Efficacy and Safety of Adjunctive Perampanel for the Treatment of Partial-onset Seizures

19 Oct, 21

Introduction

Perampanel is a non-competitive ?-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, use as an adjunctive for the treatment of has been partial onset seizure.

Aim

To ascertain the efficacy and safety of once-daily 8 or 12 mg perampanel, given as an adjunctive with other antiepileptic drugs (AEDs) for the treatment of drug-resistant partial-onset seizures

Patient Profile

Patients (age ≥12 years) diagnosed with partial onset seizures, with or without secondary generalization (n=388)
The study participants either had failed ≥2 AEDs, or ≥5 seizures at baseline and were already on stable doses of up to 3 approved AEDs

Methods

Study Design

A multinational, double-blind, placebo-controlled trial phase III trial

Treatment Strategy

Patients were randomized (1:1:1) to once-daily perampanel 8 mg (n=133), 12 mg (n=134), or placebo (n=121).
Following a 6-week baseline period, patients entered a 19-week double-blind phase that included a 6-week titration period (2 mg/week increments to achieve the target dose) followed by a 13-week maintenance period.

Assessments

Treatment efficacy was assessed using patient diaries, Clinical and Patient Global Impression of Change (CGIC/PGIC), and the Quality of Life in Epilepsy questionnaire (QOLIE-31-P).

Outcomes

Efficacy Outcomes

Percent change in seizure frequency per 28 days (from baseline to the end of 19-week double-blind phase)
≥50%reduction in seizure frequency from baseline (50% responder rate)

Safety Outcomes

Adverse events (AEs)
Treatment withdrawals

Results

The trial was completed by 320 (82.5%) participants.
As per an intention-to-treat analysis, compared with placebo, the median percent change in seizure frequency was significantly greater for patients treated with perampanel 12 mg, and 8 mg (Fig. 1).

Fig. 1: Median change in seizure frequency in the study groups

Fifty percent responder rates during the maintenance period were significantly higher for patients treated with perampanel 8 mg and 12 mg, versus those treated with placebo (Table 1).

Table 1: 50% Responder rates in the study groups

Parameter	Placebo Group	Perampanel 8 mg Group	Perampanel 12 mg Group
50% Responder Rate	26.4%	37.6%	36.1%

The difference between the 50% responder rates for patients treated with perampanel 8 mg and 12 mg was not statistically significant.
Discontinuation of treatment was seen in 68 (17.5%) patients; of these, 40 discontinuations (10.3%) were attributed to AEs.
Most frequent treatment-emergent AEs comprised dizziness, somnolence, irritability, headache, fall, and ataxia.

Conclusions

Once-daily, adjunctive perampanel at doses of 8 or 12 mg improved seizure control in patients with uncontrolled partial-onset seizures.
Perampanel 8 and 12 mg exhibited an acceptable safety, and tolerability profile.

Neurology. 2012;79:589–596.