Opicapone for Parkinson’s disease: clinical evidence and future perspectives

2021 ◽  
Author(s):  
Clémence Leung ◽  
Olivier Rascol ◽  
Margherita Fabbri
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Evidence ◽  
Open Label ◽  
Once Daily ◽  
Beneficial Effects ◽  
Long Acting ◽  
Post Hoc ◽  
Disease Stages ◽  
Off Time

Since 2016, opicapone (OPC), a potent third-generation, long-acting, once-daily, peripheral catechol-O-methyltransferase inhibitor, is approved as add-on to levodopa in Parkinson’s disease patients with motor fluctuations. OPC 50 mg has showed to be able in reducing OFF time by an average of about 60 min daily compared with placebo, to further reduce OFF-time of about 39 min, when switched from ENT to OPC and to be safe. These beneficial effects of OPC were maintained for 1 year. Recently, several post hoc analysis and few pilot observational open-label studies, have suggested its efficacy and wider applicability for different phenotypes of motor complications and for Parkinson’s disease stages. Here we review OPC applicability and perspectives, in the light of the more recently published analysis.

GOCOVRI® (amantadine) extended-release capsules in Parkinson's disease

2021 ◽  
Author(s):  
Thomas Müller
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Extended Release ◽  
Motor Behavior ◽  
Brain Delivery ◽  
Antiviral Compound ◽  
Once Daily ◽  
Beneficial Effects ◽  
Central Monoamine ◽  
Preventive Effects

Amantadine is an old, antiviral compound, which moderately improves motor behavior in Parkinson's disease. Its current resurgence results from an innovative, delayed uptake and extended release amantadine hydrochloride capsule, given at bedtime once daily. It is the only approved compound for reduction of involuntary movements, so called dyskinesia, in fluctuating orally levodopa treated patients. It additionally ameliorates ‘off’-intervals characterized by impaired motor behavior. These beneficial effects result from higher and more continuous brain delivery of amantadine. Future clinical research is warranted on preventive effects of this amantadine capsule combined with enzyme blockers of central monoamine oxidase B and peripheral catechol-O-methyltransferase on motor complications in orally levodopa treated patients, as all these pharmacological principles support the concept of continuous dopamine substitution.

scholarly journals Continuous Subcutaneous Levodopa Delivery for Parkinson’s Disease: A Randomized Study

2020 ◽  
pp. 1-10
Author(s):  
C. Warren Olanow ◽  
Alberto J. Espay ◽  
Fabrizio Stocchi ◽  
Aaron L. Ellenbogen ◽  
Mika Leinonen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Study ◽  
Preliminary Evidence ◽  
Common Adverse Event ◽  
Open Label ◽  
Open Label Study ◽  
Dosing Regimens ◽  
Optimized Treatment ◽  
Off Time

Background: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system in development for patients with Parkinson’s disease (PD) experiencing motor fluctuations Objective: Evaluate the efficacy and safety of two ND0612 dosing regimens in patients with PD. Methods: This was a 28-day open-label study (NCT02577523) in PD patients with ≥2.5 hours/day of OFF time despite optimized treatment. Patients were randomized to treatment with either a 24-hour infusion (levodopa/carbidopa dose of 720/90 mg) or a 14-hour ‘waking-day’ infusion (levodopa/carbidopa dose of 538/68 mg plus a morning oral dose of 150/15 mg). In-clinic assessments of OFF time (primary endpoint) and ON time with or without dyskinesia were determined by a blinded rater over 8 hours (normalized to 16 hours). Results: A total of 38 patients were randomized and 33 (87% ) completed the study. Compared to baseline, OFF time for the overall population was reduced by a least squares (LS) mean[95% CI] of 2.0[– 3.3, – 0.7] hours (p = 0.003). ON time with no/mild dyskinesia was increased from baseline by a LS mean of 3.3[2.0, 4.6] hours (p <  0.0001), and ON time with moderate/severe dyskinesia was reduced by a LS mean of 1.2[– 1.8, – 0.5] hours (p≤0.001). Reduction in OFF time was larger in the 24-hour group (– 2.8[– 4.6, – 0.9] hours; p = 0.004) than in the 14-hour group (– 1.3[– 3.1, 0.5] hours; p = 0.16). Complete resolution of OFF time was observed in 42% (n = 8) of patients in the 24-hour group. Infusion site reactions were the most common adverse event. Conclusion: This study demonstrates the feasibility and safety of continuous subcutaneous delivery of levodopa as a treatment for PD and provides preliminary evidence of efficacy.

