| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Monotherapy for Patients With Newly Diagnosed Partial-onset Seizures:a Double-blind, Randomized, Active-controlled, Parallel-group, Multicenter Clinical Study [NCT01162460] | Phase 3 | 815 participants (Actual) | Interventional | 2010-12-31 | Completed |
| A Phase 1, Open-label Drug Interaction Study Between Eslicarbazepine Acetate 1200mg and Lamotrigine 150mg Following Multiple Doses Administrations in Healthy Male Volunteers [NCT02283801] | Phase 1 | 32 participants (Actual) | Interventional | 2006-11-30 | Completed |
| Steady-state Pharmacokinetics of BIA 2-093 and Oxcarbazepine in Healthy Volunteers [NCT01679002] | Phase 1 | 12 participants (Actual) | Interventional | 2003-10-31 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate as First Add-on to Levetiracetam or Lamotrigine Monotherapy or as Later Adjunctive Treatment for Subjects With Uncontrolled Partial-onset Seizures: A Multicenter, Open-label, Non-randomized Trial [NCT03116828] | Phase 4 | 102 participants (Actual) | Interventional | 2017-07-07 | Completed |
| Double-Blind, Randomized, Historical Control Study of the Safety and Efficacy of Eslicarbazepine Acetate Monotherapy in Subjects With Partial Epilepsy Not Well Controlled by Current Antiepileptic Drugs [NCT01091662] | Phase 3 | 172 participants (Actual) | Interventional | 2010-06-30 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Trial [NCT00988429] | Phase 3 | 653 participants (Actual) | Interventional | 2008-12-02 | Completed |
| An Open-label Eslicarbazepine Acetate Long-term Safety and Tolerability Study in Children and Adolescents (4 - 17 Years) [NCT03108729] | Phase 3 | 0 participants (Actual) | Interventional | 2017-07-06 | Withdrawn(stopped due to The study was not withdrawn for safety reasons. The sponsor received approval for the treatment of partial-onset seizures in patients 4 years of age and older) |
| ZEBinix Retention Rate in Epilepsy in Elderly Patients [NCT04221282] | | 50 participants (Anticipated) | Observational | 2019-04-01 | Recruiting |
| Long Term Eslicarbazepine Acetate Extension Study [NCT00910247] | Phase 3 | 274 participants (Actual) | Interventional | 2009-08-31 | Completed |
| Double-Blind, Randomized, Historical Control Study of the Safety and Efficacy of Eslicarbazepine Acetate Monotherapy in Subjects With Partial Epilepsy Not Well Controlled by Current Antiepileptic Drugs [NCT00866775] | Phase 3 | 193 participants (Actual) | Interventional | 2009-04-30 | Completed |
| A Dose Randomized, Double-blind, Placebo Controlled, Single and Multiple Dosing, Dose-escalation Phase I Clinical Trial to Investigate the Safety, Tolerability and Pharmacokinetic Characteristics of Zebinix (Eslicarbazepine Acetate) After Oral Administrat [NCT04095182] | Phase 1 | 50 participants (Actual) | Interventional | 2019-08-22 | Completed |
| [NCT01878578] | Phase 1 | 4 participants (Actual) | Interventional | 2002-11-30 | Terminated(stopped due to prematurely terminated due to impossibility of recruiting the planned number of patients by the study centre.) |
| A Phase 3, Double Blind, Randomized, Placebo Controlled, Parallel Group, Multicenter Clinical Study of Eslicarbazepine Acetate in Diabetic Neuropathic Pain [NCT01129960] | Phase 3 | 332 participants (Actual) | Interventional | 2010-11-30 | Terminated |
| Efficacy and Safety of BIA 2-093 as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomized, Placebo-controlled, Parallel-group, Multicenter Clinical Trial [NCT00957372] | Phase 3 | 253 participants (Actual) | Interventional | 2004-12-31 | Completed |
| Effect of Eslicarbazepine Acetate on the Pharmacokinetics of Gliclazide in Healthy Volunteers [NCT02777671] | Phase 1 | 20 participants (Actual) | Interventional | 2007-10-31 | Completed |
| A Phase I, Single Centre, Open, Randomised, Parallel Study to Evaluate the Pharmacokinetics and Tolerability of Multiple Doses of Eslicarbazepine Acetate and Oxcarbazepine in Healthy Subject [NCT00900237] | Phase 1 | 14 participants (Actual) | Interventional | 2008-11-30 | Completed |
| Effect of Eslicarbazepine Acetate on the Pharmacokinetics of Metformin in Healthy Volunteers [NCT00971295] | Phase 1 | 20 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Double-Blind, Randomized, Two Period Crossover Comparison of the Cognitive and Behavioral Effects of Eslicarbazepine Acetate and Carbamazepine in Healthy Adults [NCT02912364] | Phase 4 | 46 participants (Actual) | Interventional | 2016-07-31 | Completed |
| Effect of Repeated Administration of Eslicarbazepine Acetate (BIA 2-093) 800mg Once-daily on the Pharmacokinetics of a Combined Oral Contraceptive in Healthy Female Subjects [NCT00898560] | Phase 1 | 20 participants (Actual) | Interventional | 2008-09-30 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial. [NCT00957684] | Phase 3 | 402 participants (Actual) | Interventional | 2004-07-31 | Completed |
| Effect of Repeated Administration of Eslicarbazepine Acetate on the Pharmacokinetics of Simvastatin in Healthy Subjects [NCT00987558] | Phase 1 | 30 participants (Actual) | Interventional | 2009-06-30 | Completed |
| A Phase 3, Double Blind, Randomized, Placebo Controlled, Parallel Group, Multicenter Clinical Study of Eslicarbazepine Acetate in Post-Herpetic Neuralgia [NCT01124097] | Phase 3 | 240 participants (Actual) | Interventional | 2010-09-30 | Terminated |
| A Non-Interventional, Prospective Study to Assess Seizure Control and Tolerability of Eslicarbazepine Acetate as Adjunctive Therapy to One Baseline Antiepileptic Drug, in Adults With Partial-Onset Seizures With or Without Secondary Generalization [NCT01532726] | | 56 participants (Actual) | Observational | 2012-03-31 | Completed |
| Single-dose Pharmacokinetics and Relative Bioavailability of an Oral Suspension and Two Tablet Formulations of BIA 2-093 in Healthy Volunteers [NCT02279667] | Phase 1 | 18 participants (Actual) | Interventional | 2004-02-29 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled, Sequential Multiple Ascending Dose Study of the Safety and Pharmacokinetics of Eslicarbazepine Acetate in Adult Healthy Volunteers [NCT01879332] | Phase 1 | 16 participants (Actual) | Interventional | 2006-12-31 | Completed |
| An Open-label, Single-dose, Single-centre Study, Investigating the Pharmacokinetics of BIA 2-093 in Subjects With Various Degrees of Renal Impairment [NCT02281422] | Phase 1 | 40 participants (Actual) | Interventional | 2005-03-31 | Completed |
| Single Dose Crossover Comparative Bioavailability Study of Eslicarbazepine Acetate 400mg, 600mg and 800mg Tablets Clinical Trial Formulation (CTF) Versus the To-be-marketed Formulation (TBM) in Healthy Male and Female [NCT02283840] | Phase 1 | 60 participants (Actual) | Interventional | 2007-05-31 | Completed |
| Pharmacokinetic Interaction Study Between Eslicarbazepine Acetate and Carbamazepine in Healthy Subject [NCT02284854] | Phase 1 | 43 participants (Actual) | Interventional | 2009-07-31 | Completed |
| Phase I, Open-label Drug Interaction Study Between Eslicarbazepine Acetate 1200mg and Phenytoin 300 mg Following Multiple Dose Administrations in Healthy Male Volunteers [NCT02283827] | Phase 1 | 32 participants (Actual) | Interventional | 2007-01-31 | Completed |
| The Effect of BIA 2-093 on the Steady-state Pharmacodynamic and Pharmacokinetic Profiles of Warfarin in Healthy Volunteers [NCT02287415] | Phase 1 | 13 participants (Actual) | Interventional | 2002-05-31 | Completed |
| Tolerability and Pharmacokinetics of a Single 900 mg Oral Dose of BIA 2-093 and Oxcarbazepine in Healthy Volunteers [NCT01678976] | Phase 1 | 13 participants (Actual) | Interventional | 2002-03-31 | Completed |
| Effect of BIA 2-093 on the Pharmacokinetics of a Combined Oral Contraceptive in Healthy Female Volunteers [NCT02281448] | Phase 1 | 20 participants (Actual) | Interventional | 2005-03-31 | Completed |
| An Open-label, Multiple-dose, Single-centre Study, Investigating the Pharmacokinetics of BIA 2-093 in Subjects With Moderate Hepatic Impairment. [NCT02281526] | Phase 1 | 17 participants (Actual) | Interventional | 2005-05-31 | Completed |
| Comparative Bioavailability Study of Two Different Sources of Eslicarbazepine Acetate in Healthy Subjects [NCT02284880] | Phase 1 | 40 participants (Actual) | Interventional | 2010-10-31 | Completed |
| Efficacy and Safety of BIA 2-093 as Adjunctive Therapy for Refractory Partial Seizures in a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial [NCT00957047] | Phase 3 | 395 participants (Actual) | Interventional | 2004-07-31 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate (BIA 2093) as Therapy for Patients With Post-herpetic Neuralgia: a Double-blind, Double-dummy, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial [NCT00981227] | Phase 2 | 567 participants (Actual) | Interventional | 2007-11-30 | Completed |
| The Tolerability and Effect of Food on the Pharmacokinetics of a Single 800 mg Oral Dose of BIA 2-093 in Healthy Male Volunteers [NCT02170649] | Phase 1 | 12 participants (Actual) | Interventional | 2001-09-30 | Completed |
| A Single Centre, Phase I, Double-blind, Randomised, Placebo-controlled Study to Investigate the Safety, Tolerability, Pharmacokinetic Profile and Effects on EEG of Single Rising Oral Doses of BIA 2-093 When Given to Healthy Male Adult Volunteers. [NCT02171195] | Phase 1 | 64 participants (Actual) | Interventional | 2000-07-31 | Completed |
| Single-dose and Steady-state Pharmacokinetics of BIA 2-093 and Its Metabolites in Healthy Elderly Subjects Compared With Those in Healthy Young Subjects [NCT02172755] | Phase 1 | 30 participants (Actual) | Interventional | 2002-06-30 | Completed |
| Effects of Eslicarbazepine Acetate (Esl, Bia 2-093) on Cognitive Function in Children With Partial Onset Seizures: an add-on, Double-blind, Randomised, Placebo-controlled, Parallel Group, Multicentre Clinical Trial [NCT01527513] | Phase 2 | 123 participants (Actual) | Interventional | 2010-08-31 | Completed |
| Systematic Review: Retigabine for Adjunctive Therapy in Partial Epilepsy [NCT01587339] | | 6,498 participants (Actual) | Observational | 2010-09-30 | Completed |
| A Placebo-controlled Study to Investigate Safety and Efficacy of BIA 2-093 in Controlling Refractory Partial Seizures When Added to Ongoing Therapy [NCT02170077] | Phase 2 | 144 participants (Actual) | Interventional | 2002-04-30 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate (BIA 2 093) in Acute Manic Episodes Associated With Bipolar I Disorder in a Double Blind, Randomised, Dose Titration, Placebo Controlled, Multicentre Clinical Trial [NCT01822678] | Phase 2 | 161 participants (Actual) | Interventional | 2005-12-31 | Completed |
| A DOUBLE-BLIND, RANDOMISED, PLACEBO-CONTROLLED STUDY TO EVALUATE THE TOLERABILITY AND PHARMACOKINETICS OF TWO SINGLE AND MULTIPLE HIGH DOSE REGIMENS OF BIA 2-093 IN HEALTHY VOLUNTEERS [NCT01879345] | Phase 1 | 18 participants (Actual) | Interventional | 2004-10-31 | Completed |
| Food Effect and Dosage Form Proportionality Study of Eslicarbazepine Acetate Market Formulation in Healthy Volunteers [NCT02288312] | Phase 1 | 18 participants (Actual) | Interventional | 2007-05-31 | Completed |
| Disposition of Eslicarbazepine Acetate and Its Metabolites S-licarbazepine and R-licarbazepine Following Oral Administration in Healthy Volunteers [NCT02281591] | Phase 1 | 32 participants (Actual) | Interventional | 2006-06-30 | Completed |
| Double-blind Study in Paediatric Epileptic Subjects Aged From 5 to Less Than 8 Years to Compare the Subject Preference for ESL Suspension Formulation With Alternative Flavours [NCT02021461] | Phase 2 | 38 participants (Actual) | Interventional | 2012-12-31 | Completed |
| A Single Center, Single Dose, Open Label, Laboratory Blind, Randomized, Three Period, Six Sequence, Crossover Study to Determine the Bioequivalence of Two Different Sources of Eslicarbazepine Acetate (800 mg) and to Assess the Dose Equivalence of Two Diff [NCT03116321] | Phase 1 | 24 participants (Actual) | Interventional | 2016-12-03 | Completed |
| A Double-blind, Randomised, Placebo-controlled, Rising Multiple Dose Study to Investigate the Safety, Tolerability, Steady State Pharmacokinetic Profile and CNS Effects of BIA 2-093, in Young Healthy Male Volunteers. [NCT02171234] | Phase 1 | 32 participants (Actual) | Interventional | 2001-02-28 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) in Acute Manic Episodes Associated With Bipolar I Disorder in a Double-blind, Fixed Multiple Dose, Randomised, Placebo-controlled,Multicentre Clinical Trial. [NCT01824602] | Phase 2 | 38 participants (Actual) | Interventional | 2006-02-28 | Terminated(stopped due to Due to a slow recruitment rate) |
| Extension Study to Investigate the Efficacy, Safety, and Tolerability of Eslicarbazepine Acetate (BIA 2-093) in the Recurrence Prevention of Bipolar I Disorder [NCT01825837] | Phase 2 | 104 participants (Actual) | Interventional | 2006-03-31 | Completed |
| An Open-label, Multi-centre, Multi-national Post-marketing Non-interventional Prospective Study Evaluating Retention Rate, Seizure Control and Tolerability of Eslicarbazepine Acetate (ESL) as Adjunctive Treatment to One Baseline Antiepileptic Drug in Adul [NCT01830400] | | 254 participants (Actual) | Observational | 2012-04-30 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate (BIA 2 093) as Therapy for Patients With Painful Diabetic Neuropathy: a Double-blind, Double-dummy, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial [NCT00980746] | Phase 2 | 557 participants (Actual) | Interventional | 2007-11-30 | Completed |
| Efficacy and Safety Study of Eslicarbazepine Acetate (BIA 2 093) as Adjunctive Therapy for Refractory Partial Seizures in Children [NCT00988156] | Phase 3 | 304 participants (Actual) | Interventional | 2007-12-07 | Completed |
| The Effect of BIA 2-093 on the Steady-state Pharmacokinetics of Digoxin in Healthy Volunteers [NCT02172742] | Phase 1 | 13 participants (Actual) | Interventional | 2002-05-31 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate as Therapy in Subjects With Fibromyalgia: a Double-blind, Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial [NCT01820585] | Phase 2 | 528 participants (Actual) | Interventional | 2009-04-30 | Completed |
| A Phase-1, Open-label, Drug Interaction Study Between Eslicarbazepine Acetate 1200 mg and Topiramate 200 mg Following Multiple Dose Administrations in Healthy Male [NCT02283814] | Phase 1 | 32 participants (Actual) | Interventional | 2007-01-31 | Completed |
| Effects of Eslicarbazepine Acetate (BIA 2-093) on Cognition and Psychomotor Function: Single-blind, Single-centre, Single and Multiple Dose, Fixed-order, Placebocontrolled Trial in Healthy Volunteers [NCT02284828] | Phase 1 | 26 participants (Actual) | Interventional | 2007-09-30 | Completed |
| Safety and Efficacy of Eslicarbazepine Acetate (ESL) as Adjunctive Therapy for Partial Seizures in Elderly Patients [NCT01422720] | Phase 3 | 72 participants (Actual) | Interventional | 2010-04-30 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate as Preventive Therapy for Subjects With Migraine: a Doubleblind,Randomised, Placebo-controlled, Parallel-group, Multicentre Clinical Trial [NCT01820559] | Phase 2 | 452 participants (Actual) | Interventional | 2009-04-30 | Completed |
| Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) as Monotherapy for Patients With Newly Diagnosed Partial-onset Seizures: a Double-blind, Randomized, Active-controlled, Parallel-group, Multicenter Clinical Study - Open-label ESL Extension [NCT02484001] | Phase 3 | 206 participants (Actual) | Interventional | 2016-03-01 | Completed |
| A Randomized, Double-blind, Placebo-controlled and Open Label Active-controlled, 4-period Crossover Trial to Evaluate the Effect of Eslicarbazepine Acetate on Cardiac Repolarization in Healthy Adult Men and Women [NCT02283788] | Phase 1 | 67 participants (Actual) | Interventional | 2007-03-31 | Completed |
| Pharmacokinetics, Efficacy and Tolerability of BIA 2-093 in Children and Adolescents With Refractory Partial Epilepsy [NCT02170064] | Phase 2 | 35 participants (Actual) | Interventional | 2005-06-30 | Completed |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
| Trial | Outcome |
|---|
| NCT00866775 (16) [back to overview] | Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy. |
