Rasagiline In Patients Research Articles

Safety and effectiveness of rasagiline in patients with Parkinson’s disease in Japan: a post-marketing surveillance study

ABSTRACT Background Rasagiline is a monoamine oxidase B inhibitor for the treatment of Parkinson’s disease (PD). This study assessed the safety and effectiveness of rasagiline in patients with PD in routine clinical practice in Japan. Research design and methods This multicenter, prospective, observational study (148 sites) enrolled patients (1 November 2018−31 October 2020) with PD. Patients received rasagiline orally 1 mg once daily; maximum observation period was 24 months. The incidence of adverse drug reactions (ADRs) was evaluated; effectiveness was assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III total score. Results The safety analysis set comprised 961 patients (mean age, 72.50 years; 53.80% female; mean duration of PD, 6.82 years). Mean treatment duration was 14.74 months, with 42.25% receiving rasagiline for ≥ 19 months; 189 (19.67%) had ≥ 1 ADR. Common ADRs were dyskinesia (4.06%), orthostatic hypotension (2.29%), hallucination (1.87%), visual hallucination, nausea, fall (1.56% each), dizziness (1.35%), and somnolence (1.25%). Mean (standard deviation) UPDRS Part III total score was 28.5 (14.35) at baseline and 25.5 (14.98) at the final assessment. Conclusions No new concerns in safety and effectiveness regarding rasagiline in Japanese patients with PD were raised. Trial registration ClinicalTrials.gov: NCT03727139; Japan Pharmaceutical Information Center Clinical Trials Information: JapicCTI-184181.

Neuroprotection with rasagiline in patients with macula-off retinal detachment: A randomized controlled pilot study

We aimed to evaluate the neuroprotective efficacy of rasagiline in pseudophakic patients who had surgery for macula-off rhegmatogenous retinal detachment (RRD). This was a 6-month, prospective, randomized, double-blind, placebo-controlled pilot study. Patients presenting with acute macula-off RRD were recruited and randomized 1:1 to receive rasagiline 1 mg/day or placebo for 7 days. Best-corrected visual acuity (BCVA) and optical coherence tomography were acquired 1 day before as well as 2 days, 3 weeks, 3 months and 6 months after surgery. We screened 26 patients with RRD whereof 23 were eventually included and randomized. The primary outcome was final BCVA. Secondary outcomes included central retinal thickness (CRT) and adverse events (AE). We evaluated photoreceptor cells (prc) recovery through morphological measurements. The baseline characteristics were comparable between groups. BCVA significantly improved in both groups (letters gained: rasagiline 61.5 ± 18.1 vs placebo 55.3 ± 29.2, p = 0.56), but no significant inter-group difference was found at any visit. CRT was stable 3 weeks after surgery onwards, with no inter-group difference. No treatment-emergent AE occurred. Significant prc restoration was observed from 3 weeks to 6 months after surgery, without inter-group difference at either visit. Ellipsoid zone integrity (β = 0.517, p = 0.008) and foveal bulge (β = 0.387, p = 0.038) were significant predictors of good final BCVA. In conclusion, perioperative oral treatment with rasagiline 1 mg/day for 7 days did not show significant benefits on visual or anatomical outcomes in macula-off RRD patients.

The Effects of Rasagiline on Glucose Metabolism and Cognition and Their Relationship to Tau Burden in a Double-Blind, Placebo-Controlled Phase Ii Clinical Trial of Participants with Alzheimer's Dementia

