Abstracts

RATIONALE: Dosing guidelines for the selective GABA reuptake inhibitor (SGRI) tiagabine HCl (GABITRIL[reg]) state that treatment should be initiated at 4 mg once daily and increased 4-8 mg weekly until clinical response is achieved. It has been theorized that a titration schedule of 2 mg every 3-4 days would allow for a patient to achieve the desirable clinical response more rapidly, while being equally tolerable. The purpose of this study was to evaluate the safety and compliance of 2 dosage strengths of tiagabine with different titration schedules when used as add-on therapy. This presentation will inform participants about the usefulness and safety of the following dosing schedule for tiagabine:2 mg/3-4 days.
METHODS: A multicenter, randomized, parallel-group, open-label, 28-day trial enrolled subjects with partial seizures, with or without secondary generalization, who continued to receive stable doses of other anticonvulsants. Subjects randomized to the standard regimen group received one 4-mg tablet of tiagabine during Week 1 and then the dosage (given BID) was increased by 4 mg/week to reach the 16 mg target daily dose. Subjects randomized to the contrast regimen group received one 4-mg tablet of tiagabine on Day 1 and one 2-mg tablet of tiagabine BID on Days 2-7. The dosage (given BID) was increased by one 2-mg tablet every 3-4 days to reach 16 mg/day target daily dose. Pills dispensed to and returned by each patient were counted, and compliance was defined as taking at least 70% of the study medication. Adverse events (AEs) were collected throughout the study.
RESULTS: Of the 412 subjects randomized, 410 were evaluated for safety (222 subjects in the standard regimen group and 188 subjects in the contrast regimen group). Eighty-six percent (86%) of the 222 subjects in the standard regimen group and 84% of the 188 subjects in the contrast regimen group completed the 28-day study. Seventy-six percent (76%) of patients in the standard regimen group and 79% of patients in the contrast regimen group reached the target daily dose of 16 mg by Day 28. Eighty-five percent (85%) of subjects in both groups were compliant to the treatment regimen. Similar percentages of subjects in the standard regimen and contrast regimen groups reported one or more AEs (49% vs 45%, respectively). The most common, treatment-emergent AEs reported by subjects in the standard and contrast regimen groups were dizziness (13% and 11%, respectively), headache (7%, 6%), somnolence (7%, 5%), nausea (6%, 2%), and asthenia (5%, 7%); most AEs were mild to moderate in nature. Few subjects in either treatment groups discontinued due to AEs (10% of patients in the standard regimen group vs. 11% of patients in the contrast regimen group).
CONCLUSIONS: In this large, clinical trial of the SGRI tiagabine, both dosage strengths with different titration schedules (2 mg/3-4 days and 4 mg/7 days) were well tolerated in a BID dosing regimen. Both doses and corresponding titration schedules were associated with high patient compliance (85%). Since the titration rate of 2 mg increase every 3-4 days is more flexible, patients may be able to achieve the desired clinical response earlier in the treatment course.
[Supported by: Cephalon, Inc. and Abbott Laboratories.]; (Disclosure: Grant - Abbott, Cephalon, Honoraria - Speaker bureau, Abbott, Cephalon)