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Review of clinical studies of perampanel in adolescent patients

View Article: PubMed Central - PubMed

ABSTRACT

Aim: To assess the clinical trial and real‐world data for adjunctive perampanel in adolescents and develop consensus recommendations to guide the use of perampanel in this population in clinical practice.

Methods: In May 2015, 15 epilepsy experts attended a Consensus Development Meeting to assess the clinical trial data for perampanel, specific to the adolescent age group (12‐17 years) and develop consensus treatment recommendations.

Results and discussion: Analysis of the adolescent subgroup data of three pivotal placebo‐controlled, double‐blind, phase 3 trials investigating perampanel in patients with ongoing focal epileptic seizures despite receiving one to three antiepileptic drugs found that perampanel 4–12 mg was superior to placebo. The tolerability profile of perampanel was generally acceptable. Adolescent patients receiving long‐term treatment with perampanel in an open‐label extension study maintained improvements in seizure control compared with baseline, with a favorable risk‐benefit profile. A phase 2 study showed that perampanel had no clinically important effects on cognitive function, growth, and development.

Conclusion: Perampanel is a welcome addition to the armamentarium of existing antiepileptic drugs as it represents a new approach in the management of epilepsy, with a novel mechanism of action, and the potential to have a considerable impact on the treatment of adolescents with epilepsy.

No MeSH data available.


Design of a phase 2 study of perampanel (study 235) (Hussein et al. 2015; Pina‐Garza et al. 2015; Renfroe et al. 2015). R, randomization. 1All patients were retained to the last visit of extension part A. 2Part B was optional (a patient proceeded to or completed part B if perampanel was not commercially available or extended‐access program 401 was not in place in their country of residence). 3Follow‐up was conducted for all patients 4 weeks after their last on‐treatment visit.
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brb3505-fig-0002: Design of a phase 2 study of perampanel (study 235) (Hussein et al. 2015; Pina‐Garza et al. 2015; Renfroe et al. 2015). R, randomization. 1All patients were retained to the last visit of extension part A. 2Part B was optional (a patient proceeded to or completed part B if perampanel was not commercially available or extended‐access program 401 was not in place in their country of residence). 3Follow‐up was conducted for all patients 4 weeks after their last on‐treatment visit.

Mentions: Three multinational, multicenter, double‐blind, randomized, placebo‐controlled, phase 3 trials (studies 304 [NCT00699972] (French et al. 2012), 305 [NCT00699582] (French et al. 2013) and 306 [NCT00700310] (Krauss et al. 2012); Fig. 1), comprising a study population of adults and adolescents (age 12–17 years) were done to establish the minimum effective dose and the dose range (2–12 mg) of once‐daily perampanel. Patients with refractory epilepsy who were taking one to three approved antiepileptic drugs (AEDs) at baseline, but were still having uncontrolled partial‐onset seizures were enrolled. Study 306 assessed the low to middle dose range (2, 4, and 8 mg) (Krauss et al. 2012). The two other trials, studies 304 and 305, had identical methodology and assessed the higher daily doses of 8 and 12 mg (French et al. 2012, 2013). Study 307 (NCT00735397) was an open‐label extension study of patients completing the double‐blind phase of the three pivotal phase 3 trials (Krauss et al. 2013). Another recent placebo‐controlled phase 2 study was designed to determine the effect of perampanel on cognition, growth, safety, tolerability, and pharmacokinetics (PK) in adolescents (study 235; NCT01161524; Fig. 2; Hussein et al. 2015; Pina‐Garza et al. 2015; Renfroe et al. 2015). An observational retrospective multicenter survey provided real‐world clinical data on the effectiveness and tolerability of perampanel in children and adolescents (age 2–17 years) with refractory epilepsy (Biró et al. 2015).


Review of clinical studies of perampanel in adolescent patients
Design of a phase 2 study of perampanel (study 235) (Hussein et al. 2015; Pina‐Garza et al. 2015; Renfroe et al. 2015). R, randomization. 1All patients were retained to the last visit of extension part A. 2Part B was optional (a patient proceeded to or completed part B if perampanel was not commercially available or extended‐access program 401 was not in place in their country of residence). 3Follow‐up was conducted for all patients 4 weeks after their last on‐treatment visit.
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brb3505-fig-0002: Design of a phase 2 study of perampanel (study 235) (Hussein et al. 2015; Pina‐Garza et al. 2015; Renfroe et al. 2015). R, randomization. 1All patients were retained to the last visit of extension part A. 2Part B was optional (a patient proceeded to or completed part B if perampanel was not commercially available or extended‐access program 401 was not in place in their country of residence). 3Follow‐up was conducted for all patients 4 weeks after their last on‐treatment visit.
Mentions: Three multinational, multicenter, double‐blind, randomized, placebo‐controlled, phase 3 trials (studies 304 [NCT00699972] (French et al. 2012), 305 [NCT00699582] (French et al. 2013) and 306 [NCT00700310] (Krauss et al. 2012); Fig. 1), comprising a study population of adults and adolescents (age 12–17 years) were done to establish the minimum effective dose and the dose range (2–12 mg) of once‐daily perampanel. Patients with refractory epilepsy who were taking one to three approved antiepileptic drugs (AEDs) at baseline, but were still having uncontrolled partial‐onset seizures were enrolled. Study 306 assessed the low to middle dose range (2, 4, and 8 mg) (Krauss et al. 2012). The two other trials, studies 304 and 305, had identical methodology and assessed the higher daily doses of 8 and 12 mg (French et al. 2012, 2013). Study 307 (NCT00735397) was an open‐label extension study of patients completing the double‐blind phase of the three pivotal phase 3 trials (Krauss et al. 2013). Another recent placebo‐controlled phase 2 study was designed to determine the effect of perampanel on cognition, growth, safety, tolerability, and pharmacokinetics (PK) in adolescents (study 235; NCT01161524; Fig. 2; Hussein et al. 2015; Pina‐Garza et al. 2015; Renfroe et al. 2015). An observational retrospective multicenter survey provided real‐world clinical data on the effectiveness and tolerability of perampanel in children and adolescents (age 2–17 years) with refractory epilepsy (Biró et al. 2015).

View Article: PubMed Central - PubMed

ABSTRACT

Aim: To assess the clinical trial and real‐world data for adjunctive perampanel in adolescents and develop consensus recommendations to guide the use of perampanel in this population in clinical practice.

Methods: In May 2015, 15 epilepsy experts attended a Consensus Development Meeting to assess the clinical trial data for perampanel, specific to the adolescent age group (12‐17 years) and develop consensus treatment recommendations.

Results and discussion: Analysis of the adolescent subgroup data of three pivotal placebo‐controlled, double‐blind, phase 3 trials investigating perampanel in patients with ongoing focal epileptic seizures despite receiving one to three antiepileptic drugs found that perampanel 4–12 mg was superior to placebo. The tolerability profile of perampanel was generally acceptable. Adolescent patients receiving long‐term treatment with perampanel in an open‐label extension study maintained improvements in seizure control compared with baseline, with a favorable risk‐benefit profile. A phase 2 study showed that perampanel had no clinically important effects on cognitive function, growth, and development.

Conclusion: Perampanel is a welcome addition to the armamentarium of existing antiepileptic drugs as it represents a new approach in the management of epilepsy, with a novel mechanism of action, and the potential to have a considerable impact on the treatment of adolescents with epilepsy.

No MeSH data available.