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Background and Objective <p>Mirogabalin besylate is a selective α2δ-1 ligand approved for diabetic peripheral neuropathic pain. This study evaluated the pharmacokinetic (PK) bioequivalence and safety of generic 5 mg and 10 mg mirogabalin formulations compared with the reference product (Tarlige<sup>®</sup>) under both fasting and fed conditions among healthy Chinese volunteers.</p> Methods <p>This pooled analysis comprised two independent, randomized, open-label, two-period crossover trials: one evaluating the 5 mg formulation (24 participants/group) and another evaluating the 10 mg formulation (36 participants/group). Liquid chromatography–tandem mass spectrometry (LC–MS/MS) assays have been validated over ranges of 1.00–200 ng/mL (5-mg study) and 0.50–500 ng/mL (10-mg study) for plasma mirogabalin quantification. Primary endpoints were peak plasma concentration (<i>C</i><sub>max</sub>), area under the plasma concentration–time curve from time zero to the last quantifiable time point (AUC<sub>0–<i>t</i></sub>), and area under the plasma concentration–time curve from time zero to infinity (AUC<sub>0–∞</sub>). Bioequivalence was determined if the 90% confidence intervals (CIs) of geometric mean ratios (GMRs) fell within the 80.00–125.00% range, evaluated via analysis of variance (ANOVA) on log-transformed parameters.</p> Results <p>For the 5 mg formulation, the fasting study demonstrated bioequivalence with a <i>C</i><sub>max</sub> GMR of 99.10% (90% CI 91.23–107.64), AUC<sub>0–<i>t</i></sub> of 99.50% (97.14–101.91), and AUC<sub>0–∞</sub> of 99.29% (96.96–101.68). Under fed conditions, <i>C</i><sub>max</sub> showed higher variability (GMR: 88.61%, 80.48–97.55), while AUC<sub>0–<i>t</i></sub> (98.55%, 96.42–100.73) and AUC<sub>0–∞</sub> (99.03%, 97.00–101.10) remained within equivalence bounds. The 10 mg formulation exhibited robust bioequivalence in both fasting and fed states: fasting <i>C</i><sub>max</sub> GMR was 97.07% (91.84–102.60), AUC<sub>0–<i>t</i></sub> 100.61% (98.52–102.74), and AUC<sub>0–∞</sub> 100.55% (98.61–102.53); fed <i>C</i><sub>max</sub> was 97.14% (89.64–105.26), AUC<sub>0–<i>t</i></sub> 101.04% (99.26–102.86), and AUC<sub>0–∞</sub> 100.53% (99.03–102.05). An exploratory analysis of the two dose levels suggested a linear PK for mirogabalin within the 5–10 mg range. The intrasubject variability was generally low (CV<sub>W</sub>%: 3.76–20.36%), with the 10 mg formulation showing numerically lower variability for <i>C</i><sub>max</sub> (13.79%) compared with the 5 mg formulation (16.39%) in the fasting state. Adverse event incidence ranged from 13.0% to 25.0% across groups, with no severe events reported.</p> Conclusions <p>Both generic formulations met bioequivalence criteria to Tarlige<sup>®</sup> across studied doses. While both formulations showed acceptable PK profiles, the 10 mg dose exhibited more consistent exposure characteristics, as evidenced by a lower within-subject variability. The PK data are consistent with linear PK for mirogabalin within the studied dose range. Comparable safety profiles support the pharmaceutical equivalence in the studied population. These findings provide critical PK evidence for China’s first generic mirogabalin products.</p> Trial Registration No. <p>(<a href="http://www.chinadrugtrials.org.cn">http://www.chinadrugtrials.org.cn</a>)<b>:</b> 5 mg: CTR20232783; 10 mg: CTR20242717</p>

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Bioequivalence and Comparative Pharmacokinetics of Two Generic Mirogabalin Besylate Tablets (5 mg and 10 mg) and Tarlige® in Healthy Chinese Volunteers: A Pooled Analysis of Two Randomized, Open-Label, Two-Period Crossover Studies

  • 期刊论文

  • 发表日期：

    2026年2月5日

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  • Fengling Wang,
  • Haitao Yu,
  • Xi Ye,
  • Liying Wei,
  • Xiaolian Xiong,
  • Lili Zhu,
  • Limin Zheng,
  • Fan Li,
  • Angeng Wang,
  • Chenhui Li,
  • Xiangyun Meng

摘要

Background and Objective

Mirogabalin besylate is a selective α2δ-1 ligand approved for diabetic peripheral neuropathic pain. This study evaluated the pharmacokinetic (PK) bioequivalence and safety of generic 5 mg and 10 mg mirogabalin formulations compared with the reference product (Tarlige®) under both fasting and fed conditions among healthy Chinese volunteers.

Methods

This pooled analysis comprised two independent, randomized, open-label, two-period crossover trials: one evaluating the 5 mg formulation (24 participants/group) and another evaluating the 10 mg formulation (36 participants/group). Liquid chromatography–tandem mass spectrometry (LC–MS/MS) assays have been validated over ranges of 1.00–200 ng/mL (5-mg study) and 0.50–500 ng/mL (10-mg study) for plasma mirogabalin quantification. Primary endpoints were peak plasma concentration (Cmax), area under the plasma concentration–time curve from time zero to the last quantifiable time point (AUC0–t), and area under the plasma concentration–time curve from time zero to infinity (AUC0–∞). Bioequivalence was determined if the 90% confidence intervals (CIs) of geometric mean ratios (GMRs) fell within the 80.00–125.00% range, evaluated via analysis of variance (ANOVA) on log-transformed parameters.

Results

For the 5 mg formulation, the fasting study demonstrated bioequivalence with a Cmax GMR of 99.10% (90% CI 91.23–107.64), AUC0–t of 99.50% (97.14–101.91), and AUC0–∞ of 99.29% (96.96–101.68). Under fed conditions, Cmax showed higher variability (GMR: 88.61%, 80.48–97.55), while AUC0–t (98.55%, 96.42–100.73) and AUC0–∞ (99.03%, 97.00–101.10) remained within equivalence bounds. The 10 mg formulation exhibited robust bioequivalence in both fasting and fed states: fasting Cmax GMR was 97.07% (91.84–102.60), AUC0–t 100.61% (98.52–102.74), and AUC0–∞ 100.55% (98.61–102.53); fed Cmax was 97.14% (89.64–105.26), AUC0–t 101.04% (99.26–102.86), and AUC0–∞ 100.53% (99.03–102.05). An exploratory analysis of the two dose levels suggested a linear PK for mirogabalin within the 5–10 mg range. The intrasubject variability was generally low (CVW%: 3.76–20.36%), with the 10 mg formulation showing numerically lower variability for Cmax (13.79%) compared with the 5 mg formulation (16.39%) in the fasting state. Adverse event incidence ranged from 13.0% to 25.0% across groups, with no severe events reported.

Conclusions

Both generic formulations met bioequivalence criteria to Tarlige® across studied doses. While both formulations showed acceptable PK profiles, the 10 mg dose exhibited more consistent exposure characteristics, as evidenced by a lower within-subject variability. The PK data are consistent with linear PK for mirogabalin within the studied dose range. Comparable safety profiles support the pharmaceutical equivalence in the studied population. These findings provide critical PK evidence for China’s first generic mirogabalin products.

Trial Registration No.

(http://www.chinadrugtrials.org.cn): 5 mg: CTR20232783; 10 mg: CTR20242717