Opicapone for Parkinson's disease-related sleep disturbances: The OASIS clinical trial.

BackgroundWhile sleep disturbances are among the most frequent non-motor symptoms of Parkinson's disease (PD), there is a lack of evidence to support its treatment.ObjectiveTo evaluate the efficacy of opicapone 50 mg in treating sleep disturbances in patients with PD and end-of-dose motor fluctuations.MethodsOASIS was an exploratory, open-label, single-arm clinical trial in PD patients with end-of-dose motor fluctuations and associated sleep disturbances.

Opicapone as adjunct to levodopa in treated Parkinson's disease without motor complications: A randomized clinical trial.

Background: Catechol-O-methyl transferase (COMT) inhibitors are routinely used to manage motor fluctuations in Parkinson's disease (PD). We assessed the effect of opicapone on motor symptom severity in levodopa-treated patients without motor complications.

Methods: This was a randomized, double-blind, 24-week, placebo-controlled study of opicapone 50 mg as adjunct to levodopa (NCT04978597).

Opicapone for the treatment of early wearing-off in levodopa-treated Parkinson's disease: pooled analysis of patient level data from two randomized open-label studies.

Background: The wearing-off phenomenon is a key driver of medication change for patients with Parkinson's disease (PD) treated with levodopa. Common first-line options include increasing the levodopa dose or adding a catechol-O-methyltransferase (COMT) inhibitor, but there are no trials comparing the efficacy of these approaches. We evaluated the effectiveness of adjunct opicapone versus an additional 100 mg levodopa dose in PD patients with early wearing-off using pooled data from 2 randomized studies.

OFF-times before, during, and after nighttime sleep periods in Parkinson's disease patients with motor fluctuations and the effects of opicapone: A post hoc analysis of diary data from BIPARK-1 and -2.

Introduction: In BIPARK-1 and BIPARK-2, addition of once-daily opicapone to levodopa/carbidopa significantly reduced daily "OFF"-time relative to placebo in adults with Parkinson's disease (PD) and motor fluctuations. Diary data from these studies were pooled and analyzed post hoc to characterize "OFF"-times around nighttime sleep and to explore the effects of opicapone 50 mg.

Methods: "OFF" before sleep (OBS), "OFF during the nighttime sleep period" (ODNSP), early morning "OFF" (EMO), and duration of nighttime sleep and awake periods were analyzed descriptively at baseline.

The safety/tolerability of opicapone when used early in Parkinson's disease patients with levodopa-induced motor fluctuations: A analysis of BIPARK-I and II.

Introduction: analyses of the BIPARK-I and II trials previously demonstrated that opicapone (OPC) 50 mg was efficacious over the whole trajectory of motor fluctuation evolution in patients with Parkinson's disease (PD) and end-of-dose motor fluctuations, with enhanced efficacy in patients who were earlier vs. later in their disease course and levodopa treatment pathway. Complementary analyses were performed to evaluate the safety/tolerability of OPC following the same pre-defined segmentation of the wide spectrum of duration of both PD and levodopa therapy, as well as of motor fluctuation history, in this patient population.

Effect of Opicapone on Levodopa Pharmacokinetics in Patients with Fluctuating Parkinson's Disease.

Background: Inhibiting catechol-O-methyltransferase extends the plasma half-life of levodopa, potentially allowing physicians to optimize the levodopa regimen in patients with Parkinson's disease (PD) experiencing motor fluctuations.

Objectives: To evaluate the effects of once-daily opicapone on levodopa plasma pharmacokinetics and motor response when added to two different levodopa dosing regimens.

Methods: A total of 24 patients with PD and motor fluctuations were enrolled in an exploratory, open-label, modified cross-over trial.

Opicapone as an Add-on to Levodopa in Patients with Parkinson's Disease Without Motor Fluctuations: Rationale and Design of the Phase III, Double-Blind, Randomised, Placebo-Controlled EPSILON Trial.

Introduction: Levodopa remains the cornerstone treatment for Parkinson's disease (PD) but its use is associated with the development of 'wearing-off' fluctuations and other motor and non-motor complications over time. Adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/dopa decarboxylase (DDC) inhibitor therapy reduces fluctuations in the profile of plasma levodopa levels following oral dosing, and can therefore be beneficial for the management of motor complications. The objective of the EPSILON study is to investigate the efficacy of opicapone (OPC; a third-generation, once-daily COMT inhibitor) in enhancing the clinical benefit of levodopa in patients in earlier stages of PD, without end-of-dose motor fluctuations.

Opicapone versus placebo in the treatment of Parkinson's disease patients with end-of-dose motor fluctuation-associated pain: rationale and design of the randomised, double-blind OCEAN (OpiCapone Effect on motor fluctuations and pAiN) trial.

Background: Optimisation of dopaminergic therapy may alleviate fluctuation-related pain in Parkinson's disease (PD). Opicapone (OPC) is a third-generation, once-daily catechol-O-methyltransferase inhibitor shown to be generally well tolerated and efficacious in reducing OFF-time in two pivotal trials in patients with PD and end-of-dose motor fluctuations. The OpiCapone Effect on motor fluctuations and pAiN (OCEAN) trial aims to investigate the efficacy of OPC 50 mg in PD patients with end-of-dose motor fluctuations and associated pain, when administered as adjunctive therapy to existing treatment with levodopa/dopa decarboxylase inhibitor (DDCi).

