BACKGROUND: To make it easier for patients who are prescribedzonisamide to administer their medicine, a rapidly disintegrating oral tablet formulation has been developed. OBJECTIVE: These 2 trials assessed the bioequiva-lence of a new orally dispersible tablet formulation of zonisamide (test) versus an immediate-release reference capsule. METHODS: Study 1 assessed the bioequivalence of a 100-mg orally dispersible tablet versus a 100-mg reference capsule. Study 2 assessed the bioequivalence of a 300-mg test tablet versus three 100-mg reference capsules. Both trials were open-label, randomized-sequence, single-dose, 2-period, 2-treatment crossover studies in consenting healthy male volunteers aged 18 to 55 years. A 4-week washout separated treatment periods. The zonisamide test tablet was placed on the tongue and, after it had dispersed in saliva, swallowed without water. Zonisamide serum concentrations were analyzed using a validated high-performance liquid chromatography assay with tandem mass spectrome-try detection (lower limit of quantification, 10 ng/nL). Bioequivalence was concluded if the 90% CI of the ratio of AUC(0-72) and C(max) were within the regulatory criteria of 0.80 to 1.25. The safety profile was assessed through adverse events (AEs) and analysis of laboratory and echocardiogram parameters. RESULTS: In study one, 36 male subjects were enrolled and randomized (mean [SD] age, 26.1 [6.9] years; weight, 77.6 [11.0] kg; race: white, 35 [97.2%], and Asian, 1 [2.8%]). Of those, 7 were withdrawn prior to completion (5 were lost to follow-up, 1 failed the drug screening, 1 withdrew due to AEs, and 1 was excluded due to undisclosed medical history). In study two, 40 male subjects were enrolled and randomized (mean [SD] age, 31.2 [10.3] years; weight, 76.1 [9.0] kg; race: white, 38 [95.0%], black, 1 [2.5%], and other, 1 [2.5%]). Of those, 2 were withdrawn prior to completion (1 failed the urine drug screening and 1 withdrew consent). The ratios (90% CIs) of AUC(0-72) for the 100-mg and 300-mg test formulations were 1.00 (0.98-1.02) and 1.00 (0.98-1.01), respectively. The ratios (90% CIs) of C(max) were 0.97 (0.94-1.00) and 0.98 (0.95-1.00). A total of 25 subjects experienced treatment-emergent AEs in study 1; of these, 8 events in 3 patients were considered to be possibly or probably related to study drug administration. A total of 21 subjects experienced treatment-emergent AEs in study 2; of these, 11 events in 6 subjects were considered to be possibly or probably related to study drug administration. All AEs and laboratory and ECG findings were similar between formulations. CONCLUSIONS: The test formulation of zonisamide met regulatory criteria for bioequivalence to the reference formulation in these healthy male volunteers. Both formulations were generally well tolerated at both dose levels.
RCT Entities:
BACKGROUND: To make it easier for patients who are prescribed zonisamide to administer their medicine, a rapidly disintegrating oral tablet formulation has been developed. OBJECTIVE: These 2 trials assessed the bioequiva-lence of a new orally dispersible tablet formulation of zonisamide (test) versus an immediate-release reference capsule. METHODS: Study 1 assessed the bioequivalence of a 100-mg orally dispersible tablet versus a 100-mg reference capsule. Study 2 assessed the bioequivalence of a 300-mg test tablet versus three 100-mg reference capsules. Both trials were open-label, randomized-sequence, single-dose, 2-period, 2-treatment crossover studies in consenting healthy male volunteers aged 18 to 55 years. A 4-week washout separated treatment periods. The zonisamide test tablet was placed on the tongue and, after it had dispersed in saliva, swallowed without water. Zonisamide serum concentrations were analyzed using a validated high-performance liquid chromatography assay with tandem mass spectrome-try detection (lower limit of quantification, 10 ng/nL). Bioequivalence was concluded if the 90% CI of the ratio of AUC(0-72) and C(max) were within the regulatory criteria of 0.80 to 1.25. The safety profile was assessed through adverse events (AEs) and analysis of laboratory and echocardiogram parameters. RESULTS: In study one, 36 male subjects were enrolled and randomized (mean [SD] age, 26.1 [6.9] years; weight, 77.6 [11.0] kg; race: white, 35 [97.2%], and Asian, 1 [2.8%]). Of those, 7 were withdrawn prior to completion (5 were lost to follow-up, 1 failed the drug screening, 1 withdrew due to AEs, and 1 was excluded due to undisclosed medical history). In study two, 40 male subjects were enrolled and randomized (mean [SD] age, 31.2 [10.3] years; weight, 76.1 [9.0] kg; race: white, 38 [95.0%], black, 1 [2.5%], and other, 1 [2.5%]). Of those, 2 were withdrawn prior to completion (1 failed the urine drug screening and 1 withdrew consent). The ratios (90% CIs) of AUC(0-72) for the 100-mg and 300-mg test formulations were 1.00 (0.98-1.02) and 1.00 (0.98-1.01), respectively. The ratios (90% CIs) of C(max) were 0.97 (0.94-1.00) and 0.98 (0.95-1.00). A total of 25 subjects experienced treatment-emergent AEs in study 1; of these, 8 events in 3 patients were considered to be possibly or probably related to study drug administration. A total of 21 subjects experienced treatment-emergent AEs in study 2; of these, 11 events in 6 subjects were considered to be possibly or probably related to study drug administration. All AEs and laboratory and ECG findings were similar between formulations. CONCLUSIONS: The test formulation of zonisamide met regulatory criteria for bioequivalence to the reference formulation in these healthy male volunteers. Both formulations were generally well tolerated at both dose levels.