scholarly journals Levodopa-carbidopa enteral suspension in advanced Parkinson’s disease: clinical evidence and experience

2016 ◽  
Vol 10 (3) ◽  
pp. 171-187 ◽  
Author(s):  
Johan Virhammar ◽  
Dag Nyholm
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Evidence ◽  
Motor Fluctuations ◽  
Small Scale ◽  
Double Blind Study ◽  
Open Label ◽  
Double Blind ◽  
Duration Of Action ◽  
Substantial Impact

The duration of action of oral levodopa becomes shorter as Parkinson’s disease (PD) progresses. Patients with advanced PD may develop potentially disabling motor fluctuations and abnormal involuntary movement (dyskinesia), which cannot be managed with optimized oral or transdermal PD medications. The progressively worsening symptoms can have a substantial impact on the patient quality of life (QoL). Levodopa–carbidopa intestinal gel (LCIG) is delivered continuously via a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J). LCIG is licensed for the treatment of levodopa-responsive advanced PD in individuals experiencing severe motor fluctuations and dyskinesia when available combinations of antiparkinsonian medications have not given satisfactory results. Initial evidence for the efficacy and tolerability of LCIG came from a number of small-scale studies, but recently, three prospective studies have provided higher quality evidence. A 12-week double-blind comparison of LCIG with standard levodopa therapy, a 52-week open-label study extension of the double-blind study, and a 54-week open-label safety study, demonstrated significant improvements in ‘off’ time and ‘on’ time without troublesome dyskinesia, and QoL measures that were maintained in the longer term. There are also observations that LCIG may be effective treatment for nonmotor symptoms (NMS) although the evidence is limited. There is a need for further research on the efficacy of LCIG in reducing NMS, dyskinesia and improving QoL. This review surveys the clinical evidence for the effectiveness and tolerability of LCIG in the management of advanced PD and highlights some practical considerations to help optimize treatment.

scholarly journals Twice-Daily versus Once-Daily Pramipexole Extended Release Dosage Regimens in Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Ji Young Yun ◽  
Young Eun Kim ◽  
Hui-Jun Yang ◽  
Han-Joon Kim ◽  
Beomseok Jeon
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Extended Release ◽  
Daily Regimen ◽  
Open Label ◽  
Multiple Dosing ◽  
Once Daily ◽  
Open Label Study ◽  
Dopamine Agonist Therapy ◽  
Second Period

This open-label study aimed to compare once-daily and twice-daily pramipexole extended release (PER) treatment in Parkinson’s disease (PD). PD patients on dopamine agonist therapy, but with unsatisfactory control, were enrolled. Existing agonist doses were switched into equivalent PER doses. Subjects were consecutively enrolled into either once-daily-first or twice-daily-first groups and received the prescribed amount in one or two, respectively, daily doses for 8 weeks. For the second period, subjects switched regimens in a crossover manner. The forty-four patients completed a questionnaire requesting preference during their last visit. We measured the UPDRS-III, Hoehn and Yahr stages (H&Y) in medication-on state, Parkinson’s disease sleep scale (PDSS), and Epworth Sleepiness Scale. Eighteen patients preferred a twice-daily regimen, 12 preferred a once-daily regimen, and 14 had no preference. After the trial, 14 subjects wanted to be on a once-daily regimen, 25 chose a twice-daily regimen, and 5 wanted to maintain the prestudy regimen. Main reasons for choosing the twice-daily regimen were decreased off-duration, more tolerable off-symptoms, and psychological stability. The mean UPDRS-III, H&Y, and PDSS were not different. Daytime sleepiness was significantly high in the once-daily regimen, whereas nocturnal hallucinations were more common in the twice-daily. Multiple dosing should be considered if once-daily dosing is unsatisfactory. This study is registered asNCT01515774at ClinicalTrials.gov.

scholarly journals The Added Benefit of Opicapone When Used Early in Parkinson's Disease Patients With Levodopa-Induced Motor Fluctuations: A Post-hoc Analysis of BIPARK-I and -II

2021 ◽  
Vol 12 ◽  
Author(s):  
José-Francisco Rocha ◽  
Georg Ebersbach ◽  
Andrew Lees ◽  
Eduardo Tolosa ◽  
Joaquim J. Ferreira ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Wide Spectrum ◽  
Motor Fluctuation ◽  
Motor Fluctuations ◽  
Disease Course ◽  
Treatment Pathway ◽  
Levodopa Treatment ◽  
Post Hoc ◽  
Off Time

