Banner Life Sciences LLC, 3980 Premier Dr., Suite 110, High Point, NC, 27265, USA.
INDAPharma, LLC, High Point, NC, USA.
CNS Drugs. 2021 May;35(5):567-574. doi: 10.1007/s40263-021-00799-9. Epub 2021 Mar 30.
Tecfidera (dimethyl fumarate [DMF]) is an approved product for the treatment of relapsing forms of multiple sclerosis. Monomethyl fumarate (MMF) is the only active metabolite of DMF and is responsible for its therapeutic efficacy.
The objective of this study was to determine whether two Bafiertam™ capsules each containing 95 mg of MMF is bioequivalent to one Tecfidera capsule containing 240 mg of DMF, a prodrug of MMF.
This was a single-dose, open-label, randomized, two-way crossover study evaluating two treatments over two periods with a washout interval between treatments. Fifty healthy subjects were randomized to receive a single dose of the test drug MMF 190 mg as 2 × 95 mg delayed-release capsules or the reference drug DMF 240 mg as a 1 × 240-mg delayed-release capsule. Blood samples were obtained prior to dosing and at prespecified time points through 24 h post-dose to determine plasma concentrations of MMF. The pharmacokinetic parameters of MMF were calculated including maximum observed concentration, time to reach maximum observed concentration, apparent half-life of the drug in plasma, AUC which is the area under the plasma concentration-time curve (AUC) from time zero (dosing time) to the last time point, t, with measurable analyte concentration, and AUC, which is AUC plus the extrapolated AUC from time t to infinity.
The geometric least-squares mean ratios (90% confidence interval) of the test drug MMF vs the reference drug DMF were 96.80% (92.18-101.64), 96.35% (91.81-101.12), and 104.84% (95.54-115.05) for AUC, AUC, and maximum observed concentration, respectively. Two capsules of Bafiertam™ was safe and generally well tolerated. The most common adverse event for both products was flushing, 60% and 51%, for Bafiertam™ and Tecfidera, respectively.
Based on the statistical analysis results of the pharmacokinetic parameters of MMF, a single oral dose of two Bafiertam™ DR 95 mg capsules is bioequivalent to a single oral dose of one Tecfidera DR 240 mg capsule.
This study was retrospectively registered with ClinicalTrials.gov (NCT04570670) on 30 September, 2020.
特立氟胺（富马酸二甲酯[DMF]）是一种批准用于治疗多发性硬化症复发形式的产品。单甲基富马酸（MMF）是 DMF 的唯一活性代谢物，负责其治疗效果。
本研究的目的是确定两种 Bafiertam™胶囊，每粒含 95mg MMF，是否与 Tecfidera 胶囊（MMF 的前药）中的 240mg DMF 生物等效。
这是一项单剂量、开放标签、随机、两交叉研究，在两种治疗方法之间有一个洗脱期。50 名健康受试者被随机分为接受单次测试药物 MMF 190mg，即 2×95mg 延迟释放胶囊，或参考药物 DMF 240mg，即 1×240mg 延迟释放胶囊。在给药前和给药后 24 小时内的预定时间点采集血样，以确定 MMF 的血浆浓度。计算 MMF 的药代动力学参数，包括最大观察浓度、达到最大观察浓度的时间、药物在血浆中的表观半衰期、从零时（给药时间）到最后可测量分析物浓度的时间 t 的 AUC，以及 AUC 加上从时间 t 到无穷大的外推 AUC。
测试药物 MMF 与参考药物 DMF 的几何最小二乘均值比（90%置信区间）分别为 96.80%（92.18-101.64）、96.35%（91.81-101.12）和 104.84%（95.54-115.05），用于 AUC、AUC 和最大观察浓度。Bafiertam™的两种胶囊是安全的，通常耐受性良好。两种产品最常见的不良事件均为潮红，Bafiertam™和 Tecfidera 分别为 60%和 51%。
基于 MMF 药代动力学参数的统计分析结果，单次口服 Bafiertam™DR 95mg 两种胶囊与单次口服 Tecfidera DR 240mg 胶囊生物等效。
本研究于 2020 年 9 月 30 日在 ClinicalTrials.gov（NCT04570670）进行了回顾性注册。