| NCT00866775 (16) [back to overview] | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). |
| NCT00866775 (16) [back to overview] | Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period. |
| NCT00866775 (16) [back to overview] | Percentage of Subjects With Increase of Body Weight >= 7% |
| NCT00866775 (16) [back to overview] | Percentage of Subjects Reaching Each of the Exit Events. |
| NCT00866775 (16) [back to overview] | Time on Eslicarbazepine Acetate Monotherapy. |
| NCT00866775 (16) [back to overview] | Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization. |
| NCT00866775 (16) [back to overview] | Change in Seizure Frequency From Baseline. |
| NCT00866775 (16) [back to overview] | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). |
| NCT00866775 (16) [back to overview] | Completion Rate |
| NCT00866775 (16) [back to overview] | Completion Rate During the 10 Weeks of Monotherapy |
| NCT00866775 (16) [back to overview] | Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method |
| NCT00866775 (16) [back to overview] | Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS). |
| NCT00866775 (16) [back to overview] | Standardized Seizure Frequency (SSF) by Period |
| NCT00866775 (16) [back to overview] | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). |
| NCT00866775 (16) [back to overview] | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L |
| NCT00898560 (3) [back to overview] | Cmax - Maximum Observed Plasma Concentration |
| NCT00898560 (3) [back to overview] | AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification |
| NCT00898560 (3) [back to overview] | AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity |
| NCT00900237 (2) [back to overview] | Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid |
| NCT00900237 (2) [back to overview] | AUC0-t AUC From Time Zero to the Last Sampling Time |
| NCT00910247 (17) [back to overview] | Number and Percent of Subjects With Treatment Emergent Adverse Events |
| NCT00910247 (17) [back to overview] | Number and Percentage of Subjects With Orthostatic Effects. |
| NCT00910247 (17) [back to overview] | Number and Percentage of Subjects With Potentially Clinically Significant Clinical Laboratory Evaluations |
| NCT00910247 (17) [back to overview] | Percentage of Subjects That Are Seizure-free During Study |
| NCT00910247 (17) [back to overview] | Percentage of Subjects With Increase of Body Weight ≥7% |
| NCT00910247 (17) [back to overview] | Responder Rate (Percentage of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). |
| NCT00910247 (17) [back to overview] | Time on Eslicarbazepine Acetate Monotherapy. |
| NCT00910247 (17) [back to overview] | Treatment Retention Time (Time to Withdrawal Due to Lack of Efficacy or Adverse Events) |
| NCT00910247 (17) [back to overview] | Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline. |
| NCT00910247 (17) [back to overview] | Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). |
| NCT00910247 (17) [back to overview] | Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L |
| NCT00910247 (17) [back to overview] | Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in Those Subjects With a MADRS Score of ≥14 at Screening |
| NCT00910247 (17) [back to overview] | Change in Seizure Frequency From Baseline. |
| NCT00910247 (17) [back to overview] | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). |
| NCT00910247 (17) [back to overview] | Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS). |
| NCT00910247 (17) [back to overview] | Completion Rate (% of Subjects Completing Each Visit Post-one Year). |
| NCT00910247 (17) [back to overview] | Completion Rate (% of Subjects Completing the One Year Treatment) |
| NCT00957047 (2) [back to overview] | PART I - Seizure Frequency |
| NCT00957047 (2) [back to overview] | PART II - Nº of Treatment-Emergent Adverse Events (TEAE) |
| NCT00957372 (2) [back to overview] | PART II: Nº of Treatment-Emergent Adverse Events (TEAE) |
| NCT00957372 (2) [back to overview] | Seizure Frequency |
| NCT00957684 (1) [back to overview] | Part I: Seizure Frequency |
| NCT00971295 (3) [back to overview] | AUC0-∞ - Area Under the Plasma Concentration From Time Zero to Infinity |
| NCT00971295 (3) [back to overview] | Cmax - Maximum Observed Plasma Concentration |
| NCT00971295 (3) [back to overview] | Tmax - Time of Occurrence of Cmax |
| NCT00980746 (1) [back to overview] | Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain |
| NCT00981227 (2) [back to overview] | Change in Mean Pain (NRPS) From Baseline to Endpoint by Total Daily Dose |
| NCT00981227 (2) [back to overview] | Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain |
| NCT00987558 (4) [back to overview] | Simvastatin Tmax (Time of Occurrence of Cmax) |
| NCT00987558 (4) [back to overview] | Simvastatin AUC0-∞ (AUC From Time Zero to Infinity) |
| NCT00987558 (4) [back to overview] | Simvastatin Cmax (Maximum Plasma Concentration) |
| NCT00987558 (4) [back to overview] | Simvastatin AUC0-t |
| NCT00988156 (2) [back to overview] | Change From Baseline in Seizure Frequency |
| NCT00988156 (2) [back to overview] | Responder Rate |
| NCT00988429 (2) [back to overview] | Proportion of Responders |
| NCT00988429 (2) [back to overview] | Seizure Frequency Over the 12-week Maintenance Period. |
| NCT01091662 (16) [back to overview] | Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method |
| NCT01091662 (16) [back to overview] | Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy. |
| NCT01091662 (16) [back to overview] | Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline |
| NCT01091662 (16) [back to overview] | Time on Eslicarbazepine Acetate Monotherapy. |
| NCT01091662 (16) [back to overview] | Change in Seizure Frequency From Baseline. |
| NCT01091662 (16) [back to overview] | Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31). |
| NCT01091662 (16) [back to overview] | Standardized Seizure Frequency (SSF) by Period |
| NCT01091662 (16) [back to overview] | Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline). |
| NCT01091662 (16) [back to overview] | Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L. |
| NCT01091662 (16) [back to overview] | Proportion (%) of Subjects Reaching Each Exit Criteria |
| NCT01091662 (16) [back to overview] | Proportion (%) of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period. |
| NCT01091662 (16) [back to overview] | Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS). |
| NCT01091662 (16) [back to overview] | Change in Total Score of MADRS From Baseline in Those Subjects With a MADRS Score of ≥14 at Randomization. |
| NCT01091662 (16) [back to overview] | Change in Total Score in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline . |
| NCT01091662 (16) [back to overview] | Completion Rate (% of Subjects Completing the 18 Weeks of Double-blind Treatment). |
| NCT01091662 (16) [back to overview] | Completion Rate During the 10 Weeks of Monotherapy (% of Subjects Entering the Monotherapy Period Who Complete). |
| NCT01124097 (1) [back to overview] | Change From Baseline to Endpoint in Mean Pain |
| NCT01129960 (1) [back to overview] | Change From Baseline to Endpoint in Mean Pain |
| NCT01422720 (2) [back to overview] | Change From Baseline in Standardized Seizure Frequency |
| NCT01422720 (2) [back to overview] | Number of Subjects With Reported Adverse Events (AE) |
| NCT01527513 (3) [back to overview] | Change From Baseline in Power of Attention Score to the End of the Double Blind (DB) Period |
| NCT01527513 (3) [back to overview] | Change From Baseline in Seizure Frequency During the One-year Open-Label (OL) |
| NCT01527513 (3) [back to overview] | Change From Baseline in Standardized Seizure Frequency - Part I |
| NCT01678976 (3) [back to overview] | Total of Subjects Reporting at Least One Adverse Event |
| NCT01678976 (3) [back to overview] | Maximum Drug Concentration (Cmax) |
| NCT01678976 (3) [back to overview] | Area Under the Plasma Concentration Versus Time Curve (AUC) |
| NCT01679002 (3) [back to overview] | AUC - Area Under the Plasma Concentration Versus Time Curve |
| NCT01679002 (3) [back to overview] | Number of of Subjects Reporting at Least One Adverse Event |
| NCT01679002 (3) [back to overview] | Cmax - Maximum Observed Plasma Drug Concentration |
| NCT01820559 (1) [back to overview] | Absolute Change From Baseline in the Frequency of Migraine Attacks |
| NCT01820585 (1) [back to overview] | Absolute Change From Baseline to Endpoint in Mean Pain |
| NCT01822678 (1) [back to overview] | Change in the Young Mania Rating Scale (YMRS) Total Score at the End of the 3-week Treatment Period, in Relation to the Baseline. |
| NCT01824602 (1) [back to overview] | Change in Young Mania Rating Scale (YMRS) Total Score From Baseline Until the End of the 3-week Treatment Period |
| NCT01825837 (1) [back to overview] | Proportion of Patients Who Showed no Worsening According to the Clinical Global Impression - Bipolar Version (CGI-BP) Scale (Intent-to-Treat Population) |
| NCT01879332 (1) [back to overview] | Number of Adverse Events Reported |
| NCT01879345 (4) [back to overview] | Number of Adverse Events Reported |
| NCT01879345 (4) [back to overview] | AUC0-τ |
| NCT01879345 (4) [back to overview] | Cmax - Maximum Observed Plasma Drug Concentration |
| NCT01879345 (4) [back to overview] | Tmax - the Time of Occurrence of Cmax |
| NCT02021461 (1) [back to overview] | Assessment of Taste Preference |
| NCT02170064 (3) [back to overview] | Time of Occurrence of Cmax (Tmax). |
| NCT02170064 (3) [back to overview] | Maximum Observed Plasma Drug Concentration (Cmax) Post-dose |
| NCT02170064 (3) [back to overview] | Percentage Change in Seizure Frequency During Each 4-week Treatment Period Compared to the Baseline Phase |
| NCT02170077 (1) [back to overview] | "The Percentage of Participants With a 50% or Greater Reduction in Seizure Frequency (Further Referred to as Responders) in a Treatment Period Compared to the Baseline Period" |
| NCT02170649 (4) [back to overview] | Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-oo) |
| NCT02170649 (4) [back to overview] | Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification (AUC0-t) |
| NCT02170649 (4) [back to overview] | Maximum Observed Plasma Concentration (Cmax) |
| NCT02170649 (4) [back to overview] | Time of Occurrence of Cmax (Tmax) |
| NCT02171195 (1) [back to overview] | Total Number of Adverse Events |
| NCT02171234 (3) [back to overview] | Total Number of Adverse Events |
| NCT02171234 (3) [back to overview] | Cmax |
| NCT02171234 (3) [back to overview] | AUC0-τ |
| NCT02172742 (3) [back to overview] | Cmax - Maximum Steady-state Plasma Concentration |
| NCT02172742 (3) [back to overview] | AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h |
| NCT02172742 (3) [back to overview] | Tmax - Time of Occurrence of Cmax at Steady-state |
| NCT02172755 (3) [back to overview] | Maximum Drug Concentration (Cmax) |
| NCT02172755 (3) [back to overview] | Tmax - Time of Maximum Observed Concentration |
| NCT02172755 (3) [back to overview] | AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point |
| NCT02279667 (4) [back to overview] | Tmax - the Time of Occurrence of Cmax |
| NCT02279667 (4) [back to overview] | Cmax - the Maximum Plasma Concentration |
| NCT02279667 (4) [back to overview] | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time |
| NCT02279667 (4) [back to overview] | AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity |
| NCT02281422 (3) [back to overview] | Cmax - Peak Plasma Concentration |
| NCT02281422 (3) [back to overview] | AUC(0-12h) - AUC From Time Zero to 12h |
| NCT02281422 (3) [back to overview] | Tmax (hr) - Time at Which Cmax Occurred |
| NCT02281448 (4) [back to overview] | AUC0-t |
| NCT02281448 (4) [back to overview] | Cmax |
| NCT02281448 (4) [back to overview] | Cmax - Maximum Observed Plasma BIA 2-194 Concentration |
| NCT02281448 (4) [back to overview] | Tmax |
| NCT02281526 (2) [back to overview] | Cmax - Peak Plasma Concentration |
| NCT02281526 (2) [back to overview] | Area Under the Plasma Concentration Versus Time Curve, AUC(0-tlast). |
| NCT02281591 (4) [back to overview] | Cmax - the Maximum Plasma Concentration |
| NCT02281591 (4) [back to overview] | Tmax - the Time of Occurrence of Cmax |
| NCT02281591 (4) [back to overview] | AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity |
| NCT02281591 (4) [back to overview] | AUC0-t - the Area Under the Plasma Concentration-time Curve to Last Measurable Time Point |
| NCT02283788 (1) [back to overview] | QTcI - QT Interval Individually Corrected for Heart Rate - Day 5 |
| NCT02283814 (3) [back to overview] | AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State. |
| NCT02283814 (3) [back to overview] | Tmax - the Time of Occurrence of Cmax |
| NCT02283814 (3) [back to overview] | Cmax - the Maximum Plasma Concentration |
| NCT02283827 (3) [back to overview] | Cmax - the Maximum Plasma Concentration |
| NCT02283827 (3) [back to overview] | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time |
| NCT02283827 (3) [back to overview] | Tmax - the Time of Occurrence of Cmax |
| NCT02283840 (3) [back to overview] | Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005 |
| NCT02283840 (3) [back to overview] | AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time |
| NCT02283840 (3) [back to overview] | Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005 |
| NCT02284828 (6) [back to overview] | Motor Reaction Time (MRT) (ms): Change From Baseline at Each Time Point During Acute Dosing Phase |
| NCT02284828 (6) [back to overview] | Motor Reaction Time (MRT) (ms): Raw Values at Each Time Point During Acute Dosing Phase |
| NCT02284828 (6) [back to overview] | Recognition Reaction Time (RRT) (ms): Raw Values at Each Time Point During Acute Dosing Phase |
| NCT02284828 (6) [back to overview] | Total Reaction Time (TRT) (ms): Raw Values at Each Time Point During Acute Dosing Phase |
| NCT02284828 (6) [back to overview] | Recognition Reaction Time (RRT) (ms): Change From Baseline at Each Time Point During Acute Dosing Phase |
| NCT02284828 (6) [back to overview] | Total Reaction Time (TRT) (ms): Change From Baseline at Each Time Point During Acute Dosing Phase |
| NCT02284854 (6) [back to overview] | Cmax (CBZ) - the Maximum Plasma Concentration |
| NCT02284854 (6) [back to overview] | AUC0-t (CBZE) - Area Under the Curve to Last Measurable Concentration for CBZE |
| NCT02284854 (6) [back to overview] | Cmax (BIA 2-093) - the Maximum Plasma Concentration |
| NCT02284854 (6) [back to overview] | AUC0-t (CBZ) - Area Under the Curve to Last Measurable Concentration for CBZ |
| NCT02284854 (6) [back to overview] | Cmax (CBZE) - the Maximum Plasma Concentration |
| NCT02284854 (6) [back to overview] | AUC0-t (BIA 2-093) - Area Under the Curve to Last Measurable Concentration for BIA 2-093 |
| NCT02284880 (3) [back to overview] | AUC0-t - Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification |
| NCT02284880 (3) [back to overview] | Cmax - Maximum Plasma Concentration |
| NCT02284880 (3) [back to overview] | Tmax - Time of Occurrence of Cmax |
| NCT02287415 (3) [back to overview] | AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h, the Dosing Interval |
| NCT02287415 (3) [back to overview] | Cmax - Maximum Steady-state Plasma Concentration |
| NCT02287415 (3) [back to overview] | Tmax - Time of Occurrence of Cmax |
| NCT02288312 (4) [back to overview] | AUC0-∞ (BIA 2-005) |
| NCT02288312 (4) [back to overview] | Tmax (BIA 2-005) |
| NCT02288312 (4) [back to overview] | Cmax (BIA 2-005) |
| NCT02288312 (4) [back to overview] | AUC0-t (BIA 2-005) |
| NCT02912364 (5) [back to overview] | Profile of Mood States (POMS) Score. |
| NCT02912364 (5) [back to overview] | MCG Paragraph Recall Scores. |
| NCT02912364 (5) [back to overview] | Overall Composite Z Score of Neuropsychological Battery as a Measure of Direct Comparison of the 2 Antiepileptic Drugs. |
| NCT02912364 (5) [back to overview] | Dual Task Percent of Time in Box. |
| NCT02912364 (5) [back to overview] | Overall Z-score for Executive Function. |
| NCT03116828 (1) [back to overview] | The Number of Subjects Completing 24 Weeks Adjunctive Therapy During Maintenance Phase |
Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.