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

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). analyses of these trials evaluated the efficacy of OPC following pre-defined segmentation of the wide spectrum of motor fluctuations in PD. Data from matching treatment arms in BIPARK-I and -II were combined for the placebo (PLC) and OPC 50-mg groups, and exploratory analyses were performed to investigate the efficacy of OPC 50 mg vs.

Redefining the strategy for the use of COMT inhibitors in Parkinson's disease: the role of opicapone.

Introduction: Levodopa remains the gold-standard Parkinson's disease (PD) treatment, but the inevitable development of motor complications has led to intense activity in pursuit of its optimal delivery.

Areas Covered: Peripheral inhibition of dopa-decarboxylase has long been considered an essential component of levodopa treatment at every stage of illness. In contrast, only relatively recently have catechol-O-methyltransferase (COMT) inhibitors been utilized to block the other major pathway of degradation and optimize levodopa delivery to the brain.

Safety, Tolerability, and Pharmacokinetics of FAAH Inhibitor BIA 10-2474: A Double-Blind, Randomized, Placebo-Controlled Study in Healthy Volunteers.

This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of BIA 10-2474, a fatty acid amide hydrolase (FAAH) inhibitor, after first administration to healthy male and female participants. Participants (n = 116) were recruited into this phase I, double-blind, randomized, placebo-controlled, single ascending dose and multiple ascending dose (10-day) study. The primary outcome was the safety and tolerability of BIA 10-2474.

Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: the OPTIPARK open-label study.

Background: The efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials.

Methods: OPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions.

Correction to: Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: the OPTIPARK open-label study.

An amendment to this paper has been published and can be accessed via the original article.

Efficacy and safety of eslicarbazepine acetate as adjunctive therapy for refractory focal-onset seizures in children: A double-blind, randomized, placebo-controlled, parallel-group, multicenter, phase-III clinical trial.

Purpose: This was a phase-III, randomized, double-blind, placebo-controlled study aimed to evaluate efficacy and tolerability of eslicarbazepine acetate (ESL) as adjunctive therapy in pediatric patients with refractory focal-onset seizures (FOS).

Methods: Children (2-18 years old) with FOS, receiving 1-2 antiepileptic drugs, were randomized to ESL or placebo. Treatment was started at 10 mg/kg/day, up-titrated up to 20-30 mg/kg/day, and maintained for 12 weeks, followed by one-year open-label follow-up.

Safety Profile of Opicapone in the Management of Parkinson's Disease.

Background: Opicapone is a catechol O-methyltransferase (COMT) inhibitor indicated for use as adjunct to levodopa therapy in patients with Parkinson's disease (PD) and motor fluctuations.

Objective: To characterize the safety and tolerability of adjunct opicapone (25 and 50 mg) in a pooled population of levodopa-treated PD patients who participated in the opicapone Phase-3 clinical program.

Methods: Patient-level data (placebo, opicapone 25 mg and 50 mg) from the BIPARK-1 and BIPARK-2 double-blind and open-label studies were combined.

Safety, Tolerability and Efficacy of Eslicarbazepine Acetate as Adjunctive Therapy in Patients Aged ≥ 65 Years with Focal Seizures.

Background: The incidence of epilepsy is high within the first few years of life, stabilizes over the second through fifth decades, and then rises again. Treatment of elderly patients with antiepileptic drugs (AEDs) is complicated by increased sensitivity to drug effects, altered pharmacokinetics and an increased risk for drug interactions due to polytherapy. On the other hand, the safety and efficacy data of AEDs attained during clinical development programmes are relatively limited for this age group.

Effectiveness of opicapone and switching from entacapone in fluctuating Parkinson disease.

Objective: To evaluate the effectiveness of opicapone as add-on to levodopa and the effects of switching from entacapone over 1 year of treatment in patients with fluctuating Parkinson disease.

Methods: After completion of a placebo- and entacapone-controlled double-blind study of opicapone (5, 25, or 50 mg), 495 patients continued to a 1-year extension phase in which patients were treated with opicapone. Patients began with once-daily opicapone 25 mg for 1 week, followed by individually tailored levodopa and/or opicapone dose adjustments.

Efficacy and safety of eslicarbazepine acetate versus controlled-release carbamazepine monotherapy in newly diagnosed epilepsy: A phase III double-blind, randomized, parallel-group, multicenter study.

Objective: We assessed the efficacy and safety of once-daily eslicarbazepine acetate in comparison with twice-daily (BID) controlled-release carbamazepine (carbamazepine-CR) monotherapy in newly diagnosed focal epilepsy patients.

Methods: This randomized, double-blind, noninferiority trial (NCT01162460) utilized a stepwise design with 3 dose levels. Patients who remained seizure-free for the 26-week evaluation period (level A: eslicarbazepine acetate 800 mg/carbamazepine-CR 200 mg BID) entered a 6-month maintenance period.

Pooled efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: Data from four double-blind placebo-controlled pivotal phase III clinical studies.

Purpose: Pooled evaluation of the key efficacy and safety profile of eslicarbazepine acetate (ESL) added-on to stable antiepileptic therapy in adults with focal-onset seizures.

Methods: Data from 1703 patients enrolled in four phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2 week titration period, ESL was administered at 400 mg, 800 mg, and 1200 mg once-daily doses for 12 weeks (maintenance period).

Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial.

Importance: Catechol O-methyltransferase (COMT) inhibitors are an established treatment for end-of-dose motor fluctuations associated with levodopa therapy in patients with Parkinson disease (PD). Current COMT inhibitors carry a high risk for toxic effects to hepatic cells or show moderate improvement. Opicapone was designed to be effective without the adverse effects.