Dose-Response Trial of Pregabalin Add-On Therapy in Patients with Partial Seizures
Abstract number :
L.05
Submission category :
Year :
2000
Submission ID :
394
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Jacqueline A French, Michael JR Malicsi, Alan R Kugler, Lloyd E Knapp, Kathryn A Laughlin, Howard N Bockbrader, Susan K Romine, Jeffery L Robbins, Elizabeth A Garofalo, Pregabalin 1008-034/-035 Study Group, Univ of Pennsylvania, Philadelphia, PA; Pfizer G
RATIONALE: Pregabalin, an analogue of the mammalian neurotransmitter GABA, is a novel CNS compound with anticonvulsant activity. This trial evaluated the dose-response relationship of efficacy and safety of pregabalin administered twice-daily (BID) as add-on treatment in reducing seizure frequency in patients with partial seizures. METHODS:_ This 80-center, double-blind, parallel-group study consisted of an 8-week baseline and a 12-week double-blind phase. Eligible patients on 1-3 AEDs were randomized to 1 of 5 treatment groups (50, 150, 300, and 600 mg/day pregabalin or placebo administered BID) with no titration. Efficacy assessments evaluated partial seizure frequency reductions from baseline using symmetrized percent change (RRatio) and responder rate (? 50% seizure reduction). Pharmacokinetic parameters were estimated. RESULTS: There were 453 ITT patients. Median baseline seizure rate was 10/month. Seizure reductions from baseline were 7, 12, 34, 44, and 54%, responder rates were 14, 15, 31, 40, and 51%, and withdrawal rates due to adverse events were 5, 7, 1, 14, and 24% for the placebo (n=100), 50 (n=88), 150 (n=86), 300 (n=90), and 600 (n=89) mg/day pregabalin groups, respectively. The 150, 300, and 600 mg/day pregabalin groups showed statistically significantly greater reductions in seizures (p?0.0001) and greater responder rates compared to the placebo group. There was a favorable and statistically significant (p?0.001) dose-response trend in RRatio and responder rate. Pregabalin was well tolerated. Dizziness and somnolence were the most common adverse events, and their incidence was dose-related. Pregabalin pharmacokinetics are dose-proportional and predictable. CONCLUSIONS: Pregabalin 150, 300, and 600 mg/day administered BID are all highly effective as add-on therapy when compared to placebo, exhibiting a clear dose-response in seizure frequency reduction and responder rate. Pregabalin treatment was well tolerated. These results indicate pregabalin may be initiated without titration at 150 mg/day administered BID. Dosage may be increased subsequently based upon individual patient response and tolerability.