Seizure-free subjects during the last four weeks of monotherapy were determined as subjects who had seizure assessments during the 4 weeks between Visits 8 and 9 (Weeks 15 through 18), and did not have any seizures. (NCT00866775)
Timeframe: Weeks 15 through 18
| Intervention | percentage of participants (Number) |
|---|
| Eslicarbazepine 1200 mg QD | 13.3 |
| Eslicarbazepine 1600 mg QD | 14.4 |
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
(NCT00866775)
Timeframe: 18 Week Double-blind treatment period
| Intervention | Percent of participants (Number) |
|---|
| Actual Attempt | Non-suicidal Self-Injurious Behavior | Interrupted Attempt | Aborted Attempt | Preparatory Attempts | SuicidalBehavior | Wish to be Dead | Non-specific Active Suicidal Thoughts | Act. Suicidal Idea. w/any method-no intent to act | Act. Suicidal Idea.w/any method-some intent to act | Act. Suicidal Idea. w/any method-Spec. Plan to act |
|---|
| Eslicarbazepine 1200 mg QD | 0 | 0 | 1.5 | 0 | 1.5 | 0 | 4.6 | 4.6 | 1.5 | 0 | 0 |
,| Eslicarbazepine 1600 mg QD | 0 | 0 | 0 | 0 | 0 | 0 | 3.1 | 0.8 | 0.8 | 0 | 0 |
Percentage of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.
Seizure-free subjects during the monotherapy period were determined as subjects who had seizure assessments during the monotherapy period, and did not have any seizures in the 10 weeks between Visits 6 and 9 (Weeks 9 through 18). Subjects who discontinued during this period were considered not seizure-free even if they were seizure-free at the time of discontinuation, i.e., to be considered seizure-free, subjects must complete the 10-week period without any seizures. (NCT00866775)
Timeframe: Weeks 9 through 18
| Intervention | percentage of participants (Number) |
|---|
| Eslicarbazepine 1200 mg QD | 8.3 |
| Eslicarbazepine 1600 mg QD | 7.6 |
Percentage of Subjects With Increase of Body Weight >= 7%
(NCT00866775)
Timeframe: 18 Week Double-blind treatment period
| Intervention | Percentage of participants (Number) |
|---|
| Eslicarbazepine 1200 mg QD | 2 |
| Eslicarbazepine 1600 mg QD | 9 |
Percentage of Subjects Reaching Each of the Exit Events.
The percentage of subjects reaching each of the 5 exit criteria. 1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator. (NCT00866775)
Timeframe: Week 1 to Week 18
| Intervention | percentage of participants (Number) |
|---|
| exit criterion 1 | exit criterion 2 | exit criterion 3 (investigator prog. assessment) | exit criterion 3 (sponsors prog. assessment) | exit criterion 4 (investigaor prog. assessment) | exit criterion 4 (sponsor prog. assessment) | exit criterion 5 |
|---|
| Eslicarbazepine 1200 mg QD | 0 | 6.7 | 10.0 | 8.3 | 8.3 | 10.0 | 13.3 |
,| Eslicarbazepine 1600 mg QD | 0.8 | 0.8 | 4.2 | 5.9 | 5.1 | 5.9 | 3.4 |
Time on Eslicarbazepine Acetate Monotherapy.
The start of the monotherapy period was defined as the date of termination of all other AEDs while taking study monotherapy medication. Time on monotherapy was defined from the start of monotherapy period to the last dose of monotherapy treatment. (NCT00866775)
Timeframe: Week 8 to Week 18
| Intervention | days (Median) |
|---|
| Eslicarbazepine 1200 mg QD | NA |
| Eslicarbazepine 1600 mg QD | NA |
Change in Total Score From Baseline in MADRS in Those Subjects With a MADRS Score of ≥14 at Randomization.
The total score of MADRS is defined as the sum of all individual symptom scores, ranging from 0 to 60, higher score indicates more severe depression. Each of the 10 symptoms of depression on MADRS was measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity (NCT00866775)
Timeframe: Week 0 to Week 18, Baseline: Day 0; End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
| Intervention | units on a scale (Mean) |
|---|
| Change from baseline to AED T/C pd n=7,13 | Change from baseline to end of mono pd n=6,13 |
|---|
| Eslicarbazepine 1200 mg QD | -1.3 | -6.8 |
,| Eslicarbazepine 1600 mg QD | -7.9 | -9.6 |
Change in Seizure Frequency From Baseline.
The relative (%) change in standardized seizure frequency was evaluated for four periods: titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18). (NCT00866775)
Timeframe: Week 0 to Week 18, Double-blind: weeks 1to 18; baseline:weeks-8 to -1; Titration: weeks 1 to 2; AED taper/conversion:weeks 3 to 8; monotherapy: weeks 9 to 18
| Intervention | percent change (Median) |
|---|
| Relative (%) change from baselne for DB period | Relative (%) change from baseline -tiration period | Relative (%) change from baseline -AED t/c period | Relative (%) change from baseline - mono period |
|---|
| Eslicarbazepine 1200 mg QD | -30.9 | -29.6 | -30.2 | -48.7 |
,| Eslicarbazepine 1600 mg QD | -41.5 | -52.4 | -39.7 | -38.6 |
Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).
The QOLIE-31 overall score was obtained by using a weighted average of multi-item scale scores. The recorded responses were converted to 0-100 point scales. The mean of the individual item scores in each subgroup were calculated, with higher converted scores reflecting better quality of life. (NCT00866775)
Timeframe: Week 0 to Week 18, baseline: day 0: End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
| Intervention | units on a scale (Mean) |
|---|
| Change from baseline to end of AED T/C pd n=39,86 | change from baseline to end of mono. pd n=36,86 |
|---|
| Eslicarbazepine 1200 mg QD | 3.2 | 7.8 |
,| Eslicarbazepine 1600 mg QD | 6.3 | 6.4 |
Completion Rate
Subjects completing the study were determined as subjects who completed the 18 weeks of double-blind treatment. (NCT00866775)
Timeframe: Week 1 to Week 18
| Intervention | percentage of participants (Number) |
|---|
| Eslicarbazepine 1200 mg QD | 48.3 |
| Eslicarbazepine 1600 mg QD | 64.4 |
Completion Rate During the 10 Weeks of Monotherapy
Monotherapy completion rate was defined as the proportion (%) of subjects entering the monotherapy period who completed the 10 weeks of monotherapy treatment. (NCT00866775)
Timeframe: Weeks 8 through 18
| Intervention | percentage of participants (Number) |
|---|
| Eslicarbazepine 1200 mg QD | 64.4 |
| Eslicarbazepine 1600 mg QD | 81.7 |
Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method
Cumulative exit rate was defined as the proportion of subjects meeting at least one of the five exit criteria over a 16-wk study period (start of Antiepilectic Drugs(AED) taper/conv.period (Wk 3 to end of double blind monotherapy period (Wk 18)):1.One episode of status epilepticus.2.One secondary general partial seizure (in subjects who did not have gen. seizures during 6 months prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 wk baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 wk baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 wk baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the Investigator. (NCT00866775)
Timeframe: Week 3 to Week 18
| Intervention | proportion of participants (Number) |
|---|
| Eslicarbazepine 1200 mg QD | 0.444 |
| Eslicarbazepine 1600 mg QD | 0.287 |
Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS).
The total score of MADRS is defined as the sum of all individual symptom scores, ranging from 0 to 60, higher score indicates more severe depression. Each of the 10 symptoms of depression on MADRS was measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity (NCT00866775)
Timeframe: Week 0 to Week 18; Baseline: day 0; End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
| Intervention | units on a scale (Mean) |
|---|
| Change from baseline to AED T/C period | Change from baseline to end of mono period |
|---|
| Eslicarbazepine 1200 mg QD | -0.4 | -1.1 |
,| Eslicarbazepine 1600 mg QD | -2.0 | -2.4 |
Standardized Seizure Frequency (SSF) by Period
Seizure frequency was evaluated by using a standardized frequency per 4 weeks (28 days). It was evaluated for five periods: baseline (Weeks -8 to -1), titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18). (NCT00866775)
Timeframe: Week 1 to Week 18, Double-blind: weeks 1 to 18; Baseline: weeks -8 to -1; Titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; Monotherapy: weeks 9 to 18
| Intervention | Number of seizures in 28 days (Mean) |
|---|
| SSF during double-blind period | SSF during baseline | SSF during titration period | SSF during AED taper/conversion period | SSF during monotherapy period |
|---|
| Eslicarbazepine 1200 mg QD | 8.8 | 8.7 | 6.2 | 8.7 | 13.2 |
,| Eslicarbazepine 1600 mg QD | 6.9 | 10.9 | 6.4 | 6.9 | 6.8 |
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Responder rate was defined as the proportion (%) of subjects with a ≥ 50% reduction of seizure frequency from baseline. This analysis was done for the titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18) periods. (NCT00866775)
Timeframe: Week 0 to Week 18, Double blind: weeks to 8; baseline:weeks -8 to -1; titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; monotherapy: weeks 9 to 18
| Intervention | percentage of participants (Number) |
|---|
| Responder rate during double blind period | Responder rate during the titration period | Responder Rate during the AED T/C period | Responder rate during monotherapy period |
|---|
| Eslicarbazepine 1200 mg QD | 36.7 | 46.7 | 41.7 | 35.0 |
,| Eslicarbazepine 1600 mg QD | 39.8 | 51.7 | 43.2 | 32.2 |
Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L
Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L (NCT00866775)
Timeframe: 18 Week Double-blind treatment period
| Intervention | Percent (Number) |
|---|
| ≤ 135 and > 130 mEq/L | ≤ 13- amd > 125 mEq/L | ≤125 mEq/L |
|---|
| Eslicarbazepine 1200 mg QD | 29 | 6 | 3 |
,| Eslicarbazepine 1600 mg QD | 61 | 11 | 5 |
Cmax - Maximum Observed Plasma Concentration
To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel). (NCT00898560)
Timeframe: 15-day
| Intervention | pg/mL (Mean) |
|---|
| Cmax (ethinyloestradiol) | Cmax (levonogestrel) |
|---|
| ESL and Microginon® | 75.0 | 4340 |
,| Microginon® | 82.4 | 4170 |
AUC0-t - Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification
To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel). (NCT00898560)
Timeframe: 15-day
| Intervention | ng.h/mL (Mean) |
|---|
| AUC0-t (ethinyloestradiol) | AUC0-t (levonogestrel) |
|---|
| ESL and Microginon® | 0.453 | 32.0 |
,| Microginon® | 0.665 | 37.4 |
AUC0-∞ - Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity
To investigate whether multiple-dose administration of eslicarbazepine acetate (ESL, BIA 2-093) 800 mg once-daily (QD) affects the pharmacokinetics of the components of a combined oral contraceptive (ethinyloestradiol and levonorgestrel). (NCT00898560)
Timeframe: 15-day
| Intervention | ng.h/mL (Mean) |
|---|
| AUC0-∞ (ethinyloestradiol) | AUC0-∞ (levonorgestrel) |
|---|
| ESL and Microginon® | 0.533 | 43.1 |
,| Microginon® | 0.768 | 52.1 |
Cmax - Maximum Plasma Concentration in Plasma and Cerebral Spinal Fluid
Cmax - Maximum plasma concentration CSF - Cerebral Spinal Fluid Oxcarbazepine, BIA 2-194 and BIA 2-195 are active metabolites of Eslicarbazepine Acetate. (NCT00900237)
Timeframe: Day 9 - Pre-dose; 0.5h; 1h; 1.5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h; 24h
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-194) plasma | Cmax (BIA 2-195) plasma | Cmax (Oxcarbazepine) plasma | Cmax (BIA 2-194) CSF | Cmax (BIA 2-195) CSF | Cmax (Oxcarbazepine) CSF |
|---|
| Eslicarbazepine Acetate | 23932 | 886 | 245 | 7559 | 538 | 93.2 |
,| Oxcarbazepine | 16162 | 4039 | 1990 | 7566 | 2146 | 448 |
AUC0-t AUC From Time Zero to the Last Sampling Time
AUC0-t - area under the concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification CSF - cerebrospinal fluid Oxcarbazepine, BIA 2-194 and BIA 2-195 are active metabolites of Eslicarbazepine Acetate. (NCT00900237)
Timeframe: Day 9 - Pre-dose; 0.5h; 1h; 1.5h; 2h; 3h; 4h; 6h; 8h; 12h; 16h; 24h
| Intervention | ng.h/mL (Mean) |
|---|
| AUC0-t (BIA 2-194) plasma | AUC0-t (BIA 2-195) plasma | AUC0-t (Oxcarbazepine) plasma | AUC0-t (BIA 2-194) CSF | AUC0-t (BIA 2-195) CSF | AUC0-t (Oxcarbazepine) CSF |
|---|
| Eslicarbazepine Acetate | 340123 | 18743 | 3377 | 154509 | 11791 | 1522 |
,| Oxcarbazepine | 164726 | 39034 | 7135 | 86187 | 23996 | 2485 |
Number and Percent of Subjects With Treatment Emergent Adverse Events
Number and percent of subjects with treatment emergent adverse events (NCT00910247)
Timeframe: One year
| Intervention | Participants (Count of Participants) |
|---|
| Eslicarbazepine Acetate | 220 |
Number and Percentage of Subjects With Orthostatic Effects.
Number and percentage of subjects with orthostatic effects. (NCT00910247)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Eslicarbazepine Acetate | 67 |
Number and Percentage of Subjects With Potentially Clinically Significant Clinical Laboratory Evaluations
Number and percentage of subjects with potentially clinically significant clinical laboratory evaluations (NCT00910247)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Eslicarbazepine Acetate | 186 |
Percentage of Subjects That Are Seizure-free During Study
Percentage of subjects that are seizure-free during study (NCT00910247)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Eslicarbazepine Acetate | 7.3 |
Percentage of Subjects With Increase of Body Weight ≥7%
Percentage of subjects with increase of body weight ≥7% (NCT00910247)
Timeframe: 1 year
| Intervention | percentagae of participants (Number) |
|---|
| Eslicarbazepine Acetate | 27 |
Responder Rate (Percentage of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Responder rate (percentage of subjects with a ≥50% reduction of seizure frequency from baseline). (NCT00910247)
Timeframe: One year
| Intervention | percentage of participants (Number) |
|---|
| Eslicarbazepine Acetate | 62.4 |
Time on Eslicarbazepine Acetate Monotherapy.
The start of the monotherapy period was defined as the date of termination of all other anti-epileptic drugs while taking study medication. Time on eslicarbazepine acetate monotherapy is defined from the date of the first monotherapy dose in 093-045 or 093-046 study to the last known dose of monotherapy treatment, regardless of dose change and the time gap between the parent studies and the current study. (NCT00910247)
Timeframe: One year
| Intervention | Days (Median) |
|---|
| Eslicarbazepine Acetate | NA |
Treatment Retention Time (Time to Withdrawal Due to Lack of Efficacy or Adverse Events)
The retention time is defined from the start of eslicarbazepine acetate monotherapy period in 093-045 or 093-046 to the last known dose of open-label eslicarbazepine acetate. The time may include taking eslicarbazepine acetate concomitantly with other anti-epileptic drugs. If a subject's termination reason(s) includes: withdrawal of consent, lost to follow-up, physician decision or other, then it was assumed the subject terminated the study due to lack of efficacy. (NCT00910247)
Timeframe: One year
| Intervention | days (Median) |
|---|
| Eslicarbazepine Acetate | NA |
Number and Percentage of Subjects With QTc-F Changes (in Categories) From Baseline.
"Number and percentage of subjects by QT interval corrected using the Fridericia fomula (QTcF) categories~Based on the numbers of subjects who had at least one post-baseline assessment, the number and percentage of subjects with QTcF values in the following categories were summarized:~>500 millisecond (msec) at any post-baseline timepoint but not present at baseline~>480 msec at any post-baseline timepoint but not present at baseline~>450 msec at any post-baseline timepoint but not present at baseline~Change from Baseline >=60 ms for at least one post-baseline measurement~Change from Baseline >=30 ms for at least one post-baseline measurement and <60 ms for all post-baseline measurement~QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle." (NCT00910247)
Timeframe: Baseline, Month 12
| Intervention | Participants (Count of Participants) |
|---|
| >500ms at any postbaseline not present at baseli | >450ms at any postbaseline not present at baseline | >480ms at any postbaseline not present at baseline | CFB >=60 ms for at least one post-baseline | CFB>=30ms for at least one &<60ms for all PBL |
|---|
| Eslicarbazepine Acetate | 0 | 9 | 1 | 0 | 42 |
Percentage of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
"The C-SSRS is an instrument designed to systematically assess and track suicidal behavior and suicidal ideation. The C-SSRS will be completed by the Investigator or Sub-Investigator (or qualified site personnel).~Suicidal ideation is collected as any occurrence of wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intent to act, active suicidal ideation with some intent to act, without specific plan, active suicidal ideation with specific plan and intent.~Suicidal behavior is collected as any occurrence of actual attempts, Non-Suicidal Self-Injurious Behavior, interrupted attempts, aborted attempts, or preparatory acts or behavior, suicidal behavior.~Any suicidality is defined as having at least one occurrence of Suicidal Behavior or Suicidal Ideation." (NCT00910247)
Timeframe: 1 year
| Intervention | percentage of events (Number) |
|---|
| Any Suicidality | Any suicidal behavior | Any suicidal ideation |
|---|
| Eslicarbazepine Acetate | 4.0 | 0.7 | 3.6 |
Number and Percent of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L
Number and percentage of subjects who had normal sodium value (i.e. >135 mEq/L) at baseline but reached <=135 mEq/L and >130 mEq/L, <=130 mEq/L and >125 mEq/L, or <=125 mEq/L at any post baseline. (NCT00910247)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| <=135 mEq/L and >130 mEq/L | <=130 mEq/L and >125 mEq/L | <=125 mEq/L |
|---|
| Eslicarbazepine Acetate | 48 | 22 | 4 |
Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) in Those Subjects With a MADRS Score of ≥14 at Screening
The total score of MADRS is defined as the sum of all individual item scores . Each of the 10 symptoms of depression on MADRS is measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity. (NCT00910247)
Timeframe: baseline and Month 12
| Intervention | units on a scale (Mean) |
|---|
| Eslicarbazepine Acetate | -1.5 |
Change in Seizure Frequency From Baseline.
