■没有专门针对疼痛性小纤维神经病(SFN)的药物治疗。传送,第二阶段丰富的注册研究,评估了维索三嗪的疗效和安全性,电压和使用依赖性钠通道阻滞剂,在患有特发性或糖尿病相关疼痛SFN的参与者中。
■运输是第二阶段,多中心,安慰剂对照,双盲(DB),丰富的入学率,随机戒断研究。该研究于2018年5月17日至2021年4月12日在13个国家(欧洲和加拿大)的68个地点进行。在为期4周的开放标签期中,265名患有疼痛性SFN(大纤维神经病和小纤维神经病的混合物并非排他性)的成年人每天两次(BID)接受口服维索三嗪350mg,123名参与者(在开放标签期间平均每日疼痛[ADP]评分比基线降低≥30%)被随机分为1:1:1,接受200mgBID,350mgBID或安慰剂,为期12周的双盲(DB)期。主要终点是DB第12周时ADP相对于基线的变化。次要终点包括ADP从基线降低≥30%的参与者比例和DB第12周时患者整体疼痛印象(PGIC)应答者的比例。监测因治疗引起的不良事件(AE)。统计显著性设定为0.10(双侧)。该试验在ClinicalTrials.gov(NCT03339336)和ClinicalTrialsregister上注册。欧盟(2017-000991-27)。
■使用维索三嗪200mgBID(-0.85;SE,0.43;95%CI,-1.71至0.00;p=0.050),但不是350毫克BID(-0.17;SE,0.43;95%CI,-1.01至0.68;p=0.70)。数字上,但没有统计学意义,与安慰剂相比,更多接受维索三嗪的参与者ADP从基线降低≥30%(68.3-72.5%vs52.5%),在DB第12周,仅350mgBID组的PGIC应答者显著高于安慰剂组(48.8%vs30.0%;比值比=2.60;95%CI,0.97-6.99;p=0.058).维索三嗪组的AE大多为轻度至中度。DB200mgBID和350mgBID维索三嗪组中最常见的不良事件(≥5%的维索三嗪治疗的参与者)是跌倒,鼻咽炎,肌肉痉挛,和尿路感染.
■在我们的研究中,维索三嗪200毫克,但不是350毫克的BID,达到主要终点;在DB第12周时,更多接受维索三嗪治疗的参与者ADP比基线降低≥30%。在SFN患者中,维索三嗪(两种剂量)的耐受性良好。
■Biogen,Inc.
UNASSIGNED: No pharmacological treatments are specifically indicated for painful small fibre neuropathy (SFN). CONVEY, a phase 2 enriched-enrolment study, evaluated the efficacy and safety of vixotrigine, a voltage- and use-dependent sodium channel blocker, in participants with idiopathic or diabetes-associated painful SFN.
UNASSIGNED: CONVEY was a phase 2, multicentre, placebo-controlled, double-blind (DB), enriched-enrolment, randomised withdrawal study. The study was conducted at 68 sites in 13 countries (Europe and Canada) between May 17, 2018, and April 12, 2021. Following a 4-week open-label period in which 265 adults with painful SFN (a mixture of large and small fibre neuropathy was not exclusionary) received oral vixotrigine 350 mg twice daily (BID), 123 participants (with a ≥30% reduction from baseline in average daily pain [ADP] score during the open-label period) were randomised 1:1:1 to receive 200 mg BID, 350 mg BID or placebo for a 12-week double-blind (DB) period. Primary endpoint was change from baseline in ADP at DB Week 12. Secondary endpoints included the proportion of participants with a ≥30% reduction from baseline in ADP and the proportion of Patient Global Impression of Pain (PGIC) responders at DB Week 12. Treatment-emergent adverse events (AEs) were monitored. Statistical significance was set at 0.10 (2-sided). The trial was registered on ClinicalTrials.gov (NCT03339336) and on ClinicalTrialsregister.eu (2017-000991-27).
UNASSIGNED: A statistically significant difference from placebo in least squares mean reduction in ADP score from baseline to DB Week 12 was observed with vixotrigine 200 mg BID (-0.85; SE, 0.43; 95% CI, -1.71 to 0.00; p = 0.050) but not 350 mg BID (-0.17; SE, 0.43; 95% CI, -1.01 to 0.68; p = 0.70). Numerically, but not statistically significantly, more participants who received vixotrigine vs placebo experienced a ≥30% ADP reduction from baseline (68.3-72.5% vs 52.5%), and only the 350 mg BID group had significantly more PGIC responders vs placebo (48.8% vs 30.0%; odds ratio = 2.60; 95% CI, 0.97-6.99; p = 0.058) at DB Week 12. AEs were mostly mild to moderate in the vixotrigine groups. The most common AEs (≥5% of vixotrigine-treated participants) in the DB 200 mg BID and 350 mg BID vixotrigine groups were falls, nasopharyngitis, muscle spasm, and urinary tract infection.
UNASSIGNED: In our study, vixotrigine 200 mg BID, but not 350 mg BID, met the primary endpoint; more vixotrigine-treated participants experienced a ≥30% reduction from baseline in ADP at DB Week 12. Vixotrigine (at both dosages) was well tolerated in participants with SFN.
UNASSIGNED: Biogen, Inc.