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).

Eslicarbazepine acetate exposure in pregnant women with epilepsy.

Purpose: Epilepsy is a common neurologic disorder requiring continued treatment during pregnancy. Treatment with antiepileptic drugs (AEDs) is needed for seizure control, but the risk of adverse events has to be minimized for both mother and foetus. Available data on pregnancy and foetal/postnatal outcomes following eslicarbazepine acetate (ESL) exposure via parent is herein presented for the first time.

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.

Adjunctive eslicarbazepine acetate: A pooled analysis of three phase III trials.

Objective: To assess the safety and efficacy of once-daily (QD) adjunctive eslicarbazepine acetate (ESL).

Methods: This post-hoc pooled analysis of three randomized, placebo-controlled trials (2093-301, -302, -304) involved adults with refractory partial-onset seizures (POS) receiving 1-3 antiepileptic drugs (AEDs). All studies included 8-week baseline, 2-week titration, and 12-week maintenance periods.

Opicapone pharmacokinetics and pharmacodynamics comparison between healthy Japanese and matched white subjects.

Opicapone (OPC) is a novel third-generation catechol-O-methyltransferase (COMT) inhibitor. This randomized, double-blind, parallel, placebo-controlled and multiple ascending dose study in 3 sequential groups of up to 38 (19 Japanese plus 19 white subjects) aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD; COMT activity) of opicapone between healthy Japanese and matched white subjects. Enrolled subjects received a once-daily morning administration of OPC (5, 25, or 50 mg) or placebo for 10 days, with plasma and urine concentrations of opicapone and its metabolites measured up to 144 hours postdose, including S-COMT activity.

Oxidative stress by Haemonchus contortus in lambs: Influence of treatment with zinc edetate.

The aim of the present study was to assess the effects of zinc edetate on the oxidative stress of lambs infected by Haemonchus contortus. Twenty-four lambs were allocated into four groups: Group I--uninfected animals; Group II--uninfected animals treated subcutaneously with zinc edetate; Group III--animals infected by H. contortus and Group IV--animals infected and treated.

Effect of zinc supplementation on ecto-adenosine deaminase activity in lambs infected by Haemonchus contortus: highlights on acute phase of disease.

Haemonchus contortus (order Strongylida) is a common parasitic nematode infecting small ruminants and causing significant economic losses worldwide. It induces innate and adaptive immune responses, which are essential for the clearance of this nematode from the host. Ecto-adenosine deaminase (E-ADA) is an enzyme that plays an important role in the immune system, while Zinc (Zn) has been found playing a critical role in E-ADA catalysis.

Experimental infection by Haemonchus contortus in lambs: influence of disease on purine levels in serum.

The aim of this study was to evaluate the purine levels of lambs experimentally infected with Haemonchus contortus. A total of 12 healthy lambs were divided into two groups, composed of 6 animals each: Group A represented the healthy animals (uninfected), while in Group B the animals were infected with 15 000 larvae of H. contortus.

Etamicastat, a novel dopamine β-hydroxylase inhibitor: tolerability, pharmacokinetics, and pharmacodynamics in patients with hypertension.

Background: Etamicastat is a dopamine β-hydroxylase (DβH) inhibitor currently in clinical development for the treatment of hypertension and heart failure.

Objective: This study assessed the tolerability, pharmacokinetics, and pharmacodynamics of etamicastat in patients with arterial hypertension.

Methods: This randomized, double-blind, placebo-controlled study was conducted in male patients aged between 18 and 65 years with mild to moderate hypertension.

Effect of moderate liver impairment on the pharmacokinetics of opicapone.

Purpose: Opicapone (OPC) is a novel catechol-O-methyltransferase (COMT) inhibitor to be used as adjunctive therapy in levodopa-treated patients with Parkinson's disease. The purpose of this study was to evaluate the effect of moderate liver impairment on the pharmacokinetics (PK) and pharmacodynamics (PD; effect on COMT activity) of OPC.

Methods: An open-label, parallel-group study in patients (n = 8) with moderate liver impairment (Child-Pugh category B, score of 7 to 9) and matched healthy subjects (n = 8, control) with normal liver function.

Human disposition, metabolism and excretion of etamicastat, a reversible, peripherally selective dopamine β-hydroxylase inhibitor.

Aims: Etamicastat is a reversible dopamine-β-hydroxylase inhibitor that decreases noradrenaline levels in sympathetically innervated tissues and slows down sympathetic nervous system drive. In this study, the disposition, metabolism and excretion of etamicastat were evaluated following [(14)C]-etamicastat dosing.

Methods: Healthy Caucasian males (n = 4) were enrolled in this single-dose, open-label study.

Metabolism, intake, and digestibility of lambs supplemented with organic chromium.

The aim of the present study was to evaluate the metabolism of organic chromium and its effect on digestibility and intake of lambs. Four 4-month-old male lambs, each weighing 28 kg, were used. The animals were kept in metabolic cages for a period of 20 days (15 days of adaptation and 5 days of experimentation), in two experimental phases, with inverted treatments.

Opicapone: a short lived and very long acting novel catechol-O-methyltransferase inhibitor following multiple dose administration in healthy subjects.

Aims: The aim of this study was to assess the tolerability, pharmacokinetics and inhibitory effect on erythrocyte soluble catechol-O-methyltransferase (S-COMT) activity following repeated doses of opicapone.