Relative (%) change in standard seizure frequency(SSF) from baseline (NCT00910247)
Timeframe: Month 12 from baseline
| Intervention | percent change (Median) |
|---|
| Eslicarbazepine Acetate | -66.4 |
Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).
"Change in the overall score from baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31 )~The QOLIE-31 overall score was obtained by using a weighted average of multi-item scale scores. The recorded responses were converted to 0-100 point scales. The mean of the individual item scores in each subgroup were calculated, with higher converted scores reflecting better quality of life." (NCT00910247)
Timeframe: baseline and Month 12
| Intervention | units on a scale (Mean) |
|---|
| Eslicarbazepine Acetate | 6.6 |
Change in Total Score From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS).
The total score of MADRS is defined as the sum of all individual item scores. Each of the 10 symptoms of depression on MADRS is measured on a scale of 0 to 6 with 0 representing the lowest severity of the symptom and 6 representing the highest severity. (NCT00910247)
Timeframe: 1 year
| Intervention | units on a scale (Mean) |
|---|
| Eslicarbazepine Acetate | -1.5 |
Completion Rate (% of Subjects Completing Each Visit Post-one Year).
Completion rate (% of subjects completing each visit post-one year). (NCT00910247)
Timeframe: post 1 year
| Intervention | percentagae of participants (Number) |
|---|
| Eslicarbazepine Acetate | 66.7 |
Completion Rate (% of Subjects Completing the One Year Treatment)
Completion rate (% of subjects completing the one year treatment) (NCT00910247)
Timeframe: One year
| Intervention | percentagae of participants (Number) |
|---|
| Eslicarbazepine Acetate | 74.8 |
PART I - Seizure Frequency
The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the ITT population. Efficacy analyses were performed chiefly using data from the 12-week maintenance period in Part I of the study. The primary efficacy variable is the ln transformation of the seizure frequency per 4 weeks. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA that models seizure frequency as a function of baseline seizure frequency and treatment. (NCT00957047)
Timeframe: 12-week maintenance period
| Intervention | ln (Seizures) per 4 weeks (Least Squares Mean) |
|---|
| ESL 1200 mg Once Daily | 7 |
| ESL 400 mg Once Daily | 8.7 |
| ESL 800 mg Once Daily | 7.1 |
| Placebo | 9.8 |
PART II - Nº of Treatment-Emergent Adverse Events (TEAE)
Safety assessments were based primarily on AEs (Number of patients who experienced at least one AEs), and on whether these were related to the study medication, were serious, led to permanent discontinuation of study participation, or led to death. (NCT00957047)
Timeframe: 1 year
| Intervention | participants (Number) |
|---|
| TEAE | 270 |
| TEAE With Onset Within the 1st 4 Weeks | 151 |
| TEAE With Onset After 1st 4 Weeks | 240 |
| Treatment-related TEAE | 194 |
| TEAE Leading to Discontinuation | 37 |
| Serious TEAE | 28 |
| TEAE Leading to Death | 3 |
PART II: Nº of Treatment-Emergent Adverse Events (TEAE)
The primary objective for Part II of the study was to evaluate the safety and tolerability of eslicarbazepine acetate (ESL, BIA 2-093) at doses titrated to an efficacy or safety endpoint over a 1-year open-label period. Safety assessments were based primarily on AEs (Number of participants with at least one treatment-emergent adverse events are reported); assessment of AEs was based on treatment relatedness, action taken on study drug, outcome, and causality. (NCT00957372)
Timeframe: 1-year
| Intervention | participants (Number) |
|---|
| TEAE | 112 |
| TEAE With Onset Within the First 4 Weeks of Part II | 40 |
| TEAE With Onset After the First 4 Weeks of Part II | 94 |
| Treatment-related Treatment-emergent Adverse Event | 66 |
| TEAE Leading to Discontinuation From the Study | 9 |
| Treatment Emergent Serious Adverse Event | 11 |
| TEAE Leading to Death | 2 |
Seizure Frequency
The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on results for the ITT population during the 12-week maintenance period. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA model with treatment as a factor and seizure frequency as a covariate (NCT00957372)
Timeframe: 12 weeks
| Intervention | ln (Seizures) per 4 weeks (Least Squares Mean) |
|---|
| Placebo | 7.3 |
| ESL 800 mg | 5.7 |
| ESL 1200 mg | 5.5 |
Part I: Seizure Frequency
"The primary efficacy endpoint is the natural log transformation of the seizure frequency per 4 weeks. The primary efficacy analysis was based on the intention-to-treat (ITT) population. Efficacy analyses were performed chiefly using data from the 12-week maintenance period in Part I of the study. The primary efficacy variable is the ln transformation of the seizure frequency per 4 weeks. Seizure frequency was compared between each active treatment group and the placebo group using an ANCOVA that models seizure frequency as a function of baseline seizure frequency and treatment.to a frequency per 4 weeks basis" (NCT00957684)
Timeframe: 12-week maintenance period
| Intervention | ln (Seizures) per 4 weeks (Least Squares Mean) |
|---|
| Placebo | 7.64 |
| ESL 400 mg | 6.73 |
| ESL 800 mg | 5.66 |
| ESL 1200 mg | 5.35 |
AUC0-∞ - Area Under the Plasma Concentration From Time Zero to Infinity
area under the plasma metformin concentration from time zero to infinity (NCT00971295)
Timeframe: 3 weeks
| Intervention | ng*h/mL (Mean) |
|---|
| Metformin + ESL | 7362 |
| Metformin | 7688 |
Cmax - Maximum Observed Plasma Concentration
Maximum Observed Plasma Metformin Concentration (NCT00971295)
Timeframe: 3 weeks
| Intervention | ng/mL (Mean) |
|---|
| Metformin + ESL | 1091 |
| Metformin | 1224 |
Tmax - Time of Occurrence of Cmax
time of occurrence of maximum observed plasma metformin concentration (NCT00971295)
Timeframe: 3 weeks
| Intervention | hours (Mean) |
|---|
| Metformin + ESL | 2.66 |
| Metformin | 2.53 |
Change From Baseline to Endpoint in Mean Pain, Scored Daily on a on an 11-point (0-10) Numeric Rating Pain Scale (NRPS), Where 0 = no Pain and 10 = Worst Possible Pain
Endpoint mean pain was defined as the mean of the last 4 available pain scores in the last 7 days of the treatment period. Likewise, baseline mean pain was defined as the mean of the last 4 available pain scores in the last 7 days of the baseline period. (NCT00980746)
Timeframe: 17 weeks
| Intervention | units on a scale (Least Squares Mean) |
|---|
| ESL 1200 mg QD | -1.7546 |
| ESL 400 mg BD | -2.2865 |
| ESL 600 mg BID | -1.6746 |
| ESL 800 mg BID | -1.8353 |
| ESL 800 mg QD | -1.9829 |
| Placebo | -1.5801 |
Change in Mean Pain (NRPS) From Baseline to Endpoint by Total Daily Dose
"Details of neuropathic pain, as recorded in a subject diary, were used for the primary assessment of analgesic efficacy. Subjects assessed their pain using an 11-point (0 no pain to 10 worst possible pain) NRPS upon awakening each morning and recorded the results in the subject diary. This score reflected the subject's mean pain over the previous 24 hours. Subjects were trained how to record their pain reliably. Investigators were trained in the subject's NRPS use during site initiation visits and at the investigators' meeting." (NCT00981227)
Timeframe: baseline and 13 weeks
| Intervention | Points (Least Squares Mean) |
|---|
| Placebo | -1.5448 |
| ESL 1200 mg/Day | -1.8183 |
| ESL 1600 mg/Day | -2.0854 |
| ESL 800 mg/Day | -1.8236 |
Change in Mean Pain (NRPS) From Baseline to Endpoint in Mean Pain
"The primary efficacy variable will be based upon an 11-point (0-10) Numeric Rating Pain Scale (NRPS), where 0 = no pain and 10 = worst possible pain, to be recorded in a patient's diary upon awakening each morning. This score should reflect the patient's mean pain over the previous 24 hours.~Please note that the change from baseline to endpoint in mean pain, i.e. the difference between endpoint mean pain and baseline mean pain, which are defined as follows:~Baseline mean pain is defined as the mean of the last four available ratings of average daily pain (NRPS) in the patient diary performed in the last 7 days before randomisation.~Endpoint mean pain is defined as the mean of the last four available ratings of average daily pain in the patient diary in the last 7 days of the treatment period." (NCT00981227)
Timeframe: baseline and 13 weeks
| Intervention | Points (Least Squares Mean) |
|---|
| ESL 1200 mg Once Daily | -1.9447 |
| ESL 400 mg Twice-daily | -1.9786 |
| ESL 600 mg Twice Daily | -1.6798 |
| ESL 800 mg Once-daily | -1.6633 |
| ESL 800 mg Twice Daily | -2.0834 |
| Placebo | -1.5441 |
Simvastatin Tmax (Time of Occurrence of Cmax)
Simvastatin (Reference) ESL + Simvastatin (Test) (NCT00987558)
Timeframe: Day 1 and Day 14
| Intervention | hours (Mean) |
|---|
| Simvastatin (Reference) | 1.50 |
| ESL + Simvastatin (Test) | 1.62 |
Simvastatin AUC0-∞ (AUC From Time Zero to Infinity)
Simvastatin (Reference) ESL + Simvastatin (Test) (NCT00987558)
Timeframe: Day 1 and Day 14
| Intervention | ng.h/mL (Mean) |
|---|
| Simvastatin (Reference) | 108 |
| ESL + Simvastatin (Test) | 54.6 |
Simvastatin Cmax (Maximum Plasma Concentration)
Simvastatin (Reference) ESL + Simvastatin (Test) (NCT00987558)
Timeframe: Day 1 and Day 14
| Intervention | ng/mL (Mean) |
|---|
| Simvastatin (Reference) | 17.7 |
| ESL + Simvastatin (Test) | 6.89 |
Simvastatin AUC0-t
"AUC0-t - area under the plasma concentration versus time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the limit of quantification~Simvastatin (Reference) ESL + Simvastatin (Test)" (NCT00987558)
Timeframe: Day 1 and Day 14
| Intervention | ng.h/mL (Mean) |
|---|
| Simvastatin (Reference) | 93.9 |
| ESL + Simvastatin (Test) | 43.3 |
Change From Baseline in Seizure Frequency
Relative reduction in the standardised 4-week seizure frequency from the baseline period to the 12-week maintenance period. (NCT00988156)
Timeframe: Baseline up to Visit 7
| Intervention | seizures/month (Mean) |
|---|
| Placebo | 62.0 |
| Esl (BIA 2-093) | 36.6 |
Responder Rate
Responder rate defined as the number of patients with at least a 50% decrease in the standardised 4-week seizure frequency from the baseline period to the 12-week maintenance period. (NCT00988156)
Timeframe: baseline up to Visit 7
| Intervention | participants (Number) |
|---|
| Placebo | 40 |
| Esl (BIA 2-093) | 41 |
Proportion of Responders
Subjects who had at least a 50% reduction from baseline in standardized seizure frequency during the maintenance period were classified as responders. (NCT00988429)
Timeframe: Baseline (Week-8 through Week -1) and Maintenance period (Week 3 to week 14)
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 23.1 |
| ESL 800 mg QD (ITT Population) | 30.5 |
| ESL 1200 mg QD (ITT Population) | 42.6 |
Seizure Frequency Over the 12-week Maintenance Period.
(NCT00988429)
Timeframe: 12-week maintenance period (Week 3 to week 14)
| Intervention | Nº Standardized Seizures by 4 weeks (Least Squares Mean) |
|---|
| Placebo (ITT Population) | 7.88 |
| ESL 800 mg QD (ITT Population) | 6.54 |
| ESL 1200 mg QD (ITT Population) | 6.00 |
Cumulative 112-day Exit Rate as Estimated by Kaplan-Meier Method
"Cumulative exit rate was defined as the proportion of subjects meeting at least one of the following five exit criteria over a 16-week study period (from start of AED taper/con. period (Wk 3) to end of double blind monotherapy period (Wk 18)).1.One episode of status epilepticus.2.One secondary gen. partial seizure (in subjects who did not have gen.seizures during 6 mo. prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 week baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 week baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 week baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.~5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the investigator" (NCT01091662)
Timeframe: From beginning of Week 3 to end of Week 18
| Intervention | proportion of participants (Number) |
|---|
| ESL1200 mg | 0.156 |
| ESL 1600 mg | 0.128 |
Percentage of Subjects Seizure-free During the Last 4 Weeks on Eslicarbazepine Acetate Monotherapy.
Percentage of participants that were Seizure-free during the last four weeks of monotherapy were determined as subjects who had seizure assessments during the 4 weeks between Visits 8 and 9 (Weeks 15 through 18), and did not have any seizures. (NCT01091662)
Timeframe: Week 15 through 18
| Intervention | percentage of participants (Number) |
|---|
| ESL1200 mg | 16.7 |
| ESL 1600 mg | 17.0 |
Proportion (%) of Subjects With Increase of Body Weight >= 7% From Baseline
(NCT01091662)
Timeframe: 18 Week Double-blind treatment period
| Intervention | percentage of participants (Number) |
|---|
| ESL1200 mg | 1.8 |
| ESL 1600 mg | 11.7 |
Time on Eslicarbazepine Acetate Monotherapy.
The start of the monotherapy period was defined as the date of termination of all other AEDs while taking study monotherapy medication. Time on monotherapy was defined from the start of monotherapy period to the last dose of monotherapy treatment. (NCT01091662)
Timeframe: Week 8 to Week 18
| Intervention | days (Median) |
|---|
| ESL1200 mg | NA |
| ESL 1600 mg | NA |
Change in Seizure Frequency From Baseline.
The relative (%) change in standardized seizure frequency was evaluated for four periods: titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18). (NCT01091662)
Timeframe: 18 weeks, Double-blind:weeks 1-18; Baseline: weeks -8to -1; titration: weeks 1 to 2; AED taper/conversion: weeks 3 to 8; monotherapy; weeks 9 to 18
| Intervention | Percent change (Median) |
|---|
| Relative(%) change from baseline fo DB pd n=54,98 | Relative(%)chg from baseline for titrat pd n=54,98 | Relative (%) chg from baseline-AED t/c pd n=54,98 | Relative (%) change from baseline-mono pd n=48,87 |
|---|
| ESL 1200 mg | -36.1 | -19.3 | -39.4 | -45.7 |
,| ESL 1600 mg | -47.5 | -35.6 | -42.9 | -52.1 |
Change in Total Score From Baseline in 31-Item Quality of Life in Epilepsy (QOLIE-31).