Background: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a MAO-B inhibitor, in mild to moderate Alzheimer’s disease. The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (FDG PET) compared to placebo. Secondary objectives included use of flortaucipir PET to assess effects on tau pathology and determination of directional consistency of clinical endpoints with FDG PET. Methods: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to receive oral rasagiline or placebo (NCT02359552). FDG PET was analyzed at screening for the presence of an AD-like pattern as an inclusion criterion and longitudinally using prespecified regions of interest and image classification. Participants who completed baseline and 24-week FDG PET scans and passed quality control were included in the primary analysis; secondary clinical outcomes were analyzed using an ITT model. Findings: Between May 19, 2015 and January 26, 2018, 96 participants were screened, 50 randomized, and 43 completed treatment. The study met its primary endpoint, demonstrating favorable change in FDG PET differences in rasagiline vs. placebo in middle frontal (2·5%,95%CI 0·3–4·7%,p<0·025), anterior cingulate (2·2%,0·1–4·3%,p<0·041), and striatal (2·4%,0·2–4·3%,p<0·023) regions. Tau PET cortical region secondary endpoints did not differ between study arms. Clinical secondary endpoint measures of Quality of Life (p<0·04) and COWAT favored rasagiline. Rasagiline was generally well tolerated with low rates of both serious and other adverse events and notably less neuropsychiatric symptoms reported with rasagiine. Interpretation: These study outcomes illustrate the potential benefits of rasagiline on clinical and neuroimaging measures in AD, with positive effects on frontostriatal pathways. Strengths are the FDG PET results coupled with the directional consistency of clinical outcomes. This data adds important converging evidence for POC of rasagiline in patients well characterized using FDG and tau PET. Limitations include the study size and duration. Further investigation of rasagiline in AD is warranted. Funding: Alzheimer’s Drug Discovery Foundation (ADDF) Declaration of Interest: Dawn Matthews is an employee of ADM Diagnostics, Inc., which was compensated to provide image analysis for the study. Dr. Aaron Ritter has nothing to disclose. Dr. Ronald Thomas has nothing to disclose. Randolph Andrews is an employee of ADM Diagnostics, Inc., which was compensated to provide image analysis for the study. Dr. Ana Lukic is an employee of ADM Diagnostics, Inc., which was compensated to provide image analysis for the study. Carolyn Revta has received grants from Toyama Pharmaceuticals, Biohaven Pharmaceuticals, and Vivoryon (Probiodrug) during the conduct of the study. Dr. Babak Tousi has received a grant from the Alzheimer’s Drug Discovery Foundation during the study. Dr. James Leverenz has received research support from the Alzheimer’s Association, Avid Radiopharmaceuticals, Department of Defense, GE Healthcare, Lewy Body Dementia Association, Michael J Fox Foundation, National Institute of Health and Sanofi/Genzyme. Dr. Howard Fillit is founding Executive Director and Chief Science Officer of the Alzheimer’s Drug Discovery Foundation which funded the rasagiline clinical trial, and has provided consulting to the following pharmaceutical companies: Axovant, vTv, Lundbeck, Otsuka, Lilly, Biogen (RTI), Roche, Genentech, Merck, Samus, Pfizer, and Alector. Dr. Kate Zhong has nothing to disclose. Dr. Howard Feldman reports a service agreement through UCSD with the Cleveland Clinic for data management and biostatistics during the conduct of this study; grants from Toyama Pharmaceuticals , Biohaven Pharmaceuticals , and Vivoryon (Probiodrug). Dr. Feldman also reports service agreements through UCSD for consulting with Eisai Pharmaceuticals, Merck Pharmaceuticals, Tau RX , Samus Therapeutics, Arkuda Therapeutics, Samumed, Axon Neurosciences Roche/Genentech Pharmaceuticals for DMC and DSMB activities; Tau Consortium for Scientific Advisory Board; Novo Nordisk for Advisory Board. He reports travel expenses Samus, Samumed, Axox and Alion Pharmaceuticals and speaker fees to UCSD from World Events Forum, Optum Health, and Medscape. Dr. Jeffrey Cummings reports grants from National Institute of General Medical Sciences (NIGMS) COBRE grant #P20GM109025, during the conduct of the study; personal fees from Acadia, Actinogen, AgenBio, Alkahest, Alzheon, Avanir, Axsome, Biogen, Cassava, Cerecin, Cerevel, Cognoptix, Cortexyme, EIP, Eisai, Foresight, Green Valley, Grifols, Idorsia, Karuna, Nutricia, Orion, Otsuka, Probiodrug, QR Pharma, ReMYND, Resverlogix, Roche, Samumed, Samus Therapeutics, Third Rock, Signant Health, Sunovion, Suven, and United Neuroscience pharmaceutical and assessment companies;other from Alzheimer Drug Discovery Foundation; other from ADAMAS, BioAsis, MedAvante, QR Pharma, and United Neuroscience,;personal fees from Neuropsychiatric Inventory (NPI), outside the submitted work; and Dr. Cummings is the Chief Scientific Advisor for CNS Innovations. Ethical Approval: The study was conducted under Institutional Review Board approval.

