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Efficacy and Safety for Mirogabalin Treatment as Add-On to NSAIDs with Neuropathic Pain patients caused by Lumbar Disc Herniation : An Exploratory Study

Miro-Hers

182

In the modified intention-to-treat (mITT) analysis, the mean age was 48.1 +- 15.3 years in the group receiving Mirogabalin treatment as add-on to NSAIDs(the combination therapy group) (n = 90), and 46.8 +- 16.4 years in the group receiving NSAIDs alone (the monotherapy group) (n = 89).The sex distribution was 53 males (58.9%) and 37 females (41.1%) in the combination therapy group, and 58 males (65.2%) and 31 females (34.8%) in the monotherapy group.

Participant enrollment was started in March 2023 and completed in July 2024. The final observation of study partcipants was completed in September 2024. A total of 182 participants who provided informed consent were enrolled and randomized equally into the combination therapy group and the monotherapy group, with 91 participants in each group. Among them, one patient in the combination therapy group and two participants in the monotherapy group were excluded from the safety analysis population. Consequently, the safety analysis population consisted of 90 participants in the combination therapy group and 89 in the monotherapy group. During the study, 13 participants in the combination therapy group and 16 in the monotherapy group discontinued the study.

The incidence of treatment-emergent adverse events (TEAE) was 54.4% in the combination therapy group and 10.1% in the monotherapy group. The incidence of treatment-emergent adverse drug reactions (TEADR) was 48.9% in the combination therapy group and 6.7% in the monotherapy group. No serious TEAE or TEADR, nor any TEAE of severe intensity, were observed in either group. The incidence of TEAE and TEADR leading to treatment discontinuation was 2.2% in both groups, indicating similar outcomes. Most TEAE were of mild intensity; the incidence of moderate TEAE was 8.9% in the combination therapy group. TEAE with an incidence of 5% or more in the combination therapy group were somnolence (31.1%) and dizziness (18.9%), in descending order. No TEAE with an incidence of 5% or more were observed in the monotherapy group. No previously unreported adverse events or side effects were observed in either group throughout the study period.