The QOLIE-31 overall score was obtained by using a weighted average of multi-item scale scores. The recorded responses were converted to 0-100 point scales. The mean of the individual item scores in each subgroup were calculated, with higher converted scores reflecting better quality of life. (NCT01091662)
Timeframe: Week 0 to Week 18, Baseline: Day 0: End of AED taper/conversion period: end of week 8; End of monotherapy period: end of week 18
| Intervention | units on a scale (Mean) |
|---|
| chg from baseline-end of AED taper/covn.pd n=45,85 | change from baseline-end of monotherapy pd n=50,96 |
|---|
| ESL 1600 mg | 5.8 | 4.7 |
,| ESL1200 mg | 3.4 | 4.0 |
Standardized Seizure Frequency (SSF) by Period
Seizure frequency was evaluated by using a standardized frequency per 4 weeks (28 days). It was evaluated for five periods: baseline (Weeks -8 to -1), titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18). (NCT01091662)
Timeframe: Double-blind: week to 18; Baseline: weeks -8 to -1; titration: weeks 1 to 2; AED taper/conversion weeks 3 to 8; monotherapy: weeks 9 to 18
| Intervention | seizures in 28 days (Mean) |
|---|
| SSF during double-blind pd n=54,100 | SSF druing baseline pd n=54,98 | SSF during titration pd n=54,100 | SSF during AED taper/conversion pd n=54,100 | SSF during monotherapy pd n=48,88 |
|---|
| ESL 1600 mg | 5.2 | 8.7 | 6.4 | 5.1 | 5.0 |
,| ESL1200 mg | 5.5 | 7.4 | 6.0 | 6.0 | 4.7 |
Responder Rate (Proportion [%] of Subjects With a ≥50% Reduction of Seizure Frequency From Baseline).
Responder rate was defined as the proportion (%) of subjects with a ≥ 50% reduction of seizure frequency from baseline. This analysis was done for the titration (Weeks 1 to 2), AED taper/conversion (Weeks 3 to 8), monotherapy (Weeks 9 to 18), and double-blind (Weeks 1 to 18) periods. (NCT01091662)
Timeframe: Week 0 to Week 18, Double-blind weeks 1-18; baseline: weeks -8 to -1; Titration: weeks 1-2; AED taper/conversion; weeks 3-8; monotherapy weeks 9-18
| Intervention | percentage of participants (Number) |
|---|
| responder rate during the DB period | responder rate during titration period | responder rate during the AED | responder rate during monotherapy period |
|---|
| ESL 1600 mg | 46.0 | 37.0 | 39.0 | 46.0 |
,| ESL1200 mg | 35.2 | 29.6 | 29.6 | 38.9 |
Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L.
Proportion (%) of Subjects With Normal Baseline Sodium Reaching Blood Sodium ≤135 mmol/L, ≤130 mmol/L, and ≤125 mmol/L (NCT01091662)
Timeframe: Week 0 to Week 18
| Intervention | percentage of participants (Number) |
|---|
| ≤ 135 and > 130 mEq/L | ≤ 130 and > 125 mEq/L | ≤ 125 mEq/L |
|---|
| ESL 1600 mg | 54.5 | 20.9 | 0 |
,| ESL1200 mg | 49.1 | 8.8 | 0 |
Proportion (%) of Subjects Reaching Each Exit Criteria
"The proportion (%) of subjects reaching each of the 5 exit criteria-1.One episode of status epilepticus.2.One secondary gen. partial seizure (in subjects who did not have gen.seizures during 6 mo. prior to screening).3.A two fold increase in any consecutive 28 day seizure rate compared to the highest consecutive 28 day seizure rate during the 8 week baseline period. 4.A two fold increase in any consecutive 2 day seizure rate compared to the highest consecutive 2 day seizure rate during the 8 week baseline period. If the highest number of seizures in any consecutive 2 day period during the 8 week baseline was 1 then 3 seizures in a consecutive 2 day period was required to exit.~5.Worsening of seizures or increase in seizure frequency considered serious or requiring intervention as judged by the investigator" (NCT01091662)
Timeframe: Week 1 to Week 18, (beginning of week 1 to end of week 18)
| Intervention | percentage of participants (Number) |
|---|
| exit criterion 1 | exit criterion 2 | exit criterion investigator prog. assessment) | exit criterion 3 (sponsors prog. assessment) | exit criterion 4 (investigaor prog. assessment) | exit criterion 4 (sponsor prog. assessment) | exit criterion 5 |
|---|
| ESL 1600 mg | 0 | 0 | 2.0 | 1.0 | 5.0 | 6.0 | 5.0 |
,| ESL1200 mg | 0 | 1.9 | 5.6 | 3.7 | 1.9 | 3.7 | 3.7 |
Proportion (%) of Subjects That Are Seizure-free During the 10-week Double-blind Monotherapy Treatment Period.
Seizure-free subjects during the monotherapy period were determined as subjects who had seizure assessments during the monotherapy period, and did not have any seizures in the 10 weeks between Visits 6 and 9 (Weeks 9 through 18). Subjects who discontinued during this period were considered not seizure-free even if they were seizure-free at the time of discontinuation, i.e., to be considered seizure-free, subjects must complete the 10-week period without any seizures. (NCT01091662)
Timeframe: Week 9 through 18
| Intervention | percentage of participants (Number) |
|---|
| ESL1200 mg | 7.4 |
| ESL 1600 mg | 10.0 |
Proportion (%) of Events in Each Classification of the Columbia Suicide Severity Rating Scale (C SSRS).
(NCT01091662)
Timeframe: 18 Week Double-blind treatment period
| Intervention | Percent of particiants (Number) |
|---|
| Actual Attempt | Non-suicidal Self-Injurious Behavior | Interrupted Attempt | Aborted Attempt | Preparatory Attempts | Suicidal Behavior | Wish to be Dead | Non-specific Active Suicidal Thoughts | Act. Suicidal Idea. w/any method-no intent to act | Act. Suicidal Idea.w/any method-some intent to act | Act. Suicidal Idea. w/any method-Spec. Plan to act |
|---|
| ESL 1600 mg | 0 | 0.9 | 0 | 0 | 0 | 0 | 0.9 | 1 | 0 | 0.9 | 0 |
,| ESL1200 mg | 3.4 | 0 | 0 | 0 | 0 | 3.4 | 1.7 | 0 | 0 | 0 | 0 |
Change in Total Score of MADRS From Baseline in Those Subjects With a MADRS Score of ≥14 at Randomization.
The total score of MADRS is defined as the sum of all individual item scores. From 0-60, higher score indicates more severe (NCT01091662)
Timeframe: Week 0 to Week 18, baseline:day 0;end of AED taper/conversion period; end of week 8; end of monotherapy period: end of week 18
| Intervention | units on a scale (Mean) |
|---|
| chge from baseline-end of AED taper/covn.pd n=7,16 | chg from baseline-end of monotherapy pd n=7,18 |
|---|
| ESL 1600 mg | -6.6 | -4.1 |
,| ESL1200 mg | -3.9 | -6.1 |
Change in Total Score in Montgomery-Asberg Depression Rating Scale (MADRS),From Baseline .
The total score of MADRS is defined as the sum of all individual item scores. From 0-60, high score indicates more severe (NCT01091662)
Timeframe: Week 0 to Week 18,baseline day 0; end of AED taper/conversion period; end of week 8; end of monotherapy period; end of week 18
| Intervention | units on a scale (Mean) |
|---|
| chg from baseline-end of AED taper/covn.pd n=48,88 | chg from baseline-end of monotherapy pd n=54,98 |
|---|
| ESL 1600 mg | -1.8 | -1.6 |
,| ESL1200 mg | -1.2 | 0.0 |
Completion Rate (% of Subjects Completing the 18 Weeks of Double-blind Treatment).
Subjects completing the study were determined as subjects who completed the 18 weeks of double-blind treatment. (NCT01091662)
Timeframe: 18 weeks
| Intervention | percentage of participants (Number) |
|---|
| ESL1200 mg | 75.9 |
| ESL 1600 mg | 80.0 |
Completion Rate During the 10 Weeks of Monotherapy (% of Subjects Entering the Monotherapy Period Who Complete).
Monotherapy completion rate was defined as the proportion (%) of subjects entering the monotherapy period who completed the 10 weeks of monotherapy treatment. (NCT01091662)
Timeframe: Week 8 through 18
| Intervention | percentage of participants (Number) |
|---|
| ESL1200 mg | 85.4 |
| ESL 1600 mg | 90.9 |
Change From Baseline to Endpoint in Mean Pain
"The efficacy analysis was restricted to the primary efficacy variable in the analysis population. The intended treatment period, starting on the day of the randomization and ending at the efficacy cut-off date (October 31, 2011), was the basis for the analysis.~The primary efficacy variable was the difference between the mean values of 7 daily pain scores preceding the efficacy cut-off date (endpoint mean pain score), and before randomization (baseline mean pain score), respectively. The daily pain scores were based on the morning response to the 11-point Numeric Rating Pain Scale (NRPS) question relating to average pain intensity over the last 24 hours. The NPRS is an 11-point scale from 0-10 [0 = no pain; 10 = the most intense pain imaginable]" (NCT01124097)
Timeframe: baseline to endpoint
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Esl 1600 mg QD | -1.19 |
| Esl 1200 mg QD | -1.34 |
| Esl 800 mg Once Daily (QD) | -0.94 |
| Placebo | -0.77 |
Change From Baseline to Endpoint in Mean Pain
"Study was prematurely halted. The efficacy analysis was restricted to the primary efficacy variable in the interim analysis population. The intended treatment period, starting on the day of the randomization and ending at the efficacy cut-off date (31st October 2011), was the basis for the efficacy analysis; patients with less than 20 days of study medication were excluded from the analysis, except those with early discontinuation. Primary efficacy variable was the difference between the mean values of 7 daily pain scores preceding the efficacy cut-off date (endpoint mean pain score), and before randomization (baseline mean pain score), respectively. The daily pain scores were based on the morning response to the 11-point Numeric Rating Pain Scale (NRPS) question relating to average pain intensity over the last 24 hours. The NPRS is an 11-point scale from 0-10 [0 = no pain; 10 = the most intense pain imaginable]" (NCT01129960)
Timeframe: baseline up to endpoint 15 weeks (3-week titration phase and 12-week treatment maintenance phase)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Esl 1600 mg | -1.56 |
| Esl 1200 mg | -0.90 |
| Esl 800 mg | -1.73 |
| Placebo | -1.13 |
Change From Baseline in Standardized Seizure Frequency
Absolute and relative changes from baseline of seizure frequency standardised to a frequency per 4 weeks. (NCT01422720)
Timeframe: 8-week Baseline Period and 26-week Treatment Period
| Intervention | seizures/4 weeks (Mean) |
|---|
| FAS - Baseline Period | 4.8 |
| FAS - Treatment Period | 3.6 |
| PPS - Baseline Period | 4.0 |
| PPS- Treatment Period | 3.1 |
Number of Subjects With Reported Adverse Events (AE)
"An AE was defined as Treatment-Emergent Adverse Event (TEAE), if first onset or worsening was after the first intake of investigational medicinal product (IMP) and not more than 14 days after the last administration of IMP.~TEAE assessment:~patients who died~patients who died due to Treatment-emergent adverse event (TEAE)~patients with at least one Serious Adverse Event (SAE)~patients with at least one Treatment-emergent Serious Adverse Event (TESAE)~patients prematurely terminated due to TEAE~patients with at least one TEAE~patients with at least one related TEAE~patients with at least one severe TEAE~patients without any TEAE" (NCT01422720)
Timeframe: throughout the study
| Intervention | participants (Number) |
|---|
| patients who died | patients who died due to TEAE | patients with at least one SAE | patients with at least one TESAE | patients prematurely terminated due to TEAE | patients with at least one TEAE | patients with at least one related TEAE | patients without any TEAE | patients with at least one severe TEAE |
|---|
| Esl 800 mg | 3 | 3 | 11 | 10 | 18 | 47 | 31 | 25 | 12 |
Change From Baseline in Power of Attention Score to the End of the Double Blind (DB) Period
Power of Attention was defined as the sum of the reaction time measures from the attentional tasks (simple [dominant hand only] reaction time, choice reaction time and digit vigilance speed) in order to assess information processing speed and attention/psychomotor speed.Change from baseline to the end of the double-blind period in Power of Attention will be compared between the treatment groups using an ANCOVA. Non-inferiority of ESL vs Placebo will be assessed by comparing the 95% CI's upper bound of the difference of Least Squares Mean (LSmeans) between treatment groups (ESL-placebo) with 121 ms. If the upper bound is greater than 121 ms then the null hypothesis that the change from baseline in the Power of Attention score in ESL group is at least 121 ms inferior than the placebo group will be rejected. Single Values were calculated the average of post treatment visits (visits 5 and 7or EDV) minus average of baseline visits (visits 1 and 2) (NCT01527513)
Timeframe: Visit 1 (-4 weeks for training), Visit 2 (Day 1), Visit 5 (6 weeks), Visit 7 (12 weeks) or at early discontinuation visit (EDV)
| Intervention | Milli seconds (ms) (Mean) |
|---|
| Placebo | 111.085 |
| Esl (BIA 2-093) | 59.122 |
Change From Baseline in Seizure Frequency During the One-year Open-Label (OL)
Overall Change from Baseline in Seizure Frequency per week for the One-Year Open-Label Period (NCT01527513)
Timeframe: Weeks 1 to ≥ 41 weeks
| Intervention | Seizure per week (Mean) |
|---|
| Esl PART II | -3.03 |
Change From Baseline in Standardized Seizure Frequency - Part I
(NCT01527513)
Timeframe: Baseline; Titration Period (4 Weeks: V2-V3-V4)
| Intervention | Seizures per week (Mean) |
|---|
| Placebo | -9.13 |
| Esl (BIA 2-093) | -31.03 |
Total of Subjects Reporting at Least One Adverse Event
Monitoring of Adverse Events throughout the study: Safety was evaluated from the number of reported adverse events (AEs) by patient (NCT01678976)
Timeframe: 4 weeks
| Intervention | subjects reporting at least 1 AE (Number) |
|---|
| All treatment-emergent AEs | Possibly related to treatment AEs |
|---|
| BIA 2-093 | 6 | 5 |
,| Oxcarbazepine | 6 | 4 |
Maximum Drug Concentration (Cmax)
Maximum observed plasma concentration (Cmax) was acessed for BIA 2-093 metabolites (BIA 2-194; BIA 2-195) and Oxcarbazepine. (NCT01678976)
Timeframe: at pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-194) | Cmax (BIA 2-195) | Cmax (Oxcarbazepine) |
|---|
| BIA 2-093 900 mg od | 15753 | 428 | 140 |
,| Oxcarbazepine 900 mg od | 5978 | 1708 | 1268 |
Area Under the Plasma Concentration Versus Time Curve (AUC)
Area under the plasma concentration versus time curve (AUC) to last measurable time point (AUC0-t) was acessed for BIA 2-093 metabolites (BIA 2-194; BIA 2-195) and Oxcarbazepine. (NCT01678976)
Timeframe: at pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose
| Intervention | ng*h/mL (Mean) |
|---|
| AUC0-t (BIA 2-194) | AUC0-t (BIA 2-195) | AUC0-t (Oxcarbazepine) |
|---|
| BIA 2-093 900 mg od | 299065 | 13877 | 1821 |
,| Oxcarbazepine 900 mg od | 214433 | 49124 | 6549 |
AUC - Area Under the Plasma Concentration Versus Time Curve
"AUC - Area Under the Plasma Concentration Versus Time Curve for BIA 2-093 metabolites:~BIA 2-194 BIA 2-195 Oxcarbazepine" (NCT01679002)
Timeframe: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose
| Intervention | ng*h/mL (Mean) |
|---|
| AUC0-t (BIA 2-194) | AUC0-t (BIA 2-195) | AUC0-t (Oxcarbazepine) |
|---|
| BIA 2-093 450 mg Bid | 283014 | 19091 | 2699 |
,| BIA 2-093 900 mg od | 381601 | 20164 | 3238 |
,| Oxcarbazepine 450 mg Bid | 268376 | 48841 | 5196 |
Number of of Subjects Reporting at Least One Adverse Event
Number of of subjects reporting at least one adverse event. (NCT01679002)
Timeframe: 8 weeks
| Intervention | Number of of subjects reporting at least (Number) |
|---|
| BIA 2-093 900 mg od | 9 |
| BIA 2-093 450 mg Bid | 10 |
| Oxcarbazepine 450 mg Bid | 11 |
Cmax - Maximum Observed Plasma Drug Concentration
"Cmax - maximum observed plasma drug concentration for BIA 2-093 metabolites:~BIA 2-194 BIA 2-195 Oxcarbazepine" (NCT01679002)
Timeframe: pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 h post-dose
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-194) | Cmax (BIA 2-195) | Cmax (Oxcarbazepine) |
|---|
| BIA 2-093 450 mg Bid | 16667 | 702 | 182 |
,| BIA 2-093 900 mg od | 22210 | 685 | 208 |
,| Oxcarbazepine 450 mg Bid | 12195 | 2481 | 1080 |
Absolute Change From Baseline in the Frequency of Migraine Attacks
The primary efficacy variable was the absolute change from baseline in the frequency of migraine attacks standardised to 4 weeks in the Maintenance Period, as recorded in the subject diary. If there were less than 24 h between the end of 1 migraine event and the start of the next event, these 2 events were considered to belong to 1 migraine attack. There had to be a minimum of 24 h of freedom from headache, pain, and symptoms of migraine between attacks recorded in the subject diary to be considered as more than 1 attack of migraine for statistical analysis. (NCT01820559)
Timeframe: 4 weeks
| Intervention | number of migraine attacks/participant (Least Squares Mean) |
|---|
| Placebo | -0.8 |
| ESL 800 mg | -1.0 |
| ESL 1200 mg | -1.0 |
Absolute Change From Baseline to Endpoint in Mean Pain
The primary efficacy variable was the absolute change from baseline to endpoint in mean pain. Pain intensity was assessed on an 11-point (0-10) Numeric pain rating scale (NPRS), where 0 = no pain and 10 = worst possible pain and was recorded in a subject's diary. The subject was instructed to complete the assessment daily on awakening.Primary analyses were conducted on the full analysis set (FAS) which consisted of all randomised subjects who received at least 1 dose of study medication and with at least 1 post-randomisation rating of 24-h-average pain. The primary efficacy variable was the absolute change from baseline to endpoint in mean pain recorded in a subject's diary upon awakening each morning. An ANCOVA on the FAS revealed no statistically significant differences between the 3 ESL groups and the placebo group after 13 weeks of treatment. (NCT01820585)
Timeframe: Baseline and 13 Weeks
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Placebo | -1.0 |
| ESL 400 mg | -0.8 |
| ESL 800 mg | -1.2 |
| ESL 1200 mg | -0.8 |
Change in the Young Mania Rating Scale (YMRS) Total Score at the End of the 3-week Treatment Period, in Relation to the Baseline.
