■许多糖尿病周围神经性疼痛(DPNP)患者的缓解不足,尽管有最好的医疗方法。在中国,尚无针对DPNP患者的有效治疗方法。
■评价含γ-氨基丁酸(GABA)类似物HSK16149胶囊治疗中国DPNP患者的疗效和安全性。
■这项2至3期适应性随机临床试验是多中心的,双盲,安慰剂和普瑞巴林控制。审判于2020年12月10日开始,并于2022年7月8日结束。在第1阶段,评估各种剂量的HSK16149以确定第2阶段的安全性和有效性。第二阶段然后验证推荐剂量的有效性和安全性。
■在第1阶段,纳入患者(n=363)随机分为1:1:1:1:1:1至4次HSK16149剂量(40、80、120或160mg/d),普瑞巴林(300毫克/天),或安慰剂。在第2阶段,患者(n=362)被随机分为1:1:1,接受HSK16149,40或80mg/d,或安慰剂。最终的疗效和安全性分析汇集了接受相同治疗的患者的数据。
■第1阶段的主要疗效终点是第5周时平均每日疼痛评分(ADPS)相对于基线的变化。第2阶段的主要疗效终点是第13周的ADPS相对于基线的变化。当进行最后的统计分析时,根据各相独立数据计算出的P值,采用加权逆正态法进行统计推断。
■在完整分析集中的725名随机患者中(393名男性[54.2%];平均[SD]年龄,58.80[9.53]岁;700[96.6%]汉族),177人接受安慰剂;178,HSK16149,40毫克/天;179,HSK16149,80毫克/天;66,HSK16149,120毫克/天;63,HSK16149,160毫克/天;和62,普瑞巴林,300mg/d。共有644名患者(88.8%)完成了研究。在第2阶段,建议使用40和80mg/d剂量的HSK16149。在第13周,40mg/d组的ADPS平均(SD)相对于基线的变化为-2.24(1.55),80mg/d组为-2.16(1.79),安慰剂组为-1.23(1.68),显示两种HSK16149剂量与安慰剂的统计学意义(两者P<.001)。在安全集中(n=726),545例患者(75.1%)出现不良事件,一般为轻度至中度,最常见的是头晕和嗜睡。
■建议在中国治疗DPNP患者的HSK16149剂量为40和80mg/d。HSK16149胶囊在缓解DPNP方面的疗效均优于安慰剂组,并表现出良好的耐受性。
■ClinicalTrials.gov标识符:NCT04647773。
UNASSIGNED: Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China.
UNASSIGNED: To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP.
UNASSIGNED: This phase 2 to 3 adaptive randomized clinical
trial was multicenter, double blind, and placebo and pregabalin controlled. The
trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose.
UNASSIGNED: In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment.
UNASSIGNED: The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences.
UNASSIGNED: Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the
study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was -2.24 (1.55) for the 40-mg/d and -2.16 (1.79) for 80-mg/d groups and -1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common.
UNASSIGNED: Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT04647773.