Efficacy and tolerability of rasagiline in daily clinical use—A post marketing observational study in patients with Parkinson’s disease focusing on non-motor symptoms and QoL

Rasagiline (Azilect®) is a highly selective irreversible second generation MAO-B inhibitor indicated for the treatment of idiopathic Parkinson’s disease (PD) as monotherapy or as adjunct therapy (with levodopa). The 6-month observational study included 871 patients to investigate the efficacy and tolerability of rasagiline in clinical daily practice focussing on non-motor symptoms and quality of life.Two thirds of the patients received 1mg rasagiline daily as add-on to their regular PD-medication, the rest as monotherapy.Efficacy criteria were: (1) CURS, (2) PS-23 scale on Parkinson non-motor symptom strength, (3) UPDRS, part IV B, (4) duration of OFF-periods, (5) QoL by PDQ-8, (6) WHO-5 Well-being Index and (7) change of global clinical impression (CGI-I).Significant improvements have been observed in total severity of PD: PS-23 total score declined from 46.4 to 42.2. Health and general well-being measured by PDQ-8 improved significantly from baseline 16.3 to 14.3. Emotional well-being according to WHO-5 improved significantly from 14.4 to 16.4.Positive effects of rasagiline on motor symptoms have been observed: CURS total score improved significantly from 14.8 to 11.4. The proportion of patients without any OFF period increased from 47.1% to 59.1%. Patients reported that OFF periods decreased significantly, most pronounced the morning OFF. Rasagiline has shown to be effective either in monotherapy or in combination with l-Dopa, dopamine agonists or both.AEs were reported by 6.5% of the patients. The treatment with rasagiline in patients with PD resulted in improvements of motor and non-motor symptoms and led to an improved quality of life.

Efficacy of rasagiline in patients with Parkinson’s disease and mild cognitive impairment: results from moderato, a 24-week randomized, double-blind, placebo-controlled trial

Efficacy of rasagiline in patients with Parkinson’s disease and mild cognitive impairment: results from moderato, a 24-week randomized, double-blind, placebo-controlled trial

A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: Possible mitochondrial biomarker target engagement

Rasagiline, a monoamine oxidase B inhibitor, slowed disease progression in the SOD1 mouse, and in a case series of patients with amyotrophic lateral sclerosis (ALS). Here we determine whether rasagiline is safe and effective in ALS compared to historical placebo controls, and whether it alters mitochondrial biomarkers. We performed a prospective open-label, multicenter screening trial of 36 ALS patients treated with 2 mg oral rasagiline daily for 12 months. Outcomes included the slope of deterioration of the revised ALS Functional Rating Scale (ALSFRS-R), adverse event monitoring, time to treatment failure, and exploratory biomarkers. Participants experienced no serious drug-related adverse events, and the most common adverse event was nausea (11.1%). Rasagiline did not improve the rate of decline in the ALSFRS-R; however, differences in symptom duration compared to historical placebo controls differentially affected ALSFRS-R slope estimates. Rasagiline changed biomarkers over 12 months, such that the mitochondrial membrane potential increased (JC-1 red/green fluorescent ratio 1.92, p = 0.0001) and apoptosis markers decreased (Bcl-2/Bax ratio 0.24, p < 0.0001). In conclusion, engagement of exploratory biomarkers and questions about comparability of baseline characteristics lead us to recommend a further placebo-controlled trial.

Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial

Multiple system atrophy is a complex neurodegenerative disorder for which no effective treatment exists. We aimed to assess the effect of rasagiline on symptoms and progression of the parkinsonian variant of multiple system atrophy. We did this randomised, double-blind, placebo-controlled trial between Dec 15, 2009, and Oct 20, 2011, at 40 academic sites specialised in the care of patients with multiple systemic atrophy across 12 countries. Eligible participants aged 30 years or older with possible or probable parkinsonian variant multiple system atrophy were randomly assigned (1:1), via computer-generated block randomisation (block size of four), to receive either rasagiline 1 mg per day or placebo. Randomisation was stratified by study centre. The investigators, study funder, and personnel involved in patient assessment, monitoring, analysis and data management were masked to group assignment. The primary endpoint was change from baseline to study end in total Unified Multiple System Atrophy Rating Scale (UMSARS) score (parts I and II). Analysis was by modified intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00977665. We randomly assigned 174 participants to the rasagiline group (n=84) or the placebo group (n=90); 21 (25%) patients in the rasagiline group and 15 (17%) in the placebo group withdrew from the study early. At week 48, patients in the rasagiline group had progressed by an adjusted mean of 7·2 (SE 1·2) total UMSARS units versus 7·8 (1·1) units in those in the placebo group. This treatment difference of -0·60 (95% CI -3·68 to 2·47; p=0·70) was not significant. 68 (81%) patients in the rasagiline group and 67 (74%) patients in the placebo group reported adverse events, and we recorded serious adverse events in 29 (35%) versus 23 (26%) patients. The most common adverse events in the rasagiline group were dizziness (n=10 [12%]), peripheral oedema (n=9 [11%]), urinary tract infections (n=9 [11%]), and orthostatic hypotension (n=8 [10%]). In this population of patients with the parkinsonian variant of multiple system atrophy, treatment with rasagiline 1 mg per day did not show a significant benefit as assessed by UMSARS. The study confirms the sensitivity of clinical outcomes for multiple system atrophy to detect clinically significant decline, even in individuals with early disease. Teva Pharmaceutical Industries and H Lundbeck A/S.

Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson’s disease

Neuroprotective therapy has been proposed for age-related neurodegenerative disorders, including Parkinson’s disease. Inhibitors of type B monoamine oxidase (MAOB-Is), rasagiline and (-)deprenyl, are the most promising candidate neuroprotective drugs. Clinical trials of rasagiline in patients with Parkinson’s disease suggest that rasagiline may have some disease-modifying effects. Results using animal and cellular models have proved that the MAOB-Is protect neurons by the intervention of ‘intrinsic’ mitochondrial apoptotic cascade and the induction of prosurvival antiapoptotic Bcl-2 and neurotrophic factors. Rasagiline-related MAOB-Is prevent mitochondrial permeability transition induced by various insults and activation of subsequent apoptotic cascades: cytochrome c release, casapase activation, and condensation and fragmentation of nuclear DNA. MAOB-Is increase transcription of prosurvival genes through activating the nuclear transcription factor-(NF) system. Rasagiline increases the protein and mRNA levels of GDNF in dopaminergic SH-SY5Y cells, whereas (-)deprenyl increases those of BDNF. Systemic administration of (-)deprenyl and rasagiline increases these neurotrophic factors in the cerebrospinal fluid from patients with Parkinson’s disease and nonhuman primates. This review presents recent advances in our understanding of the neuroprotection offered by MAOB-Is and possible evaluation of neuroprotective efficacy in clinical samples is discussed.

Kombinationstherapie mit Rasagilin: Verbesserung der Lebensqualität und motorischen Fluktuationen bei Parkinson-Patienten

Rasagiline (Azilect®) is a potent, highly selective, irreversible second generation MAO-B inhibitor and is indicated for treatment of idiopathic Parkinson's disease (iPD) as monotherapy (without levodopa) or adjunct therapy (with levodopa). The present 4-month observational study included 754 patients with iPD to investigate efficacy and tolerability of rasagiline in clinical daily practice. The focus was on rasagiline's effects on motor fluctuations and quality of life (QoL) as add-on therapy. 545 patients received 1 mg rasagiline daily as add-on to their regular PD medication. Efficacy criteria were: 1. Columbia University Rating Scale (CURS), 2. clinical fluctuations subscale of the Unified Parkinson's Disease Rating Scale (UPDRS, part IV B), 3.) duration of OffF periods documented in 24-h home diaries, 4. QoL was assessed by Parkinson's Disease Questionnaire (PDQ-39). In 86.6 % of the cases PD medication remained unchanged. Rasagiline was most frequently co-administered with levodopa / DCI (81.7 %) and / or dopamine agonists (65.8 %). The CURS total score improved by 22 %. The improvement rates in CURS items ranged between 31.1 % to 48.4 %. 39 % of the patients experienced a reduction in Off time during the waking period. The duration of Off periods decreased from 120 to 45 minutes. In all aspects of PDQ-39, an improvement in QoL was documented. The total score improved significantly by 7.3 points (20.1 %). Adverse events were reported by 8.4 % of the patients. The add-on medication of rasagiline in patients with iPD resulted in improvements of motor fluctuations and led to an improved quality of life in the self-estimation of the patients.