The YMRS is used to assess disease severity in patients who have been previously diagnosed with mania and it has proven psychometric properties through 11 item multiple-choice diagnostic questionnaire and the total score is determined from the summation of each 11 individual scores (and can range from 0 - 60) based on the patient's subjective feedback of his clinical condition over the previous 48 hours. A higher score indicates a worse rating for symptoms related to mania. At every visit throughout the study, investigators administered the YMRS. The results of the primary analysis of efficacy were calculated using Analysis of covariance (ANCOVA) with Last Observation Carried Forward (LOCF). Primary variable is presented through ANCOVA results for absolute change in YMRS total score from baseline (V2) to end of treatment (V7). A responder has at least 50% improvement (reduction) in the YMRS total score or has a total score of less than 12 points at the end of treatment period. (NCT01822678)
Timeframe: baseline and 3-week
| Intervention | units on a scale (Least Squares Mean) |
|---|
| BIA 2-093 - 2400 mg (Maximum Dose) | -14.2 |
| BIA 2-093 - 1800 mg (Maximum Dose) | -12.5 |
| Placebo | -10.3 |
Change in Young Mania Rating Scale (YMRS) Total Score From Baseline Until the End of the 3-week Treatment Period
The YMRS is used to assess disease severity in patients who have been previously diagnosed with mania and it has proven psychometric properties through 11 item multiple-choice diagnostic questionnaire and the total score is determined from the summation of each 11 individual scores (and can range from 0 - 60) based on the patient's subjective feedback of his clinical condition over the previous 48 hours. A higher score indicates a worse rating for symptoms related to mania. At every visit throughout the study, investigators administered the YMRS. The results of the primary analysis of efficacy were calculated using Analysis of covariance (ANCOVA) with Last Observation Carried Forward (LOCF). Primary variable is presented through ANCOVA results for absolute change in YMRS total score from baseline (V2) to end of treatment (V7). A responder has at least 50% improvement (reduction) in the YMRS total score or has a total score of less than 12 points at the end of treatment period. (NCT01824602)
Timeframe: baseline and 3-week
| Intervention | units on a scale (Mean) |
|---|
| Placebo | -17.7 |
| ESL 600 mg | -16.9 |
| ESL 1200 mg | -16.7 |
| ESL 1800 mg | -11.3 |
Proportion of Patients Who Showed no Worsening According to the Clinical Global Impression - Bipolar Version (CGI-BP) Scale (Intent-to-Treat Population)
The CGI-BP scale is a modification of the CGI scale, which provides a means of assessing severity and treatment-related improvement in manic and depressive domains reflecting clinically relevant degrees of change. The concept of improvement refers to the clinical distance between the individual's current condition and that prior to the start of treatment. The scale for 'severity of illness' measures mania, depression and overall illness on a 7 point scale from 1 ('normal, not ill') to 7 ('very severely ill'). The scale for 'change from preceding phase' and 'change from worst phase' measures mania, depression, and overall illness on an 8-point scale from 1 (very much improved) to 8 ('not applicable'). If the patient, in 'change from preceding phase', at any visit during the double-blind, has a score of 5, 6, or 7 in any of 3 categories (mania, depression, or overall bipolar illness), then the illness will be considered to have worsened. (NCT01825837)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| BIA 2-093 300 mg | 26 |
| BIA 2-093 900 mg | 14 |
| BIA 2-093 1800 mg | 16 |
Number of Adverse Events Reported
Safety was evaluated through the recording and monitoring of adverse events (NCT01879332)
Timeframe: 2 days
| Intervention | Number of adverse events reported (Number) |
|---|
| Nervous system AE | Gastrointestinal AE | General and Administration Site Conditions AE | Eye AE | Skin and Subcutaneous Tissue AE |
|---|
| BIA 2-093 3000 mg Once Daily | 6 | 5 | 4 | 1 | 1 |
,| BIA 2-093 3600 mg Once Daily | 6 | 4 | 1 | 1 | 0 |
,| Placebo | 1 | 1 | 0 | 0 | 0 |
Number of Adverse Events Reported
investigate the tolerability of two single- and multiple-dose regimens of BIA 2-093 (1800 mg and 2400 mg)considering the Number of adverse events reported by patient (NCT01879345)
Timeframe: 3 weeks
| Intervention | Number of adverse events reported (Number) |
|---|
| BIA 2-093 - 1800 mg (Group 1) | 10 |
| BIA 2-093 - 2400 mg (Group 2) | 7 |
| Placebo | 7 |
AUC0-τ
Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 (NCT01879345)
Timeframe: Day 1 and Day 7
| Intervention | ng.h/mL (Mean) |
|---|
| AUC0-τ (BIA 2-005) single dose | AUC0-τ (BIA 2-005) multiple dose | AUC0-τ (oxcarbazepine) single dose | AUC0-τ (oxcarbazepine) multiple dose |
|---|
| BIA 2-093 - 1800 mg (Group 1) | 507563 | 740299 | 3589 | 6958 |
,| BIA 2-093 - 2400 mg (Group 2) | 445596 | 905860 | 4547 | 9956 |
Cmax - Maximum Observed Plasma Drug Concentration
"Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093~Oxcarbazepine is a BIA 2-093 metabolite" (NCT01879345)
Timeframe: Day 1 and Day 7
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-005) single dose | Cmax (BIA 2-005) multiple dose | Cmax (oxcarbazepine) single dose | Cmax (oxcarbazepine) multiple dose |
|---|
| BIA 2-093 - 1800 mg (Group 1) | 34569 | 47665 | 241 | 361 |
,| BIA 2-093 - 2400 mg (Group 2) | 35926 | 56506 | 508 | 734 |
Tmax - the Time of Occurrence of Cmax
Single dose: pharmacokinetic parameters following an oral single-dose of BIA 2-093 Multiple dose: pharmacokinetic parameters following the last dose of an oral 7- day once-daily regimen of BIA 2-093 (NCT01879345)
Timeframe: Day 1 and Day 7
| Intervention | hours (Mean) |
|---|
| tmax (BIA 2-005) single dose | tmax (BIA 2-005) multiple dose | tmax (oxcarbazepine) single dose | tmax (oxcarbazepine) multiple dose |
|---|
| BIA 2-093 - 1800 mg (Group 1) | 3.8 | 2.1 | 4.67 | 3.83 |
,| BIA 2-093 - 2400 mg (Group 2) | 3.3 | 3.6 | 4.00 | 3.67 |
Assessment of Taste Preference
Subject preference for 3 flavours of the ESL oral suspension was assessed based on a measured score using a 0-10 cm (minimum and maximum measured values) Visual Analogue Scale (VAS). Higher values represent the stronger preference. (NCT02021461)
Timeframe: single Study Day
| Intervention | units on a scale (0-10 cm VAS) (Mean) |
|---|
| ESL Banana Taste | 5.8 |
| ESL Grape Taste | 5.8 |
| ESL Tutti-Frutti Taste | 7.1 |
Time of Occurrence of Cmax (Tmax).
(NCT02170064)
Timeframe: pre-dose, and ½, 1½, 3, 4½, 6 and 12 hours post-dose
| Intervention | hours (Mean) |
|---|
| Dosage regimen 5 mg/kg/day | Dosage regimen 15 mg/kg/day | Dosage regimen 30 mg/kg/day |
|---|
| Group 1 (2-6 Yrs) | 1 | 2 | 1 |
,| Group 2 (7-11 Yrs) | 2 | 3 | 3 |
,| Group 3 (12-17 Yrs) | 2 | 2 | 3 |
Maximum Observed Plasma Drug Concentration (Cmax) Post-dose
(NCT02170064)
Timeframe: pre-dose, and ½, 1½, 3, 4½, 6 and 12 hours post-dose
| Intervention | ng/mL (Mean) |
|---|
| Dosage regimen 5 mg/kg/day | Dosage regimen 15 mg/kg/day | Dosage regimen 30 mg/kg/day |
|---|
| Group 1 (2-6 Yrs) | 6921 | 16183 | 29935 |
,| Group 2 (7-11 Yrs) | 4820 | 16395 | 26890 |
,| Group 3 (12-17 Yrs) | 6382 | 17194 | 32400 |
Percentage Change in Seizure Frequency During Each 4-week Treatment Period Compared to the Baseline Phase
"The efficacy variables were the percentage change in seizure frequency during each 4-week treatment period compared to the baseline phase.~Seizures were recorded in the patient's diary during the baseline phase and during the following 4-week treatment periods.~Seizure frequency for each patient was standardised to a frequency per 28 days period (i.e., mean daily frequency multiplied by 28). Changes in seizure frequency were analysed for each age group separately." (NCT02170064)
Timeframe: Baseline, end of 5 mg/kg/day treatment period (4 weeks), 15 mg/kg/day treatment period (4 weeks) and 30 mg/kg/day treatment period (4 weeks).
| Intervention | percent change (Median) |
|---|
| 5Dosage regimen 5 mg/kg/day | Dosage regimen 15 mg/kg/day | Dosage regimen 30 mg/kg/day |
|---|
| Group 1 (2-6 Yrs) | -28.2 | -24.8 | -40.6 |
,| Group 2 (7-11 Yrs) | -11.7 | 5.0 | 12.2 |
,| Group 3 (12-17 Yrs) | -17.1 | -31.7 | -43.1 |
"The Percentage of Participants With a 50% or Greater Reduction in Seizure Frequency (Further Referred to as Responders) in a Treatment Period Compared to the Baseline Period"
(NCT02170077)
Timeframe: baseline, week 12
| Intervention | percentage of responders (Number) |
|---|
| ODG - Once Daily Group | 54 |
| TDG - Twice Daily Group | 41 |
| PLG - Placebo Group | 28 |
Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC0-oo)
Area under the plasma concentration versus time curve from time zero to infinity (AUC0-oo) of BIA 2-093 (NCT02170649)
Timeframe: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose
| Intervention | ng.h/mL (Mean) |
|---|
| Fasting | Fed |
|---|
| Single Group | 243589 | 242459 |
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification (AUC0-t)
Area under the plasma concentration versus time curve from time zero to the last sampling time at which concentrations were at or above the limit of quantification (AUC0-t) of BIA 2-093 (NCT02170649)
Timeframe: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose
| Intervention | ng.h/mL (Mean) |
|---|
| Fasting | Fed |
|---|
| Single Group | 243155 | 229350 |
Maximum Observed Plasma Concentration (Cmax)
Maximum observed plasma concentration of BIA 2-093 (NCT02170649)
Timeframe: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose
| Intervention | ng/mL (Mean) |
|---|
| Fasting | Fed |
|---|
| Single Group | 11302 | 12799 |
Time of Occurrence of Cmax (Tmax)
Time of occurrence of Cmax of BIA 2-093 (NCT02170649)
Timeframe: pre-dose, ½, 1, 1½, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72 and 96 hours post-dose
| Intervention | hours (Median) |
|---|
| Fasting | Fed |
|---|
| Single Group | 3.5 | 4.0 |
Total Number of Adverse Events
An adverse event was defined as any undesirable event occurring to a subject during the study, whether or not related to the investigational product (NCT02171195)
Timeframe: up to 20 weeks
| Intervention | Number of Adverse Events (Number) |
|---|
| All Adverse Events | AE Considered Not Related to Treatment | AE Considered Possibly Related to Treatment | AE of Mild Severity | AE of Moderate Severity |
|---|
| Group 1 20 mg | 7 | 2 | 5 | 5 | 2 |
,| Group 2 50 mg | 3 | 0 | 3 | 3 | 0 |
,| Group 3 100 mg | 7 | 0 | 7 | 6 | 1 |
,| Group 4 200 mg | 2 | 0 | 2 | 2 | 0 |
,| Group 5 400 mg | 1 | 0 | 1 | 1 | 0 |
,| Group 6 600 mg | 1 | 0 | 1 | 1 | 0 |
,| Group 7 900 mg | 2 | 0 | 2 | 2 | 0 |
,| Group 8 1200 mg | 7 | 4 | 3 | 7 | 0 |
,| Placebo | 7 | 0 | 7 | 7 | 0 |
Total Number of Adverse Events
Total Number of Adverse Events. (NCT02171234)
Timeframe: up to 20 weeks
| Intervention | Total Number of AE (Number) |
|---|
| All Adverse Events | AE Considered Not Related to Treatment | AE Considered Possibly Related to Treatment | Adverse Events of Mild Severity | Adverse Events of Moderate Severity |
|---|
| Group 1 - BIA 2-093 200 mg b.i.d. | 9 | 3 | 6 | 9 | 0 |
,| Group 2 - BIA 2-093 400 mg o.d. | 15 | 2 | 13 | 15 | 0 |
,| Group 3 - BIA 2-093 800 mg o.d. | 5 | 0 | 5 | 4 | 1 |
,| Group 4 - BIA 2-093 1200 mg o.d. | 12 | 0 | 12 | 12 | 0 |
,| Placebo | 14 | 1 | 13 | 14 | 0 |
Cmax
Cmax - Maximum observed plasma concentration (NCT02171234)
Timeframe: Day 1 and Day 8
| Intervention | ng/ml (Mean) |
|---|
| Cmax Day 1 | Cmax Day 8 |
|---|
| Group 1 - BIA 2-093 200 mg b.i.d. | 3086 | 6683 |
,| Group 2 - BIA 2-093 400 mg o.d. | 7827 | 8824 |
,| Group 3 - BIA 2-093 800 mg o.d. | 11074 | 18675 |
,| Group 4 - BIA 2-093 1200 mg o.d. | 16071 | 25457 |
AUC0-τ
"AUC0-τ - Area under the plasma concentration time curve to last measurable time point~Day 1 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, hours post final dose Day 8 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, 24, 36, 48 and 72 hours post final dose" (NCT02171234)
Timeframe: Day 1 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, hours post final dose Day 8 - pre-dose, 30, 60, 90, 120, 180 minutes, 4, 6, 7, 8, 12, 24, 36, 48 and 72 hours post final dose
| Intervention | ng.h/ml (Mean) |
|---|
| AUC0-τ Day 1 | AUC0-τ Day 8 |
|---|
| Group 1 - BIA 2-093 200 mg b.i.d. | 22163 | 63140 |
,| Group 2 - BIA 2-093 400 mg o.d. | 96262 | 126308 |
,| Group 3 - BIA 2-093 800 mg o.d. | 159492 | 268384 |
,| Group 4 - BIA 2-093 1200 mg o.d. | 250426 | 423003 |
Cmax - Maximum Steady-state Plasma Concentration
Cmax - Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin (NCT02172742)
Timeframe: Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-005) | Cmax (Digoxin) (Digoxin+Placebo) | Cmax (Digoxin) (Digoxin+BIA 2-093) |
|---|
| BIA 2-093 + Placebo | 27571 | 2,350 | 1,909 |
AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h
Steady-state Area Under the Plasma Concentration-time Profile Over 24 h of BIA 2-005 (BIA 2-093 metabolite) and Digoxin (NCT02172742)
Timeframe: Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose
| Intervention | ng*h/mL (Mean) |
|---|
| AUCτ (BIA 2-005) | AUCτ (Digoxin) (Digoxin+Placebo) | AUCτ (Digoxin) (Digoxin+BIA 2-093) |
|---|
| BIA 2-093 + Placebo | 370297 | 17607 | 16595 |
Tmax - Time of Occurrence of Cmax at Steady-state
Time of Occurrence of Cmax Maximum steady-state plasma concentration of BIA 2-005 (BIA 2-093 metabolite) and Digoxin (NCT02172742)
Timeframe: Day 6 and Day 7: pre-dose; Day 8: pre-dose, ½, 1, 2, 3, 4, 6, 8, 12, 18, and 24 hours post-dose
| Intervention | hours (Median) |
|---|
| tmax (BIA 2-005) | tmax (Digoxin) (Digoxin+placebo) | tmax (Digoxin) (Digoxin+BIA 2-093) |
|---|
| BIA 2-093 + Placebo | 2 | 1 | 1 |
Maximum Drug Concentration (Cmax)
"Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose.~Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels).~Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose.~BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093" (NCT02172755)
Timeframe: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p
| Intervention | ng/mL (Mean) |
|---|
| Single dose (BIA 2-194) | Multiple dose (BIA 2-194) | Single dose (BIA 2-195) | Multiple dose (BIA 2-195) | Single dose (oxcarbazepine) | Multiple dose (oxcarbazepine) |
|---|
| Elderly Subjects | 9469 | 15067 | 209 | 531 | 76.3 | 135 |
,| Young Subjects | 9867 | 17309 | 192 | 461 | 77.3 | 150 |
Tmax - Time of Maximum Observed Concentration
"Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose.~Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels).~Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose.~BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093" (NCT02172755)
Timeframe: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p
| Intervention | hours (Mean) |
|---|
| Single dose (BIA 2-194) | Multiple dose (BIA 2-194) | Single dose (BIA 2-195) | Multiple dose (BIA 2-195) | Single dose (oxcarbazepine) | Multiple dose (oxcarbazepine) |
|---|
| Elderly Subjects | 2.96 | 2.04 | 13.6 | 7.29 | 5.41 | 2.67 |
,| Young Subjects | 3.00 | 2.04 | 11.3 | 7.58 | 5.41 | 2.67 |
AUC0-t - Area Under the Plasma Concentration-time Curve to Last Measurable Time Point
"Single-dose period: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose.~Multiple-dose period: from Day 5 to Day 11 inclusive, early in the morning, before the daily dose (for trough levels).~Day 12: pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-last dose.~BIA 2-194, BIA 2-195, and oxcarbazepine are metabolites of BIA 2-093" (NCT02172755)
Timeframe: Day 1 at pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, and 96 hours post-dose From Day 5 to Day 11 inclusive, before the daily dose (for trough levels). On Day 12, pre-dose, and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours p
| Intervention | ng.h/mL (Mean) |
|---|
| Single dose (BIA 2-194) | Multiple dose (BIA 2-194) | Single dose (BIA 2-195) | Multiple dose (BIA 2-195) | Single dose (oxcarbazepine) | Multiple dose (oxcarbazepine) |
|---|
| Elderly Subjects | 190521 | 288364 | 5738 | 15911 | 1014 | 1508 |
,| Young Subjects | 174713 | 290630 | 3361 | 12782 | 577 | 1490 |
Tmax - the Time of Occurrence of Cmax
Tmax - the Time of Occurrence of maximum plasma concentration of BIA 2-093 metabolite: BIA 2-005 (NCT02279667)
Timeframe: Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
| Intervention | hours (Median) |
|---|
| BIA 2-093 16 mL Oral Suspension 50 mg/mL | 2 |
| BIA 2-093 - Four 200 mg Tablets | 3 |
| BIA 2-093 One 800 mg Tablet | 3 |
Cmax - the Maximum Plasma Concentration
Cmax - the maximum plasma concentration of BIA 2-093 metabolite: BIA 2-005 (NCT02279667)
Timeframe: Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
| Intervention | ng/mL (Mean) |
|---|
| BIA 2-093 16 mL Oral Suspension 50 mg/mL | 18048 |
| BIA 2-093 - Four 200 mg Tablets | 16007 |
| BIA 2-093 One 800 mg Tablet | 17042 |
AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time
AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time of BIA 2-093 metabolite: BIA 2-005 (NCT02279667)
Timeframe: Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
| Intervention | ng*h/mL (Mean) |
|---|
| BIA 2-093 16 mL Oral Suspension 50 mg/mL | 323277 |
| BIA 2-093 - Four 200 mg Tablets | 302026 |
| BIA 2-093 One 800 mg Tablet | 299016 |
AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity
AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity of BIA 2-093 metabolite: BIA 2-005 (NCT02279667)
Timeframe: Blood samples for PK assays: pre-dose, 30, 60 and 90 minutes, and 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose
| Intervention | ng*h/mL (Mean) |
|---|
| BIA 2-093 16 mL Oral Suspension 50 mg/mL | 325732 |
| BIA 2-093 - Four 200 mg Tablets | 304219 |
| BIA 2-093 One 800 mg Tablet | 301065 |
Cmax - Peak Plasma Concentration
BIA 2-194; BIA 2-195; Oxcarbazepine are BIA 2-093 metabolites (NCT02281422)
Timeframe: pre-dose and 1, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 7, 9, 12, 24, 48, 72 and 96 hours post-dose.