Introduction: Opicapone (OPC) was efficacious in reducing OFF-time in two pivotal trials in patients with Parkinson's disease (PD) and end-of-dose motor fluctuations (BIPARK-I and -II). Post-hoc analyses of these trials evaluated the efficacy of OPC following pre-defined segmentation of the wide spectrum of motor fluctuations in PD.Methods: Data from matching treatment arms in BIPARK-I and -II were combined for the placebo (PLC) and OPC 50-mg groups, and exploratory post-hoc analyses were performed to investigate the efficacy of OPC 50 mg vs. PLC in subgroups of patients who were in “earlier” vs. “later” stages of both their disease course (e.g., duration of PD &lt;6 years vs. ≥6 years) and levodopa treatment pathway (e.g., number of daily levodopa intakes &lt;4 vs. ≥4). Efficacy variables included changes from baseline in absolute OFF-time and total ON-time.Results: The Full Analysis Set included 517 patients (PLC, n = 255; OPC 50 mg, n = 262). OPC 50 mg was significantly more effective than PLC in reducing OFF-time and increasing ON-time in the majority of subgroup analyses (p &lt; 0.05). Moreover, patients in “earlier” stages of both their disease course and levodopa treatment pathway experienced numerically greater efficacy when using OPC 50 mg, in comparison with those in “later” stages.Conclusion: OPC 50 mg was efficacious over the whole trajectory of motor fluctuation evolution in PD patients. There was also a signal for enhanced efficacy in patients who were earlier vs. later in their disease course and levodopa treatment pathway.

scholarly journals Blinded SAPS-PD Assessment After 10 Weeks of Pimavanserin Treatment for Parkinson’s Disease Psychosis

2020 ◽  
Vol 10 (4) ◽  
pp. 1389-1396
Author(s):  
Stuart H. Isaacson ◽  
Bruce Coate ◽  
James Norton ◽  
Srdjan Stankovic
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Controlled Trial ◽  
Previous Treatment ◽  
Open Label ◽  
Beneficial Effects ◽  
The Core ◽  
Open Label Extension ◽  
Core Study ◽  
Burden Scale

Background: Parkinson’s disease psychosis (PDP) is a common nonmotor symptom that affects up to 60% of patients. Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, is approved for treating hallucinations and delusions associated with PDP. Objective: Evaluate the efficacy and tolerability of pimavanserin in an open-label extension (OLE) study. Methods: Patients completing a pivotal 6-week placebo-controlled trial (Core Study) could enroll in the OLE. All patients pimavanserin 34 mg once daily, blinded to previous treatment allocation. Prespecified blinded assessments at Week 4 were the Scale for the Assessment of Positive Symptoms (SAPS) PD version and SAPS H + D scales, Caregiver Burden Scale (CBS), and Clinical Global Impression (CGI) Improvement and Severity scales. Results: Of 171 who entered the OLE, 148 (87%) completed Week 4. Among patients who received placebo in the Core Study, mean (SD) change from OLE baseline to OLE Week 4 for the SAPS-PD was – 3.4 (6.3); p < 0.0001. Mean change from Core Study baseline to OLE Week 4 for SAPS-PD was similar among prior pimavanserin- and placebo-treated patients (–6.9 vs. –6.3). Improvement was similar with CGI-I, CGI-S, CBS, and SAPS-H + D in patients previously treated with placebo. Adverse events occurred in 92 (53.8%) patients during the 4-week OLE. Conclusion: Improvements at OLE Week 4 from pretreatment baseline were similar with placebo and pimavanserin in the Core Study. The beneficial effects observed with pimavanserin in the 6-week Core Study were maintained for 4 weeks in the blinded OLE, supporting the durability of response with pimavanserin 34 mg for PDP over 10 weeks.

Long-term, open-label, safety study of once-daily ropinirole extended/prolonged release in early and advanced Parkinson's disease

2014 ◽  
Vol 126 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Clare W. Makumi ◽  
Afsaneh Asgharian ◽  
Jeffrey Ellis ◽  
Soraya Shaikh ◽  
Teri Jimenez ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Prolonged Release ◽  
Open Label ◽  
Safety Study ◽  
Once Daily ◽  
Advanced Parkinson’S Disease
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