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Pregabalin as adjunctive therapy in adult and pediatric patients with generalized tonic-clonic seizures: A
Joseph Driscoll1, Mary Almas2, Gabriela Gregorian1
1Pfizer Inc, Groton, CT, USA.
Insights
Pregabalin did not effectively reduce generalized tonic-clonic (GTC) seizures in adults and children. The medication was generally well-tolerated, with a safety profile consistent with existing data.
Area of Science:
- Neurology
- Clinical Pharmacology
Background:
- Generalized tonic-clonic (GTC) seizures are a common epilepsy manifestation, particularly in children.
- Effective adjunctive therapies for GTC seizures are crucial for improving patient outcomes.
Purpose of the Study:
- To evaluate the efficacy and safety of pregabalin as adjunctive therapy for GTC seizures in pediatric and adult patients.
- To determine if pregabalin significantly reduces seizure frequency compared to placebo.
Main Methods:
- A randomized, double-blind, multicenter, phase 3 study involving 219 patients (aged 5-65 years).
- Patients received adjunctive pregabalin (5 mg/kg/day or 10 mg/kg/day) or placebo for 10 weeks.
- The primary endpoint was the change in log-transformed 28-day GTC seizure rate.
Main Results:
- Adjunctive pregabalin at both dosages did not result in a significant reduction in GTC seizure rates compared to placebo in adults or children.
- Responder rates (≥50% seizure reduction) were not significantly different between pregabalin and placebo groups.
- The most common adverse events were dizziness, headache, and somnolence, mostly mild to moderate.
Conclusions:
- Adjunctive pregabalin is not effective in reducing GTC seizure frequency in adults and children with epilepsy.
- Pregabalin demonstrated a well-tolerated safety profile, consistent with known data, with few treatment discontinuations due to adverse events.
Objective:
Generalized tonic-clonic (GTC) seizures are the most common type of generalized seizure and more common in children than adults. This phase 3 study evaluated the efficacy and safety of pregabalin for GTC seizures in adults and children with epilepsy.
Methods:
This randomized, double-blind, multicenter study evaluated pregabalin (5 mg/kg/day or 10 mg/kg/day) vs placebo as adjunctive therapy for 10 weeks (following a 2-week dose escalation), in pediatric and adult patients (aged 5-65 years) with GTC seizures. Primary endpoint was change in log-transformed 28-day seizure rate during active treatment. Secondary endpoints included responder rates, defined as proportion of patients with ≥50% reduction in 28-day GTC seizure rate from baseline. Safety was monitored throughout.
Results:
Of 219 patients, 75, 72, and 72 were randomized to adjunctive pregabalin 5 mg/kg/day, 10 mg/kg/day, and placebo, respectively. Fifteen, 11, and 6 patients discontinued from the 5 mg/kg/day, 10 mg/kg/day, and placebo arms, respectively, most commonly due to adverse events (AEs; 10.7%, 6.9%, and 5.6%, respectively). A nonsignificant change in log-transformed mean 28-day seizure rate was seen with pregabalin 10 mg/kg/day vs placebo (least-squares [LS] mean difference -0.01 [95% confidence interval (CI) -0.19 to 0.16]; P = .8889) and with pregabalin 5 mg/kg/day vs placebo (LS mean difference 0.02 [CI -0.15 to 0.19]; P = .8121). Similar observations were noted for adults and children. No significant differences were seen for secondary endpoints with pregabalin vs placebo, including responder rate. The most common AEs (≥10%) were dizziness, headache, and somnolence. Most were of mild/moderate intensity. Seven patients had serious AEs, with one death in the placebo arm (sudden unexpected death in epilepsy).
Significance:
Adjunctive pregabalin treatment did not change GTC seizure rate in adults or children. The safety profile of pregabalin was similar to that known; treatment was well tolerated with few discontinuations due to AEs.
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