Primary Outcome The estimated change (95% confidence interval [CI]) from baseline to week 8 in lower limb pain as measured by the numerical rating scale (NRS) was -2.2 (-2.8, -1.7, P < 0.0001) in the monotherapy group and -3.8 (-4.4, -3.3, P < 0.0001) in the combination therapy group, indicating significant improvement in both groups. The between-group difference in change from baseline to week 8 (combination therapy group minus monotherapy group) was -1.6 (-2.4, -0.8, P = 0.0001), demonstrating a significantly greater improvement in lower limb pain in the combination therapy group compared with the monotherapy group. Secondary Outcomes 1)Change in Sleep Disturbance NRS (Week 1, 2, 4, 8) The estimated changes (95% confidence intervals [CI]) from baseline in the sleep disturbance NRS at Weeks 1, 2, 4, and 8 were -1.4 (-1.8, -1.0), -1.8 (-2.2, -1.4), -2.1 (-2.5, -1.8), and -2.5 (-2.9, -2.1), respectively, in the combination therapy group, and -0.8 (-1.2, -0.4), -0.9 (-1.3, -0.5), -1.3 (-1.6, -0.9), and -1.2 (-1.6, to -0.8), respectively, in the monotherapy group. 2)Change in Low Back Pain NRS (Week 1, 2, 4, 8) The estimated changes (95% confidence intervals [CI]) from baseline in the low back pain NRS at Weeks 1, 2, 4, and 8 were -1.4 (-1.8, -1.0), -1.5 (-2.0, -1.1), -1.8 (-2.3, -1.4), and -2.5 (-3.0, -2.0), respectively, in the combination therapy group, and -0.5 (-0.9, -0.1), -0.5 (-0.9, -0.1), -1.1 (-1.5, -0.6), and -1.4 (-1.9, -0.9), respectively, in the monotherapy group. 3)JOABPEQ (Japanese Orthopaedic Association Back Pain Evaluation Questionnaire) Score Changes (Week 2, 8) - Pain-related disorder The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were 29.1 (23.1, 35.1) and 40.4 (33.6, 47.3), respectively, in the combination therapy group, and 16.5 (10.6, 22.4) and 26.1 (19.2, 33.1), respectively, in the monotherapy group. - Lumbar function The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were 18.7 (14.7, 22.7) and 25.9 (21.6, 30.2), respectively, in the combination therapy group, and 12.5 (8.6, 16.4) and 21.6 (17.2, 26.0), respectively, in the monotherapy group. - Walking ability The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were 14.8 (11.0, 18.6) and 26.8 (21.9, 31.7), respectively, in the combination therapy group, and 8.0 (4.3, 11.8) and 16.3 (11.3, 21.2), respectively, in the monotherapy group. - Social life function The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were 17.0 (13.4, 20.5) and 28.2 (24.1, 32.4), respectively, in the combination therapy group, and 7.8 (4.4, 11.3) and 17.9 (13.7, 22.1), respectively, in the monotherapy group. - Mental health The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were 10.6 (8.1, 13.1) and 15.9 (12.9, 18.9), respectively, in the combination therapy group, and 5.7 (3.2, 8.1) and 10.2 (7.2, 13.2), respectively, in the monotherapy group. - VAS for Low Back Pain The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were -1.8 (-2.3, -1.4) and -2.5 (-3.0, -2.0), respectively, in the combination therapy group, and -0.6 (-1.1, -0.2) and -1.7 (-2.2, -1.2), respectively, in the monotherapy group. - VAS for buttock and lower Limb Pain The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were -2.5 (-3.0, -2.0) and -4.0 (-4.5, -3.4), respectively, in the combination therapy group, and -1.2 (-1.7, -0.7) and -2.6 (-3.2, -2.1), respectively, in the monotherapy group. - VAS for buttock and lower limb Numbness The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were -1.9 (-2.4, -1.5) and -3.2 (-3.8, -2.6), respectively, in the combination therapy group, and -1.0 (-1.5, -0.5) and -1.7 (-2.3, -1.1), respectively, in the monotherapy group. 4) Change in EQ-5D-5L Index Score and Health Status VAS (Week 2, 8) - EQ-5D-5L index score The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 in the EQ-5D-5L index score were 0.1138 (0.0885, 0.1391) and 0.1816 (0.1524, 0.2109), respectively, in the combination therapy group, and 0.0590 (0.0340, 0.0840) and 0.1163 (0.0866, 0.1461), respectively, in the monotherapy group. - Health Status VAS The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were 9.5 (5.9, 13.1) and 14.6 (10.1, 19.2), respectively, in the combination therapy group, and 4.6 (1.0, 8.2) and 7.0 (2.4, 11.6), respectively, in the monotherapy group. 5) Change in Neuropathic Pain Symptom Inventory (NPSI) Total Score (Week 2, 8) The estimated changes (95% confidence intervals [CI]) from baseline at weeks 2 and 8 were -12.2 (-15.1, -9.3) and -20.8 (-24.3, -17.4), respectively, in the combination therapy group, and -5.8 (-8.6, -2.9) and -12.5 (-16.0, -9.0), respectively, in the monotherapy group. 6) Patient Global Impression of Change (PGIC) at Week 8 At week 8, the PGIC categories with a proportion of 10% or more in the combination therapy group, in descending order, were: "2. Much improved" in 33 participants (44.0%) "1. Very much improved" in 18 participants (24.0%) "3. Minimally improved" in 16 participants (21.3%) In the monotherapy group: "2. Much improved" in 26 participants (36.1%) "3. Minimally improved" in 17 participants (23.6%) "4. No change" in 14 participants (19.4%) "1. Very much improved" in 9 participants (12.5%) 7) Time to 30 Percent Improvement in Lower Limb Pain NRS A total of 83 participants (92.2%) in the combination therapy group and 75 participants (84.3%) in the monotherapy group achieved a 30% or greater improvement in lower limb pain NRS from baseline. The median time (95% CI) to achieve this improvement was 5.0 days (4.0, 10.0) in the combination therapy group and 7.0 days (5.0, 11.0) in the monotherapy group. 8) Area Under the Curve (AUC) for Lower Limb Pain NRS The mean +- standard deviation of the AUC for lower limb pain NRS was 189.18 +- 103.21 in the combination therapy group and 234.27 +- 109.25 in the monotherapy group. The estimated between-group difference (combination therapy group minus monotherapy group) in mean AUC (95% CI) was -45.08 (-86.42, -3.74), with a P = 0.0329. 9)Responder Rate and Participant-Reported Treatment Satisfaction Based on Lower Limb Pain VAS At week 8, the proportion of participants achieving a 30% or greater reduction in lower limb pain VAS from baseline was 78.7% (59 participants) in the combination therapy group and 62.5% (45 participants) in the monotherapy group. The proportion of responders was significantly higher in the combination therapy group compared with the monotherapy group (P = 0.0455). For a 50% or greater reduction, the responder rate was 72.0% (54 participants) in the combination therapy group and 45.8% (33 participants) in the monotherapy group.

This study compared the efficacy and safety of NSAID monotherapy and combination therapy with NSAIDs and Mirogabalin in patients with lumbar disc herniation. The combination group showed greater improvements in pain, JOABPEQ, EQ-5D-5L, and NPSI scores. Although TEAEs and TEADRs were more frequent in the combination group, all were known and mild to moderate. These results suggest that the combination therapy may be a promising option for neuropathic pain.