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-194) | Cmax (BIA 2-195) | Cmax (Oxcarbazepine) |
|---|
| Group 1 Normal Renal Function | 14286.790 | 211.076 | 138.339 |
,| Group 2 Mild Renal Impairment | 18677.265 | 348.843 | 172.293 |
,| Group 3 Moderate Renal Impairment | 15055.632 | 410.828 | 157.629 |
,| Group 4 Severe Renal Impairment | 14974.79 | 465.928 | 157.955 |
,| Group 5 End Stage Renal Disease | 14510.197 | 359.798 | 208.473 |
AUC(0-12h) - AUC From Time Zero to 12h
"BIA 2-194; BIA 2-195; Oxcarbazepine are BIA 2-093 metabolites~AUC - area under the plasma concentration versus time curve" (NCT02281422)
Timeframe: pre-dose and 1, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 7, 9, 12, 24, 48, 72 and 96 hours post-dose.
| Intervention | ng*h/mL (Mean) |
|---|
| AUC(0-12h) (BIA 2-194) | AUC(0-12h) (BIA 2-195) | AUC(0-12h) (Oxcarbazepine) |
|---|
| Group 1 Normal Renal Function | 105275.733 | 1522.370 | 1218.276 |
,| Group 2 Mild Renal Impairment | 150945.034 | 2435.245 | 1388.146 |
,| Group 3 Moderate Renal Impairment | 138473.115 | 2025.731 | 1460.113 |
,| Group 4 Severe Renal Impairment | 138262.814 | 2157.860 | 1496.463 |
,| Group 5 End Stage Renal Disease | 134757.936 | 2690.584 | 1832.298 |
Tmax (hr) - Time at Which Cmax Occurred
"BIA 2-194; BIA 2-195; Oxcarbazepine are BIA 2-093 metabolites~Cmax - maximum observed plasma drug concentration" (NCT02281422)
Timeframe: pre-dose and 1, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 5, 7, 9, 12, 24, 48, 72 and 96 hours post-dose.
| Intervention | hours (Mean) |
|---|
| Tmax (BIA 2-194) | Tmax (BIA 2-195) | Tmax (Oxcarbazepine) |
|---|
| Group 1 Normal Renal Function | 1.121 | 22.008 | 2.396 |
,| Group 2 Mild Renal Impairment | 1.327 | 20.185 | 2.581 |
,| Group 3 Moderate Renal Impairment | 2.609 | 26.172 | 3.970 |
,| Group 4 Severe Renal Impairment | 2.680 | 33.947 | 4.787 |
,| Group 5 End Stage Renal Disease | 1.633 | 10.773 | 4.260 |
AUC0-t
AUC0-t (ng.h/mL) following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference) (NCT02281448)
Timeframe: pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.
| Intervention | pg.h/mL (Mean) |
|---|
| AUC0-t (ethinyloestradiol) Test | AUC0-t (ethinyloestradiol) Reference | AUC0-t (Levonorgestrel) Test | AUC0-t (Levonorgestrel) Reference |
|---|
| Overall Population | 347 | 595 | 24000 | 33600 |
Cmax
Cmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference) (NCT02281448)
Timeframe: pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.
| Intervention | pg/mL (Mean) |
|---|
| Cmax (ethinyloestradiol) Test | Cmax (ethinyloestradiol) Reference | Cmax (Levonorgestrel) Test | Cmax (Levonorgestrel) Reference |
|---|
| Overall Population | 53.4 | 66.1 | 3220 | 3720 |
Cmax - Maximum Observed Plasma BIA 2-194 Concentration
Cmax - Maximum observed plasma BIA 2-194 concentration on days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily. (NCT02281448)
Timeframe: Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 during a 15-day oral regimen of BIA 2-093 1200 mg once-daily.
| Intervention | ng/mL (Mean) |
|---|
| Day 1 | Day 2 | Day 4 | Day 6 | Day 8 | Day 10 | Day 12 | Day 14 | Day 15 |
|---|
| Cmax (BIA 2-194) | 0.00 | 8443 | 10691 | 10961 | 10175 | 10332 | 10821 | 10670 | 9978 |
Tmax
Tmax following administration of a single-dose of Microginon® concomitantly with the 14th dose of a 15-day oral regimen of BIA 2-093 1200 mg once-daily (Test) and following administration of a single-dose of Microginon® administered alone (Reference) (NCT02281448)
Timeframe: pre-dose, on Days 1, 2, 4, 6, 8, 10, 12, 14 and 15 of the BIA 2-093 + OC period.
| Intervention | h (Mean) |
|---|
| tmax (ethinyloestradiol) Test | tmax (ethinyloestradiol) Reference | tmax (Levonorgestrel) Test | tmax (Levonorgestrel) Reference |
|---|
| Overall Population | 1.67 | 1.52 | 1.28 | 1.21 |
Cmax - Peak Plasma Concentration
Day 1 - Cmax Peak plasma concentration (NCT02281526)
Timeframe: pre-dose and 1, 2, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 7, 9, 12 and 24 hours post-dose.
| Intervention | ng/mL (Mean) |
|---|
| Cmax BIA 2-093 | Cmax BIA 2-194 | Cmax 2-195 Glucoronide | Cmax Oxcarbazepine | Cmax BIA 2-093 Glucoronide | Cmax BIA 2-194 Glucoronide |
|---|
| Subjects - Healthy Controls | 99.500 | 18180.000 | 16.667 | 121.000 | 5.000 | 1381.125 |
,| Subjects With Moderate Hepatic Impairment | 477.500 | 16392.778 | 16.875 | 100.111 | 9.000 | 1067.000 |
Area Under the Plasma Concentration Versus Time Curve, AUC(0-tlast).
"Day 1 - Area under the plasma concentration versus time curve, AUC(0-tlast).~BIA 2-194, 2-195 Glucoronide, Oxcarbazepine, BIA 2-093 Glucoronide, 2-194 Glucoronide are BIA 2-093 metabolites." (NCT02281526)
Timeframe: pre-dose and 1, 2, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 7, 9, 12 and 24 hours post-dose.
| Intervention | h·ng/mL (Mean) |
|---|
| AUC(0-tlast) BIA 2-093 | AUC(0-tlast) BIA 2-194 | AUC(0-tlast) 2-195 Glucoronide | AUC(0-tlast) Oxcarbazepine | AUC(0-tlast) BIA 2-093 Glucoronide | AUC(0-tlast) BIA 2-194 Glucoronide |
|---|
| Subjects - Healthy Controls | 49.750 | 234750.429 | 157.738 | 1899.092 | 2.500 | 11642.372 |
,| Subjects With Moderate Hepatic Impairment | 954.891 | 240188.369 | 50.603 | 1489.530 | 6.875 | 8634.780 |
Cmax - the Maximum Plasma Concentration
(NCT02281591)
Timeframe: Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-194) | Cmax (BIA 2-195) | Cmax (Oxcarbazepine) |
|---|
| Eslicarbazepine Acetate | 15809 | 222 | 136 |
,| R-licarbazepine | 437 | 6941 | 101 |
,| S-licarbazepine | 10364 | 132 | 92.8 |
,| S-licarbazepine R-licarbazepine | 10496 | 8099 | 261 |
Tmax - the Time of Occurrence of Cmax
(NCT02281591)
Timeframe: Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.
| Intervention | hours (Mean) |
|---|
| tmax (BIA 2-194) | tmax (BIA 2-195) | tmax (Oxcarbazepine) |
|---|
| Eslicarbazepine Acetate | 1.99 | 18.6 | 3.59 |
,| R-licarbazepine | 10.7 | 1.22 | 1.21 |
,| S-licarbazepine | 0.965 | 11.7 | 1.36 |
,| S-licarbazepine R-licarbazepine | 1.01 | 1.41 | 1.34 |
AUC0-∞ - the Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity
(NCT02281591)
Timeframe: Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.
| Intervention | ng.h/mL (Mean) |
|---|
| AUC0-∞ (BIA 2-194) | AUC0-∞ (BIA 2-195) | AUC0-∞ (Oxcarbazepine) |
|---|
| Eslicarbazepine Acetate | 271191 | 8816 | 3181 |
,| R-licarbazepine | 11003 | 66087 | 1073 |
,| S-licarbazepine | 132724 | 5417 | 2500 |
,| S-licarbazepine R-licarbazepine | 201409 | 116884 | 4726 |
AUC0-t - the Area Under the Plasma Concentration-time Curve to Last Measurable Time Point
(NCT02281591)
Timeframe: Phase A: pre-dose (Day 1); and ½, 1, 1½, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.Phase B: Days 6 to 10 inclusively: pre-dose. Day 11 (last dose): pre-dose; and ½, 1, 1½,2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 96 hours post-dose.
| Intervention | ng.h/mL (Mean) |
|---|
| AUC0-t (BIA 2-194) | AUC0-t (BIA 2-195) | AUC0-t (Oxcarbazepine) |
|---|
| Eslicarbazepine Acetate | 268045 | 6757 | 1947 |
,| R-licarbazepine | 9419 | 65203 | 422 |
,| S-licarbazepine | 130147 | 3074 | 748 |
,| S-licarbazepine R-licarbazepine | 198313 | 114635 | 3401 |
QTcI - QT Interval Individually Corrected for Heart Rate - Day 5
(NCT02283788)
Timeframe: -30 minutes (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 16, and 23.5 hours post-dose
| Intervention | msec (Mean) |
|---|
| 0.5 hr | 1 hour | 1.5 hours | 2 hours | 3 hours | 4 hours | 5 hours | 6 hours | 8 hours | 12 hours | 16 hours | 23.5 hours |
|---|
| BIA 2-093 1200 mg | -8.05 | -9.34 | -8.70 | -9.48 | -8.04 | -7.72 | -3.54 | -4.59 | -2.63 | -0.01 | -3.72 | -3.36 |
,| BIA 2-093 2400 mg | -6.15 | -7.34 | -8.67 | -8.31 | -8.50 | -6.16 | -1.71 | -2.64 | -1.36 | 0.03 | -4.65 | -0.06 |
,| Moxifloxacin 400 mg | -2.77 | 3.80 | 5.30 | 6.87 | 8.49 | 10.13 | 7.07 | 5.83 | 5.80 | 5.85 | 5.21 | 2.39 |
,| Placebo | -4.39 | -4.14 | -4.22 | -5.32 | -3.24 | -2.10 | -0.75 | -3.10 | -1.77 | -1.44 | -1.41 | -1.71 |
AUCτ - Cumulative Area Under the Plasma Concentration Time Curve Over the Dosing Interval at Steady State.
