect between groups and time were observed F(1, 39) = 4.566, P = .036, where the sensory group improved in comparison to the boxing group. Post hoc analysis revealed that in comparison to boxing, the effects of exercise did not wear off at washout (week 20) P < .006. Conclusion. Future rehabilitation research should incorporate similar measures to explore whether effects of exercise wear off post intervention.

scholarly journals Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson’s disease

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Antonio Martin-Bastida ◽  
Roberta J. Ward ◽  
Rexford Newbould ◽  
Paola Piccini ◽  
David Sharp ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Clinical Trial ◽  
Parkinson's Disease ◽  
Iron Chelation ◽  
Controlled Clinical Trial ◽  
Phase 2 ◽  
Brain Iron ◽  
Double Blinded

scholarly journals Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease

2019 ◽  
Vol 7 (2) ◽  
pp. e00470 ◽  
Author(s):  
Fernando L. Pagan ◽  
Michaeline L. Hebron ◽  
Barbara Wilmarth ◽  
Yasar Torres‐Yaghi ◽  
Abigail Lawler ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Dose ◽  
Pharmacokinetics And Pharmacodynamics

Effects of acute cannabidiol administration on anxiety and tremors induced by a Simulated Public Speaking Test in patients with Parkinson’s disease

2020 ◽  
Vol 34 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Stephanie Martins de Faria ◽  
Daiene de Morais Fabrício ◽  
Vitor Tumas ◽  
Paula Costa Castro ◽  
Moacir Antonelli Ponti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Repeated Measures ◽  
Public Speaking ◽  
Cannabis Sativa ◽  
Signs And Symptoms ◽  
Systemic Blood Pressure ◽  
Speaking Test ◽  
Double Blinded ◽  
Simulated Public Speaking

Background: Cannabidiol (CBD) is one of the main components of Cannabis sativa and has anxiolytic properties, but no study has been conducted to evaluate the effects of CBD on anxiety signs and symptoms in patients with Parkinson’s disease (PD). This study aimed to evaluate the impacts of acute CBD administration at a dose of 300 mg on anxiety measures and tremors induced by a Simulated Public Speaking Test (SPST) in individuals with PD. Methods: A randomised, double-blinded, placebo-controlled, crossover clinical trial was conducted. A total of 24 individuals with PD were included and underwent two experimental sessions within a 15-day interval. After taking CBD or a placebo, participants underwent the SPST. During the test, the following data were collected: heart rate, systemic blood pressure and tremor frequency and amplitude. In addition, the Visual Analog Mood Scales (VAMS) and Self-Statements during Public Speaking Scale were applied. Statistical analysis was performed by repeated-measures analysis of variance (ANOVA) while considering the drug, SPST phase and interactions between these variables. Results: There were statistically significant differences in the VAMS anxiety factor for the drug; CBD attenuated the anxiety experimentally induced by the SPST. Repeated-measures ANOVA showed significant differences in the drug for the variable related to tremor amplitude as recorded by the accelerometer. Conclusion: Acute CBD administration at a dose of 300 mg decreased anxiety in patients with PD, and there was also decreased tremor amplitude in an anxiogenic situation.

scholarly journals Combined Metabolic Activators Improve Cognitive Functions without Altering Motor Scores in Parkinson's Disease

2021 ◽  
Author(s):  
BURAK YULUG ◽  
OZLEM ALTAY ◽  
XIANGYU LI ◽  
LUTFU HANOGLU ◽  
SEYDA CANKAYA ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Placebo Group ◽  
Cognitive Functions ◽  
Plasma Proteins ◽  
Metabolic Abnormalities ◽  
Phase 2 ◽  
Nicotinamide Riboside ◽  
Phase 2 Study ◽  
Double Blinded

The neuropathologic hallmarks of Parkinson's disease (PD) are associated with mitochondrial dysfunction and metabolic abnormalities. We have reported that the Combined Metabolic Activators (CMA), consisting of L-serine, nicotinamide riboside, N-acetyl-L-cysteine, and L-carnitine tartrate can be used in treating metabolic abnormalities. These metabolic activators are the precursors of nicotinamide adenine dinucleotide (NAD+) and glutathione (GSH) and used in activation of mitochondrial and global metabolism. We have performed a placebo-controlled, phase-2 study in Alzheimer's disease (AD) patients and reported that the cognitive functions in AD patients is significantly improved 29% in the CMA group whereas it is improved only 14% in the placebo group after 84 days of CMA administration. Here, we designed a randomized, double-blinded, placebo-controlled, phase-2 study in PD patients with CMA administration. We found that the cognitive functions in PD patients is significantly improved 21% in the CMA group, whereas it is improved only 11% in the placebo group after 84 days of CMA administration. We also found that the administration of CMA did not affect motor functions in PD patients. We performed a comprehensive multi-omics analysis of plasma proteins and metabolites, and revealed the molecular mechanism associated with the treatment of the patients. In conclusion, our results show that treating PD patients with CMAs leads to enhanced cognitive function, as recently reported in AD patients.

Meta-analysis of Placebo-controlled Clinical Trials of Safinamide and Entacapone as Add-on Therapy to Levodopa in the Treatment of Parkinson’s Disease

2015 ◽  
Vol 10 (01) ◽  
pp. 15 ◽  
Author(s):  
Jörg Schnitker ◽  
Thomas Müller ◽  
◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Rating Scale ◽  
Meta Analysis ◽  
Search Term ◽  
Motor Complications ◽  
Controlled Clinical Trials ◽  
Total Incidence ◽  
Double Blinded

Chronic levodopa (L-dopa) treatment of Parkinson’s disease (PD) patients is sooner or later associated with the onset of motor complications, for example wearing off and dyskinesia. PD patients with motor complications usually require the addition of further PD drugs to reduce these L-dopa side effects and enhance its efficacy. Entacapone is an available catechol-O-methyltransferase (COMT) inhibitor, which was extensively investigated as add-on to L-dopa/dopadecarboxylase inhibitor (DDCI) application in PD patients. Safinamide, a watersoluble, orally active a-aminoamide derivative, which modulates dopaminergic and glutamatergic neurotransmission with a unique dual mechanism of action, has been studied in two placebo-controlled clinical trials as add-on therapy to L-dopa in fluctuating PD patients. To date, there are no head-to-head clinical trials comparing the efficacy of safinamide and entacapone in the clinic. The aim of this meta-analysis was to determine effect sizes of safinamide and entacapone as add-on treatment to L-dopa in fluctuating PD patients. A systematic search of the literature on entacapone trials up to the end of September 2014 was first conducted on the MEDLINE and EMBASE databases in order to identify appropriate studies. Definition criteria for inclusion were prospective, randomised, placebocontrolled and double-blinded trials on the efficacy and safety of entacapone or safinamide in fluctuating L-dopa-treated PD patients. Four studies for entacapone and two trials on safinamide were considered. Data from the safinamide trials were provided by Zambon and therefore ‘safinamide’ was not used as a search term. Safinamide and entacapone treatment was comparable in terms of the main efficacy variables (offtime, percentageontime, Unified Parkinson’s Disease Rating Scale). Significant advantages in favour of safinamide were shown in terms of the total incidence of adverse events (AEs) in comparison to placebo, the study discontinuation due to AEs and deaths and in the risk differences of the AEs versus placebo, particularly for nausea, vomiting, diarrhoea, dizziness, urine abnormality and shortness of breath. The odds ratio (OR) of 0.907 for any AE corresponds to an overall AE rate of 68.7 % for safinamide whereas the OR of 2.089 to an overall AE rate of 84.4 % for entacapone.

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