Jan. 31, 2026

Oct. 17, 2025

https://link.springer.com/article/10.1007/s40122-025-00776-w

No

No

https://jrct.mhlw.go.jp/latest-detail/jRCTs061220102

Suzuki Hidenori

Yamaguchi University Hospital

1-1-1 Minamikogushi, Ube-shi, Yamaguchi

hsuzuki@yamaguchi-u.ac.jp

Suzuki Hidenori

Yamaguchi University Hospital

1-1-1 Minamikogushi, Ube-shi, Yamaguchi

+81-836-22-2111

hsuzuki@yamaguchi-u.ac.jp

Complete

Mar. 01, 2023

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1. Patients diagnosed with lumbar disc herniation by MRI imaging findings by the time of enrollment (Visit 1)
2. Patients with lower limb pain (including buttocks pain) with NRS of 4 or more due to neuropathic pain associated with lumbar disc herniation at the time of enrollment (Visit 1)
3.Patients on whom over 1 week have passed since the onset of lumbar disc herniation and are taking NSAIDs at the time of enrollment (Visit 1)
4.Patients aged 18 years or older at the time of obtaining informed consent
5.Patients who can correctly evaluate lower limb pain by distinguishing between low back pain and lower limb pain
6.Patients who can understand the procedure of this study, answer questions in Japanese appropriately in writing and by electromagnetic means (ePRO) without assistance, and give their own written consent on their own free will to participate in this study by writing or electromagnetic means (eConsent)

1.Patients with a period of 3 months or more from the onset of lower limb pain to the time of enrollment (Visit 1)
2.Patients with muscle weakness (Manual Muscle Testing; MMT<=3)*
*: tibialis anterior muscle (L4), extensor hallucis longus muscle (L5), gastrocnemius muscle (S1)
3.Patients with bladder and rectal disorders and scheduled for surgery during this study participation period
4.Patients with lower limb pain caused by disease other than lumbar disc herniation and considered difficult to be evaluated
5.Patients with severe pain caused by disease other than lumbar disc herniation and considered difficult to be evaluated
6.Patients scheduled for surgery that will affect the efficacy evaluation of lower limb pain caused by lumbar disc herniation
7.Patients with a history of lumbar spine surgery
8.Patients with creatinine clearance (CLcr) less than 30 mL/min
9.Patients with serious hepatic, renal, or cardiac disease
10.Patients who have taken prohibited concomitant medications within 7 days prior to enrollment (Visit 1)
11.Patients who have received prohibited concomitantly therapy within 7 days prior to enrollment (Visit 1)
12.Patients who have taken mirogabalin for lumbar disc herniation currently occurred
13.Patients taking mirogabalin for diseases other than lumbar disc herniation
14.Patients with a history of hypersensitivity to the ingredients of mirogabalin
15.Patients who are pregnant or possibly pregnant at the time of obtaining informed consent, patients who are breastfeeding at the time of obtaining informed consent, and patients who are planning to become pregnant within 6 months after obtaining informed consent
16.Patients participating in or scheduled to participate in other intervention studies at the time of enrollment
17.Other patients judged by the principal investigator or subinvestigator to be unsuitable for participation in this study

Both

Neuropathic pain caused by lumbar disc herniation

Comparing a lumbar disc herniation patient group taking mirogabalin add-on therapy to NSAIDs with a group taking NSAIDs monotherapy.

Change in lower limb pain NRS (Numerical Rating Scale; 11-point scale from 0 to 10, where 0 is no pain and 10 is the worst imaginable pain) from baseline to 1, 2, 4, and 8 weeks

1. Change in sleep disturbance NRS from baseline to 1, 2, 4, and 8 weeks
2. Change in low back pain NRS from baseline to 1, 2, 4, and 8 weeks
3. Change in Japanese Orthopaedic Association JOABPEQ score (lower limb motor function, QOL) from baseline to 2 and 8 weeks
4. Time course of EQ-5D-5L score and health condition VAS at each point of from baseline to 2 and 8 weeks
5. Time course of Neuropathic Pain Symptom Inventory (NPSI) score at each point of form baseline to 2 and 8 weeks
6. Patient Global Impression of Change (PGIC) at 8 weeks (assessed by 7-point scale; score 1 indicates "very much improved" and 7 indicates "very much worsened")
7. Time to 30% improvement in lower limb pain NRS from baseline
8. Area Under the Curve (AUC) of lower limb pain NRS
9. 30% responder rate and 50% responder rate at week 8 for lower limb pain VAS from baseline

+81-836-22-2428

Jan. 11, 2023

none