(NCT02283814)
Timeframe: Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h
| Intervention | ng.h/mL (Mean) |
|---|
| AUCτ (BIA 2-194) | AUCτ (BIA 2-195) |
|---|
| BIA 2-093 | 389794.3 | 22886.8 |
,| BIA 2-093 + TPM | 361733.9 | 19611.8 |
Tmax - the Time of Occurrence of Cmax
BIA 2-194 and BIA 2-195 are metabolites/active forms of eslicarbazepine acetate Both Groups A and B described in participant flow recieved BIA 2-093 and Topiramate. The results presented here are related with the different interventions in both groups (NCT02283814)
Timeframe: Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h
| Intervention | hours (Mean) |
|---|
| Tmax (BIA 2-194) | Tmax (BIA 2-195) |
|---|
| BIA 2-093 | 2.00 | 6.00 |
,| BIA 2-093 + TPM | 2.00 | 9.00 |
Cmax - the Maximum Plasma Concentration
BIA 2-194 and BIA 2-195 are metabolites/active forms of eslicarbazepine acetate (NCT02283814)
Timeframe: Time Frame: Group A:Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration; Group B: Day 8 and 27 within 5 minutes prior dosing and 0.25,0.5,0.75,1,1.33,1.67,2,2.5,3,4,6,9,12,16 and 24h
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-194) | Cmax (BIA 2-195) |
|---|
| BIA 2-093 | 25414.8 | 1062.6 |
,| BIA 2-093 + TPM | 21960.6 | 931.8 |
Cmax - the Maximum Plasma Concentration
BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate (NCT02283827)
Timeframe: Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-194) | Cmax (BIA 2-195) | Cmax (PHT) |
|---|
| BIA 2-093 | 23806.5 | 954.3 | 9405.1 |
,| BIA 2-093 + Phenytoin | 16350.6 | 976.9 | 12868.5 |
AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time
"AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time~BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate" (NCT02283827)
Timeframe: Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration
| Intervention | ng*h/mL (Mean) |
|---|
| AUC0-t (BIA 2-194) | AUC0-t (BIA 2-195) | AUC0-t (PHT) |
|---|
| BIA 2-093 | 371574.9 | 20675.0 | 186826.5 |
,| BIA 2-093 + Phenytoin (PHT) | 251055.2 | 19471.2 | 264784.8 |
Tmax - the Time of Occurrence of Cmax
BIA 2-194 and BIA 2-195 are metabolites of eslicarbazepine acetate (NCT02283827)
Timeframe: Day 8 and 27: within 5 minutes prior to dosing and 0.5,1,1.5,2,2.5,3,3.5,4,6,9,12,16 and 24 hours after drug administration
| Intervention | hours (Median) |
|---|
| Tmax (BIA 2-194) | Tmax (BIA 2-195) | Tmax (PHT) |
|---|
| BIA 2-093 | 2.50 | 9.00 | 4.00 |
,| BIA 2-093 + Phenytoin (PHT) | 3.00 | 9.00 | 4.00 |
Tmax BIA 2-005 - Time of Maximum Plasma Concentration of BIA 2-005
(NCT02283840)
Timeframe: prior to and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48 and 72 hours after drug administration
| Intervention | hours (Median) |
|---|
| Tmax (BIA 2-005) Test | Tmax (BIA 2-005) Reference |
|---|
| Cohort A:BIA 2-093 400 mg | 2.00 | 2.50 |
,| Cohort B:BIA 2-093 600 mg | 2.50 | 3.00 |
,| Cohort C:BIA 2-093 800 mg | 3.00 | 3.00 |
AUC0-t - the Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time
(NCT02283840)
Timeframe: prior to and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48 and 72 hours after drug administration
| Intervention | ng.h/mL (Mean) |
|---|
| AUC0-t (BIA 2-093) Test | AUC0-t (BIA 2-093) Reference |
|---|
| Cohort A:BIA 2-093 400 mg | 125739.8 | 122134.1 |
,| Cohort B:BIA 2-093 600 mg | 219560.8 | 215750.4 |
,| Cohort C:BIA 2-093 800 mg | 294749.1 | 293959.9 |
Cmax BIA 2-005 - the Maximum Plasma Concentration of BIA 2-005
(NCT02283840)
Timeframe: prior to and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 24, 48 and 72 hours after drug administration
| Intervention | ng/mL (Mean) |
|---|
| Cmax (BIA 2-005) Test | Cmax (BIA 2-005) Reference |
|---|
| Cohort A:BIA 2-093 400 mg | 7107.7 | 6660.3 |
,| Cohort B:BIA 2-093 600 mg | 10724.8 | 10404.5 |
,| Cohort C:BIA 2-093 800 mg | 13186.4 | 12767.6 |
Motor Reaction Time (MRT) (ms): Change From Baseline at Each Time Point During Acute Dosing Phase
(NCT02284828)
Timeframe: -1, 3, 6, and 10 hours post-dose
| Intervention | miliseconds (Mean) |
|---|
| 3 hours | 6 hours | 10 hours |
|---|
| Group 1 BIA 2-093 | 4.1 | 0.7 | -10.8 |
Motor Reaction Time (MRT) (ms): Raw Values at Each Time Point During Acute Dosing Phase
(NCT02284828)
Timeframe: -1, 3, 6, and 10 hours post-dose
| Intervention | miliseconds (Mean) |
|---|
| Pre-dose | 3 hours | 6 hours | 10 hours |
|---|
| Group 1 BIA 2-093 | 587.0 | 590.3 | 588.2 | 576.5 |
Recognition Reaction Time (RRT) (ms): Raw Values at Each Time Point During Acute Dosing Phase
(NCT02284828)
Timeframe: -1, 3, 6, and 10 hours post-dose
| Intervention | miliseconds (Mean) |
|---|
| Pre-dose | 3 hours | 6 hours | 10 hours |
|---|
| Group 1 BIA 2-093 | 425.0 | 414.0 | 419.3 | 408.0 |
Total Reaction Time (TRT) (ms): Raw Values at Each Time Point During Acute Dosing Phase
(NCT02284828)
Timeframe: -1, 3, 6, and 10 hours post-dose
| Intervention | miliseconds (Mean) |
|---|
| Pre-dose | 3 hours | 6 hours | 10 hours |
|---|
| Group 1 BIA 2-093 | 1011.9 | 1004.3 | 1007.5 | 984.5 |
Recognition Reaction Time (RRT) (ms): Change From Baseline at Each Time Point During Acute Dosing Phase
(NCT02284828)
Timeframe: -1, 3, 6, and 10 hours post-dose
| Intervention | miliseconds (Mean) |
|---|
| 3 hours | 6 hours | 10 hours |
|---|
| Group 1 BIA 2-093 | -11.1 | -9.2 | -19.3 |
Total Reaction Time (TRT) (ms): Change From Baseline at Each Time Point During Acute Dosing Phase
(NCT02284828)
Timeframe: -1, 3, 6, and 10 hours post-dose
| Intervention | miliseconds (Mean) |
|---|
| 3 hours | 6 hours | 10 hours |
|---|
| Group 1 BIA 2-093 | -7.0 | -8.4 | -30.0 |
Cmax (CBZ) - the Maximum Plasma Concentration
Reference - Day 28 following twice-daily oral administration of CBZ 400 mg Test - Day 35 following twice-daily oral administration of CBZ 400 mg (NCT02284854)
Timeframe: Day 28 to 35
| Intervention | ng/mL (Mean) |
|---|
| Cmax CBZ (D28 CBZ 400 mg twice-daily) | Cmax CBZ (D35 CBZ 400 mg twice-daily) |
|---|
| Group B | 10414 | 9719 |
AUC0-t (CBZE) - Area Under the Curve to Last Measurable Concentration for CBZE
"Reference - Day 28 following twice-daily oral administration of CBZ 400 mg Test - Day 35 following twice-daily oral administration of CBZ 400 mg~CBZE - carbamazepine-epoxide is the active metabolite of CBZ" (NCT02284854)
Timeframe: Day 28 to 35
| Intervention | ng*h/mL (Mean) |
|---|
| AUC0-t CBZE (D28 CBZ 400 mg twice-daily) | AUC0-t CBZE (D35 CBZ 400 mg twice-daily) |
|---|
| Group B | 15322 | 14953 |
Cmax (BIA 2-093) - the Maximum Plasma Concentration
Reference - Day 7 following once-daily oral administration of ESL 800 mg Test - Day 35 following once-daily oral administration of ESL 800 mg (NCT02284854)
Timeframe: Day 7 to 35
| Intervention | ng/mL (Mean) |
|---|
| Cmax ESL (D7 ESL 800mg) | Cmax ESL (D35 ESL 800mg) |
|---|
| Group A | 18601 | 14591 |
AUC0-t (CBZ) - Area Under the Curve to Last Measurable Concentration for CBZ
Reference - Day 28 following twice-daily oral administration of CBZ 400 mg Test - Day 35 following twice-daily oral administration of CBZ 400 mg (NCT02284854)
Timeframe: Day 28 to 35
| Intervention | ng*h/mL (Mean) |
|---|
| AUC0-t CBZ (D28 CBZ 400 mg twice-daily) | AUC0-t CBZ (D35 CBZ 400 mg twice-daily) |
|---|
| Group B | 104494 | 94394 |
Cmax (CBZE) - the Maximum Plasma Concentration
"Reference - Day 28 following twice-daily oral administration of CBZ 400 mg twice-daily Test - Day 35 following twice-daily oral administration of CBZ 400 mg twice-daily~CBZE - carbamazepine-epoxide is the active metabolite of CBZ" (NCT02284854)
Timeframe: Day 28 to 35
| Intervention | ng/mL (Mean) |
|---|
| Cmax CBZE (D28 CBZ 400 mg twice-daily) | Cmax CBZE (D35 CBZ 400 mg twice-daily) |
|---|
| Group B | 1562 | 1560 |
AUC0-t (BIA 2-093) - Area Under the Curve to Last Measurable Concentration for BIA 2-093
Reference - Day 7 following once-daily oral administration of ESL 800 mg Test - Day 35 following once-daily oral administration of ESL 800 mg (NCT02284854)
Timeframe: Day 7 to 35
| Intervention | ng*h/mL (Mean) |
|---|
| AUC0-t ESL (D7 ESL 800mg) | AUC0-t ESL (D35 ESL 800mg) |
|---|
| Group A | 276836 | 188648 |
AUC0-t - Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Sampling Time at Which Concentrations Were at or Above the Limit of Quantification
"Reference - MF - marketed formulation Test - TBM - to-be-marketed~BIA 2-005 - BIA 2-093 metabolite" (NCT02284880)
Timeframe: pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period
| Intervention | ng.hr/ml (Mean) |
|---|
| AUC0-t (BIA 2-005 Reference) | AUC0-t (BIA 2-005 Test) |
|---|
| 400 mg BIA 2-093 | 112568 | 108224 |
,| 800 mg BIA 2-093 | 279035 | 278734 |
Cmax - Maximum Plasma Concentration
Reference - MF - marketed formulation Test - TBM - to-be-marketed BIA 2-005 - BIA 2-093 metabolite (NCT02284880)
Timeframe: pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period
| Intervention | ng/ml (Mean) |
|---|
| Cmax (BIA 2-005 Reference) | Cmax (BIA 2-005 Test) |
|---|
| 400 mg BIA 2-093 | 6461 | 6547 |
,| 800 mg BIA 2-093 | 13183 | 12988 |
Tmax - Time of Occurrence of Cmax
"Reference - MF - marketed formulation Test - TBM - to-be-marketed~BIA 2-005 - BIA 2-093 metabolite" (NCT02284880)
Timeframe: pre-dose then 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose on each dosing period
| Intervention | hours (Median) |
|---|
| Tmax (BIA 2-005 Reference) | Tmax (BIA 2-005 Test) |
|---|
| 400 mg BIA 2-093 | 2.00 | 2.00 |
,| 800 mg BIA 2-093 | 2.00 | 1.75 |
AUCτ - Steady-state Area Under the Plasma Concentration-time Profile Over 24 h, the Dosing Interval
(NCT02287415)
Timeframe: PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose.
| Intervention | ng.h/mL (Mean) |
|---|
| Group 1 | 411834 |
Cmax - Maximum Steady-state Plasma Concentration
(NCT02287415)
Timeframe: PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose.
| Intervention | ng/mL (Mean) |
|---|
| Group 1 | 31652 |
Tmax - Time of Occurrence of Cmax
(NCT02287415)
Timeframe: PHASE A: first 3 days; PHASE B: Days 1, 2, 4, 6, 7 and 8: pre-dose. PHASE C: Days 1, 3, 5 and 7: pre-dose; Day 8: 24 h post last-warfarin dose.
| Intervention | hours (Median) |
|---|
| Group 1 | 6 |
AUC0-∞ (BIA 2-005)
AUC0-∞ (BIA 2-005) - the area under the plasma BIA 2-005 concentration versus time curve from time zero to infinity, calculated from AUC0-t + (Clast/λz), where Clast is the last quantifiable concentration and λz the apparent terminal rate constant; (BIA 2-005 is a BIA 2-093 metabolite) (NCT02288312)
Timeframe: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
| Intervention | ng.h/mL (Mean) |
|---|
| BIA 2-093 800 mg Fasting | 243808 |
| BIA 2-093 800 mg Fed | 236089 |
| BIA 2-093 800 mg (2 x 400 mg) | 244821 |
Tmax (BIA 2-005)
tmax (BIA 2-005) - the time of occurrence of Cmax of BIA 2-005 (BIA 2-005 is a BIA 2-093 metabolite) (NCT02288312)
Timeframe: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
| Intervention | hours (Mean) |
|---|
| BIA 2-093 800 mg Fasting | 2.64 |
| BIA 2-093 800 mg Fed | 2.75 |
| BIA 2-093 800 mg (2 x 400 mg) | 2.56 |
Cmax (BIA 2-005)
Cmax (BIA 2-005) - maximum observed plasma drug concentration of BIA 2-005 (BIA 2-093 metabolite) (NCT02288312)
Timeframe: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
| Intervention | ng/mL (Mean) |
|---|
| BIA 2-093 800 mg Fasting | 10973 |
| BIA 2-093 800 mg Fed | 11044 |
| BIA 2-093 800 mg (2 x 400 mg) | 11022 |
AUC0-t (BIA 2-005)
AUC0-t (BIA 2-005) - the area under the plasma concentration-time curve from time zero to the last sampling time at which BIA 2-005 concentrations are at or above the limit of quantification, calculated by the linear trapezoidal rule (BIA 2-005 is a BIA 2-093 metabolite) (NCT02288312)
Timeframe: pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours postdose.
| Intervention | ng.h/mL (Mean) |
|---|
| BIA 2-093 800 mg Fasting | 241651 |
| BIA 2-093 800 mg Fed | 234092 |
| BIA 2-093 800 mg (2 x 400 mg) | 242375 |
Profile of Mood States (POMS) Score.
"Participants were asked to rate the extent to which they feel a variety of emotions/feelings. The overall score is presented.~Assessments were performed prior to treatment (non-drug condition average) and at the end of each treatment period. Score range: -32 to 200. Lower scores correspond to better mood state." (NCT02912364)
Timeframe: Prior to treatment (non-drug condition average) and at the end of each six-week treatment period.
| Intervention | units on a scale (Mean) |
|---|
| Non-drug Condition Average | 8 |
| Eslicarbazepine | 11 |
| Carbamazepine | 15 |
MCG Paragraph Recall Scores.
"Participants were read a paragraph and were asked to recall content immediately following and twenty minutes after hearing the reading. MCG = Medical College of Georgia.~Assessments were performed prior to treatment (non-drug condition average) and at the end of each treatment period. Score range: 0 - 60, higher scores indicate better memory function." (NCT02912364)
Timeframe: Prior to treatment (non-drug condition average) and at the end of each six-week treatment period.
| Intervention | units on a scale (Mean) |
|---|
| Immediate Recall | Delayed Recall |
|---|
| Carbamazepine | 31 | 30 |
,| Eslicarbazepine | 33 | 31 |
,| Non-drug Condition Average | 34 | 33 |
Overall Composite Z Score of Neuropsychological Battery as a Measure of Direct Comparison of the 2 Antiepileptic Drugs.
Z score of cognitive tests at end of each 6-week drug treatment period for each intervention (i.e., Eslicarbazepine and Carbamazepine). The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poor cognitive performance compared to the mean and positive numbers represent higher cognitive performance compared to the mean. (NCT02912364)
Timeframe: At the end of each 6-week drug treatment period.
| Intervention | Z-score (Mean) |
|---|
| Eslicarbazepine | .001 |
| Carbamazepine | -.23 |
Dual Task Percent of Time in Box.
"Participants were asked to use their computer mouse to keep the cursor inside a moving box on the computer screen while simultaneously responding with a button press when a number on the screen exceeded a certain value.~Assessments were performed prior to treatment (non-drug condition average) and at the end of each treatment period." (NCT02912364)
Timeframe: Prior to treatment (non-drug condition average) and at the end of each six-week treatment period.
| Intervention | percentage of time in box (Mean) |
|---|
| Non-drug Condition Average | 62 |
| Eslicarbazepine | 62 |
| Carbamazepine | 60 |
Overall Z-score for Executive Function.
Executive function consists of a composite of measures from the computerized cognitive tests. The Z-score indicates the number of standard deviations away from a reference population. A Z-score of 0 is equal to the mean. Negative numbers indicate poor cognitive performance compared to the mean and positive numbers represent higher cognitive performance compared to the mean. (NCT02912364)
Timeframe: At the end of each 6-week drug treatment period.
| Intervention | Z-score (Mean) |
|---|
| Eslicarbazepine | .22 |
| Carbamazepine | -.32 |
The Number of Subjects Completing 24 Weeks Adjunctive Therapy During Maintenance Phase
Phase 4 study of eslicarbazepine acetate (ESL) as adjunctive therapy in adult subjects with a diagnosis of epilepsy with Partial-onset seizures (POS). Two groups of ESL-naïve subjects will be evaluated (NCT03116828)
Timeframe: From the date of the first dose of the study drug until the completion of 24 weeks Maintenance Phase
| Intervention | participants (Number) |
|---|
| Eslicarbazepine Acetate (Arm 1) | 36 |
| Eslicarbazepine Acetate (Arm 2) | 37 |