Methods: This randomized, placebo-controlled, double-blind study enrolled healthy male subjects who received either once daily placebo or opicapone 5, 10, 20 or 30 mg for 8 days.

Results: Opicapone was well tolerated.

Pharmacokinetics, pharmacodynamics and tolerability of opicapone, a novel catechol-O-methyltransferase inhibitor, in healthy subjects: prediction of slow enzyme-inhibitor complex dissociation of a short-living and very long-acting inhibitor.

Background And Objectives: Opicapone is a novel catechol-O-methyltransferase (COMT) inhibitor. The purpose of this study was to evaluate the tolerability, pharmacokinetics (including the effect of food) and pharmacodynamics (effect on COMT activity) following single oral doses of opicapone in young healthy male volunteers.

Methods: Single rising oral doses of opicapone (10, 25, 50, 100, 200, 400, 800 and 1,200 mg) were administered to eight groups of eight subjects per group (two subjects randomized to placebo and six subjects to opicapone), under a double-blind, randomized, placebo-controlled design.

Steady-state plasma and cerebrospinal fluid pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine in healthy volunteers.

Purpose: To evaluate the pharmacokinetics and tolerability of once-daily eslicarbazepine acetate (ESL) and twice-daily oxcarbazepine (OXC) and their metabolites in cerebrospinal fluid (CSF) and plasma following repeated oral administration.

Methods: Single-center, open-label, randomized, parallel-group study in healthy volunteers. Volunteers in ESL group (n = 7) received 600 mg on days 1-3 and 1,200 mg on days 4-9, once daily.

Pharmacokinetics and tolerability of etamicastat following single and repeated administration in elderly versus young healthy male subjects: an open-label, single-center, parallel-group study.

Background: Etamicastat is a new dopamine-β-hydroxylase (DβH) inhibitor currently in clinical development for the treatment of hypertension and heart failure.

Objectives: To evaluate the pharmacokinetics and tolerability of etamicastat after single and repeated administration in elderly subjects (aged ≥65 years) relative to young adult healthy controls (aged 18-45 years).

Methods: This was a single-center, open-label, parallel-group study in young male adults (n = 13; mean [SD] age 32.

Effect of food on the pharmacokinetic profile of etamicastat (BIA 5-453).

Background: Etamicastat is a novel, potent, and reversible peripheral dopamine-β-hydroxylase inhibitor that has been administered orally at doses up to 600 mg once daily for 10 days to male healthy volunteers and appears to be well tolerated.

Objective: The aim of this study was to investigate the effect of food on the pharmacokinetics of etamicastat.

Material And Methods: A single-center, open-label, randomized, two-way crossover study in 12 healthy male subjects was performed.

Single-dose tolerability, pharmacokinetics, and pharmacodynamics of etamicastat (BIA 5-453), a new dopamine β-hydroxylase inhibitor, in healthy subjects.

The safety, tolerability, pharmacokinetics, and pharmacodynamics of etamicastat (BIA 5-453), a novel dopamine β-hydroxylase (DβH) inhibitor, were investigated in 10 sequential groups of 8 healthy male subjects under a double-blind, randomized, placebo-controlled design. In each group, 6 subjects received a single dose of etamicastat (2, 10, 20, 50, 100, 200, 400, 600, 900, or 1200 mg) and 2 subjects received placebo. Etamicastat was well tolerated at all dose levels tested.

Safety, tolerability, and pharmacokinetics of etamicastat, a novel dopamine-β-hydroxylase inhibitor, in a rising multiple-dose study in young healthy subjects.

Background: Activation of the sympathetic nervous system is an important feature in hypertension and congestive heart failure. A strategy for directly modulating sympathetic nerve function is to reduce the biosynthesis of norepinephrine (noradrenaline) via inhibition of dopamine-β-hydroxylase (DβH).

Objective: To assess the safety, tolerability, and pharmacokinetics of etamicastat (BIA 5-453), a new DβH inhibitor, following repeated dosing.

Effect of eslicarbazepine acetate and oxcarbazepine on cognition and psychomotor function in healthy volunteers.

The results of two single-blind studies conducted to evaluate the cognitive and psychomotor effects of eslicarbazepine acetate and oxcarbazepine following single and repeated administration in healthy volunteers are reported. The cognitive and psychomotor evaluation consisted of several computerized and paper-and-pencil measures. Eslicarbazepine acetate and oxcarbazepine had similar overall cognitive profiles and did not cause clinically relevant cognitive impairment.

Pharmacokinetic-pharmacodynamic interaction between nebicapone and controlled-release levodopa/benserazide: a single-center, Phase I, double-blind, randomized, placebo-controlled, four-way crossover study in healthy subjects.

Background: Nebicapone is a reversible catechol-O-methyltransferase (COMT) inhibitor. Coadministration of a COMT inhibitor with levodopa and a dopa-decarboxylase inhibitor (carbidopa or benserazide) increases levodopa exposure and its therapeutic effect.

Objectives: The primary objective of this study was to investigate the effect of nebicapone (50, 100, and 200 mg), compared with placebo, on levodopa pharmacokinetics when coadministered with a single dose of controlled-release levodopa 100 mg/benserazide 25 mg.