{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:20:23Z","timestamp":1791829223567,"version":"4.3.4"},"reference-count":13,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>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.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the efficacy and safety of capsules containing \u03b3-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>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.<\/jats:p><\/jats:sec>Intervention<\/jats:title>In stage 1, enrolled patients (n\u2009=\u2009363) 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\u2009=\u2009362) 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.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>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<\/jats:italic> values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences.<\/jats:p><\/jats:sec>Results<\/jats:title>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 \u22122.24 (1.55) for the 40-mg\/d and \u22122.16 (1.79) for 80-mg\/d groups and \u22121.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P<\/jats:italic>\u2009&amp;lt;\u2009.001). In a safety set (n\u2009=\u2009726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>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.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT04647773<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.25614","type":"journal-article","created":{"date-parts":[[2024,8,19]],"date-time":"2024-08-19T15:02:39Z","timestamp":1724079759000},"page":"e2425614","source":"Crossref","is-referenced-by-count":26,"title":["GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain"],"prefix":"10.1001","volume":"7","author":[{"given":"Xiaohui","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Peking University First Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Peking University First Hospital, Beijing, 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of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Emergency General Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Pingxiang People\u2019s hospital, Pingxiang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Cangzhou People\u2019s Hospital, Cangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Qiqihar First Hospital, Qiqihar, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Kaifeng Hospital of Traditional Chinese Medicine, Kaifeng, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shandong Medical University Affiliated Jinan Central Hospital, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, First Affiliated Hospital of Xi\u2019an Medical College, Xian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhejiang Provincial People\u2019s Hospital, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xulei","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Shanghai Tongji Hospital, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianrong","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifeng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The Second Hospital of Jilin University, Changchun, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Yijishan Hospital of Wannan Medical College, Wuhu, 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IDF Diabetes Atlas, 10th ed. 2021. Accessed July 16, 2024. https:\/\/diabetesatlas.org\/"},{"key":"zoi240799r11","unstructured":"To Evaluate the Long-term Safety and Efficacy of HSK16149 in Chinese Patients With Peripheral Neuralgia. ClinicalTrials.gov identifier: NCT05890053. Updated May 24, 2023. 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