Pregabalin for the management of partial epilepsy

Figures & data

Table 1 Overview of randomized placebo-controlled double-blind trials of pregabalin in patients with refractory partial-onset seizures, with or without secondary generalization

Study	Total pregabalin dose (mg/day)	Frequency of administrationa	Titration period	Trial duration	Number of patients (ITT)
French et al 2003	50	bid	None	8 weeks baseline	453
	150	bid		12 weeks double-blind
	300	bid
	600	bid
Arroyo et al 2004	150	tid	1 week	8 weeks baseline	287
	600	tid		12 weeks double-blind
Beydoun et al 2005	600	bid	1 week	8 weeks baseline	312
	600	tid		12 weeks double-blind
Elger et al 2005	Fixed 600	bid	None	6 weeks baseline	341
	Flexible 150–600	bid	Flexible 12 weeks	12 weeks double-blind

a bid, twice daily; tid, three times daily.

Figure 1 Trial design used in a pregabalin randomized flexible-dose (150–600 mg/day) versus fixed-dose (600 mg/day) double-blind adjunctive-therapy trial in patients with refractory partial-onset seizures, with or without secondary generalization. Adapted from Elger et al 2005.

Figure 2 Seizure reduction in short-term fixed-dose pregabalin adjunctive therapy studies. Dose response relationship for seizure reduction (shown as response ratio [RRatio] on right y axis and percent change from baseline as calculated from RRatio on left y-axis) is shown for each of the three short-term fixed-dose pregabalin studies (French et al 2000; Arroyo et al 2004; Beydoun et al 2005). P values shown represent a significant difference from placebo in the same study. Adapted from Brodie et al 2004.

Figure 3 Responder rates (proportion of patients with ≥50% reduction in seizure frequency compared with baseline) in each of four randomized adjunctive-therapy double-blind trials of pregabalin in patients with refractory partial-onset seizures, with or without secondary generalization. The first three trials (French et al 2003; Arroyo et al 2004; Beydoun et al 2005) included fixed-dose pregabalin treatment groups whilst the fourth trial (Elger et al 2005) included both flexible-dose (150–600 mg/day) and fixed-dose (600 mg/day) groups. *Significantly different from placebo in the same study.

Abbreviations: PGB, pregabalin; PBO, placebo.

Table 2 Seizure freedom rates in patients treated with long-term adjunctive-therapy pregabalin

Elapsed time between last seizure and final observation	All patients, all data			Data up to initial requalificationa
	Number assessed	Number seizure-free	% seizure-free	Number assessed	Number seizure-free	% seizure-free
At least 1 month	1423	311	21.9%	1115	219	19.6%
At least 2 months	1361	203	14.9%	1064	145	13.6%
At least 3 months	1300	156	12.0%	1018	105	10.3%
At least 4 months	1250	128	10.2%	984	83	8.4%
At least 6 months	1119	103	9.2%	892	69	7.7%
At least 1 year	877	71	8.1%	710	26	3.7%
At least 2 years	511	42	8.2%	192	6	3.1%
At least 3 years	354	26	7.3%	59	1	1.7%

Notes: Results are pooled data from four open-label studies using both the entire ITT population (all data) and the ITT population with only data obtained before a patient’s initial requalification.

a Patients from the US were required to undergo requalification to determine eligibility to continue in the trial, and only data collected prior to initial requalification were included for these patients (see text). For unaffected patients, data for the entire open-label treatment period were included.

Table 3 Most common adverse events reported in randomized placebo-controlled double-blind trials of pregabalin in patients with refractory partial-onset seizures, with or without secondary generalization

	Frequency (%)
	Pregabalin daily dose
Adverse event	50 mg	150 mg	300 mg	600 mg	Flexible, 150–600 mg	Placebo
	n = 88	n = 187	n = 90	n = 533	n = 131	n = 294
Dizziness	9.1	17.6	31.1	33.8	24.4	10.5
Somnolence	10.2	11.2	17.8	25.5	19.1	10.9
Ataxia	3.4	5.9	10	19.9	9.2	4.1
Fatigue	5.7	10.7	12.2	18	16.8	8.2
Headache	6.7	7.5	5.6	10.1	13.7	11.6
Weight gaina	1.1	4.8	6.7	17.1	19.1	1.4
Withdrawal for adverse events	6.9	5.9	14.4	24.2	12.2	6.3

Notes: Data were pooled from four studies (French et al 2003; Arroyo et al 2004; Beydoun et al 2005; Elger et al 2005). Some patients reported >1 adverse event.

a Weight gain spontaneously reported as an adverse event by patient.

Figure 4 Kaplan-Meier analysis of time to discontinuation due to adverse events with flexible (150–600 mg/day) versus fixed (600 mg/day) pregabalin dosing. Patients in the fixed-dose group discontinued from the study due to adverse events earlier than those in the flexible-dose group. Adapted from Elger et al 2005.

Table 4 Most common adverse events (reported by ≥10% of all patients) among 1480 patients treated with long-term adjunctive-therapy pregabalin based on pooled data from 4 open-label studies

Adverse event	Frequency (%)	Withdrawals due to event (%)
Dizziness	33.9	1.4
Accidental injury	28.6	0.3
Somnolence	27.4	1.7
Weight gaina	23.6	2.0
Infection	22.4	0
Headache	20.0	0.6
Asthenia	19.9	1.2
Pain	17.8	0.1
Ataxia	14.3	0.8
Amblyopia	14.1	0.5
Diplopia	11.8	0.2
Thinking abnormalb	11.7	0.9
Nausea	10.5	0.6

a Weight gain spontaneously reported as an adverse event by patient.

b Coded term used to indicate difficulties with attention or concentration.

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