Baba Masayuki, Kuroha Masanori, Ohwada Shoichi, Murayama Emiko, Matsui Norimitsu
Aomori Prefectural Central Hospital, Aomori, Japan.
Clinical Development Department, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Pain Ther. 2020 Jun;9(1):261-278. doi: 10.1007/s40122-020-00156-6. Epub 2020 Feb 12.
Almost one-quarter of Asian patients with diabetes experience diabetic peripheral neuropathic pain (DPNP), which may be associated with moderate or severe levels of pain, insomnia, mood disorders, and worsened quality of life. Current treatments are generally ineffective and may be poorly tolerated. We evaluated mirogabalin as a treatment for DPNP in Asian subjects.
This phase 2, randomized, double-blind, controlled study was conducted in Japan, South Korea, and Taiwan. Subjects (n = 450) with DPNP were randomized (1:1:1:1:1) to treatment with 5, 10, or 15 mg twice-daily (BID) mirogabalin, 150 mg BID pregabalin, or placebo. The primary endpoint was change from baseline in average daily pain score (ADPS) at week 7; secondary endpoints included responder rates, Short-Form McGill Pain Questionnaire (SF-MPQ), Patient Global Impression of Change (PGIC), average daily sleep-interference score (ADSIS), and incidence of treatment-emergent adverse events (TEAEs).
A greater improvement was noted for each mirogabalin treatment group for change from baseline in ADPS at week 7 compared with both placebo and with pregabalin, although these improvements were not statistically significant. The percentage of 30, 50, and 75% responders and subjects with PGIC improvements was greater in each mirogabalin group versus placebo. Mirogabalin 15 mg BID significantly improved the SF-MPQ sensory (p = 0.0313) and visual analog scale scores (p = 0.0093), and ADSIS (p = 0.0002), versus placebo. Treatment was generally well tolerated; the most frequently reported TEAEs in the mirogabalin groups were somnolence (14.7%) and dizziness (11.0%), and most AEs were mild or moderate even at the highest dose.
In Asian subjects with DPNP, mirogabalin (5, 10, and 15 mg BID) was well tolerated. Although no significant differences were observed in the primary endpoint, there was a tendency toward improvement of pain with mirogabalin treatment, and this trend was also observed in the secondary endpoints.
ClinicalTrials.gov identifier, NCT01504412.
近四分之一的亚洲糖尿病患者患有糖尿病性周围神经病变性疼痛（DPNP），这可能与中度或重度疼痛、失眠、情绪障碍以及生活质量下降有关。目前的治疗方法通常无效，且耐受性可能较差。我们评估了米罗加巴林对亚洲受试者DPNP的治疗效果。
这项2期随机双盲对照研究在日本、韩国和台湾进行。患有DPNP的受试者（n = 450）被随机分为五组（1:1:1:1:1），分别接受每日两次（BID）5毫克、10毫克或15毫克的米罗加巴林治疗、每日两次150毫克的普瑞巴林治疗或安慰剂治疗。主要终点是第7周时平均每日疼痛评分（ADPS）相对于基线的变化；次要终点包括缓解率、简短麦吉尔疼痛问卷（SF - MPQ）、患者总体印象变化（PGIC）、平均每日睡眠干扰评分（ADSIS）以及治疗中出现的不良事件（TEAE）的发生率。
与安慰剂组和普瑞巴林组相比，各米罗加巴林治疗组在第7周时ADPS相对于基线的变化有更大改善，尽管这些改善无统计学意义。各米罗加巴林组中30%、50%和75%缓解者以及PGIC有改善的受试者的百分比均高于安慰剂组。与安慰剂相比，每日两次15毫克的米罗加巴林显著改善了SF - MPQ感觉评分（p = 0.0313）、视觉模拟量表评分（p = 0.0093）以及ADSIS（p = 0.0002）。治疗总体耐受性良好；米罗加巴林组中最常报告的TEAE是嗜睡（14.7%）和头晕（11.0%），即使在最高剂量下，大多数不良事件也为轻度或中度。
在患有DPNP的亚洲受试者中，米罗加巴林（每日两次5毫克、10毫克和15毫克）耐受性良好。虽然在主要终点未观察到显著差异，但米罗加巴林治疗有使疼痛改善的趋势，并且在次要终点也观察到了这一趋势。
ClinicalTrials.gov标识符，NCT01504412。
