The Experts below are selected from a list of 129 Experts worldwide ranked by ideXlab platform

Virinder Nohria - One of the best experts on this subject based on the ideXlab platform.

  • safety and tolerability of different titration rates of retigabine ezogabine in patients with partial onset seizures
    Epilepsy Research, 2013
    Co-Authors: Victor Biton, Martin J Brodie, Sarah E Derossett, Antonio Gilnagel, Virinder Nohria
    Abstract:

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated Potassium-Channel KCNQ2–5 (Kv 7.2–7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N = 73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300 mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150 mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200 mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p = 0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p = 0.010) but not in the medium-titration group (p = 0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

  • Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.
    Epilepsy research, 2013
    Co-Authors: Victor Biton, Antonio Gil-nagel, Martin J Brodie, Sarah E Derossett, Virinder Nohria
    Abstract:

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated Potassium-Channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p=0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

Victor Biton - One of the best experts on this subject based on the ideXlab platform.

  • safety and tolerability of different titration rates of retigabine ezogabine in patients with partial onset seizures
    Epilepsy Research, 2013
    Co-Authors: Victor Biton, Martin J Brodie, Sarah E Derossett, Antonio Gilnagel, Virinder Nohria
    Abstract:

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated Potassium-Channel KCNQ2–5 (Kv 7.2–7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N = 73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300 mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150 mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200 mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p = 0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p = 0.010) but not in the medium-titration group (p = 0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

  • Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.
    Epilepsy research, 2013
    Co-Authors: Victor Biton, Antonio Gil-nagel, Martin J Brodie, Sarah E Derossett, Virinder Nohria
    Abstract:

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated Potassium-Channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p=0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

Sarah E Derossett - One of the best experts on this subject based on the ideXlab platform.

  • safety and tolerability of different titration rates of retigabine ezogabine in patients with partial onset seizures
    Epilepsy Research, 2013
    Co-Authors: Victor Biton, Martin J Brodie, Sarah E Derossett, Antonio Gilnagel, Virinder Nohria
    Abstract:

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated Potassium-Channel KCNQ2–5 (Kv 7.2–7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N = 73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300 mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150 mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200 mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p = 0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p = 0.010) but not in the medium-titration group (p = 0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

  • Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.
    Epilepsy research, 2013
    Co-Authors: Victor Biton, Antonio Gil-nagel, Martin J Brodie, Sarah E Derossett, Virinder Nohria
    Abstract:

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated Potassium-Channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p=0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

Martin J Brodie - One of the best experts on this subject based on the ideXlab platform.

  • safety and tolerability of different titration rates of retigabine ezogabine in patients with partial onset seizures
    Epilepsy Research, 2013
    Co-Authors: Victor Biton, Martin J Brodie, Sarah E Derossett, Antonio Gilnagel, Virinder Nohria
    Abstract:

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated Potassium-Channel KCNQ2–5 (Kv 7.2–7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N = 73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300 mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150 mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200 mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p = 0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p = 0.010) but not in the medium-titration group (p = 0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

  • Safety and tolerability of different titration rates of retigabine (ezogabine) in patients with partial-onset seizures.
    Epilepsy research, 2013
    Co-Authors: Victor Biton, Antonio Gil-nagel, Martin J Brodie, Sarah E Derossett, Virinder Nohria
    Abstract:

    Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated Potassium-Channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset seizures receiving concomitant AEDs were randomized to one of three titration groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal doses. Fast-, medium-, and slow-titration groups received dose increments of 150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of 1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were performed throughout. Discontinuation rates due to treatment-emergent adverse events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22) titration groups than in the slow-titration group (3/23) but statistical significance was achieved only for the high-titration group compared with the low-titration group (p=0.024). Stratified analysis, with concomitant AEDs divided into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers, showed that the risk of discontinuation due primarily to TEAEs was significantly higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078) when compared with the slow-titration group. Overall, the slow-titration rate appeared to be best tolerated and was used in further efficacy and safety studies with RTG/EZG.

Bernd A. Neubauer - One of the best experts on this subject based on the ideXlab platform.

  • Sodium and Potassium Channel dysfunctions in rare and common idiopathic epilepsy syndromes.
    Brain & development, 2009
    Co-Authors: Andreas Hahn, Bernd A. Neubauer
    Abstract:

    Abstract Mutations in the SCN1A gene are found in up to 80% of individuals with severe myoclonic epilepsy of infancy (SMEI), and mutations in KCNQ2 and KCNQ3 were identified in benign familial neonatal convulsions (BFNC) as well as in single families with Rolandic epilepsy (RE) and idiopathic generalized epilepsies (IGE). This paper summarizes recent findings concerning sodium (SCN1A) and Potassium Channel (KCNQ2 and KCNQ3) dysfunctions in the pathogenesis of rare and common idiopathic epilepsies (IE). SMEI, severe idiopathic generalized epilepsy of infancy (SIGEI), and myoclonic–astatic epilepsy (MAE) are rare IE. Because of some semeiologic overlap, a comparative analysis of the SCN1A gene performed in 20 patients with MAE and in 18 with SIGEI. This revealed mutations in three subjects with SIGEI only. Since BFNC are over-represented in families with RE, a mutational analysis was performed in 58 families with RE with and without BNFC. This revealed functionally relevant mutations in two index cases with BNFC, and three missense mutations (one resulting in a significantly reduced Potassium current amplitude) in three patients with RE, but without BNFC. One KCNQ3 missense variant was also detected in eight out of 455 IGE patients but not in 454 controls, and a silent KCNQ2-SNP was found over-represented in both epilepsy samples. These findings confirm that mutations in the SCN1A gene are mainly involved in the pathogenesis of SMEI, rarely in that of SIGEI, and are commonly not found in patients with MAE. They also demonstrate that sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common IE syndromes.

  • Review article Sodium and Potassium Channel dysfunctions in rare and common idiopathic epilepsy syndromes
    2009
    Co-Authors: Andreas Hahn, Bernd A. Neubauer
    Abstract:

    Mutations in the SCN1A gene are found in up to 80% of individuals with severe myoclonic epilepsy of infancy (SMEI), and mutations in KCNQ2 and KCNQ3 were identified in benign familial neonatal convulsions (BFNC) as well as in single families with Rolandic epilepsy (RE) and idiopathic generalized epilepsies (IGE). This paper summarizes recent findings concerning sodium (SCN1A) and Potassium Channel (KCNQ2 and KCNQ3) dysfunctions in the pathogenesis of rare and common idiopathic epilepsies (IE). SMEI, severe idiopathic generalized epilepsy of infancy (SIGEI), and myoclonic–astatic epilepsy (MAE) are rare IE. Because of some semeiologic overlap, a comparative analysis of the SCN1A gene performed in 20 patients with MAE and in 18 with SIGEI. This revealed mutations in three subjects with SIGEI only. Since BFNC are over-represented in families with RE, a mutational analysis was performed in 58 families with RE with and without BNFC. This revealed functionally relevant mutations in two index cases with BNFC, and three missense mutations (one resulting in a significantly reduced Potassium current amplitude) in three patients with RE, but without BNFC. One KCNQ3 missense variant was also detected in eight out of 455 IGE patients but not in 454 controls, and a silent KCNQ2-SNP was found over-represented in both epilepsy samples. These findings confirm that mutations in the SCN1A gene are mainly involved in the pathogenesis of SMEI, rarely in that of SIGEI, and are commonly not found in patients with MAE. They also demonstrate that sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common IE syndromes. Published by Elsevier B.V.