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Long-term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain.

ABSTRACT: AIMS/INTRODUCTION:Diabetic peripheral neuropathic pain (DPNP) affects the functionality, mood and sleep patterns of patients with diabetes. Mirogabalin, an ?2 ? ligand with a slower dissociation for ?2 ?-1 versus ?2 ?-2 subunits, showed efficacy and safety in a randomized, double-blind, placebo-controlled, 14-week study in Asian patients with DPNP. This open-label extension study evaluated the long-term safety and efficacy of mirogabalin in Asian patients with DPNP. MATERIAL AND METHODS:This 52-week open-label extension study was carried out in Japan, Korea and Taiwan in patients with DPNP. Patients received mirogabalin, initiated at 5 mg twice daily and increased to a flexible maintenance dosage of 10 or 15 mg twice daily. Adverse events were monitored throughout the study. Patients provided a self-assessment of pain using the Short-Form McGill Pain Questionnaire. RESULTS:Of the 214 patients who entered the study, 172 (80.4%) completed the extension study. Of 172 patients who completed the study, 149 received the highest dosage of mirogabalin (15 mg twice daily). The most common treatment-emergent adverse events were nasopharyngitis, diabetic retinopathy, peripheral edema, somnolence, diarrhea, increased weight and dizziness. Most treatment-emergent adverse events were mild or moderate in severity. The incidence of treatment-emergent adverse events leading to treatment discontinuation was 13.1%. The visual analog scale and all other Short-Form McGill Pain Questionnaire subscales (sensory score, affective score, total score and present pain intensity) generally decreased over time from baseline until week 52. CONCLUSIONS:This extension study showed the safety and efficacy of a long-term flexible dosing regimen of mirogabalin 10 or 15 mg twice daily in patients with DPNP.

SUBMITTER: Baba M

PROVIDER: S-EPMC7232295 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Long-term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain.

Baba Masayuki M Matsui Norimitsu N Kuroha Masanori M Wasaki Yosuke Y Ohwada Shoichi S

Journal of diabetes investigation 20191225 3

<h4>Aims/introduction</h4>Diabetic peripheral neuropathic pain (DPNP) affects the functionality, mood and sleep patterns of patients with diabetes. Mirogabalin, an α<sub>2</sub> δ ligand with a slower dissociation for α<sub>2</sub> δ-1 versus α<sub>2</sub> δ-2 subunits, showed efficacy and safety in a randomized, double-blind, placebo-controlled, 14-week study in Asian patients with DPNP. This open-label extension study evaluated the long-term safety and efficacy of mirogabalin in Asian patients ...[more]

PMID: 31722446

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Project description:IntroductionAlmost 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.MethodsThis 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).ResultsA 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.ConclusionsIn 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.Trial registrationClinicalTrials.gov identifier, NCT01504412.

Project description:IntroductionIn Japan, conservative therapy for patients with lumbar spinal stenosis (LSS) includes non-steroidal anti-inflammatory drugs (NSAIDs), prostaglandin E1, tramadol, physical/exercise therapy, and nerve blocks. Mirogabalin, a selective oral α2δ ligand, is approved for treating peripheral neuropathic pain, though data regarding visual analog scores (VAS) for pain in patients with LSS are limited. We investigated the efficacy and safety of mirogabalin as an add-on treatment in patients with LSS taking NSAIDs compared with patients taking NSAIDs only.MethodsThis multicenter, randomized, open-label study (MiroTAS) was conducted at 32 centers in Japan between June 2020 and October 2021. Patients were randomly assigned to mirogabalin and NSAIDs or NSAIDs alone in a 1:1 ratio. NSAIDs were administered according to their Japanese package inserts; mirogabalin was administered based on renal function [creatinine clearance (CrCL) ≥ 60 mL/min, 5 mg twice daily (BID) in Weeks 1-2, 10 mg BID in Weeks 3-4, and 15 or 10 mg BID after Week 5; CrCL 30 to < 60 mL/min, 2.5 mg BID Weeks 1-2, 5 mg BID Weeks 3-4, and 7.5 or 5 mg BID after Week 5]. The primary endpoint was the change in VAS score for leg pain from baseline to Week 12. Secondary endpoints were quality of life, evaluated using the EuroQol five-dimensional descriptive system (EQ-5D-5L) (at baseline and Week 12) and Patient Global Impression of Change (PGIC) (at Week 12), and safety. Change in VAS score at Week 12 was calculated using a linear mixed model for repeated measures. The safety endpoints were treatment-emergent adverse events (TEAEs) and adverse drug reactions.ResultsIn total, 220 patients who met the eligibility criteria were enrolled. In the mirogabalin and NSAIDs and NSAIDs groups, mean ages (67.8 vs. 70.9 years), proportions of female patients (54.5% vs. 49.0%), mean body weights (63.9 vs. 62.0 kg), mean CrCL values (81.5 vs. 70.7 mL/min), proportions of patients with CrCL 30 to < 60 mL/min (27.3% vs. 33.7%), mean VAS scores (63.8 vs. 62.8 mm), and proportions of patients with VAS score ≥ 60 (53.6% vs. 52.9%) at enrollment were similar. The median durations of LSS were 9.0 and 11.0 months and the spine pain DETECT questionnaire (SPDQ) scores were 6.8 and 7.8, respectively. The least square (LS) mean change in VAS score from baseline to Week 12 was - 24.1 mm in the mirogabalin and NSAIDs group and - 14.2 mm in the NSAIDs group (both P < 0.0001 vs. baseline). The difference in LS mean was - 9.9 [95% confidence interval (CI), - 18.0, - 1.8] (P = 0.0174). The improvement in EQ-5D-5L score at Week 12 was significantly greater in the mirogabalin and NSAIDs group versus the NSAIDs group [mean difference, 0.0529 (95% CI, 0.0036, 0.1022), P = 0.0357]. At Week 12, the proportions of patients with PGIC scores ≤ 3 and ≤ 2 were higher in the mirogabalin and NSAIDs group vs. the NSAIDs group (76.2% vs. 50.0%, P = 0.0006, and 47.6% vs. 32.4%, P = 0.0523). In the mirogabalin and NSAIDs group, the incidences of TEAEs and adverse drug reactions were 60.9% and 57.3%, respectively, and the most common TEAEs were somnolence (30.0%) and dizziness (25.5%).ConclusionsThe addition of mirogabalin to NSAIDs improved VAS, EQ-5D-5L, and PGIC. The main TEAEs were somnolence and dizziness. The addition of mirogabalin to NSAIDs improved peripheral neuropathic pain associated with LSS and raised no new safety concerns.Trial registrationJapan Registry of Clinical Trials (jRCTs021200007).

Project description:AimsDiabetic peripheral neuropathy affects up to 60% of individuals and often leads to foot ulceration and eventual amputation. When oral therapy has failed to achieve pain relief, the first line local treatment is the 5% lidocaine-medicated plaster which provides local relief. Capsaicin 8% patch is considered a promising topical treatment for diabetic peripheral neuropathy. The present study investigated the efficacy, safety and tolerability of capsaicin 8% patch vs 5% lidocaine patch treatments over 24 weeks in South Asian male diabetic patients with established peripheral diabetic neuropathy.MethodsAnalgesic effectiveness was assessed by observing any change in the Numeric Pain Rating Scale (NPRS) score, Brief Pain Inventory (BPI) for painful diabetic peripheral neuropathy (BPI-DPN question 4) and Patient Global Impression of Change (PGIC). All patients received 4% lidocaine gel/cream for 60 min prior to patch application. The trial was probably underpowered, taking into account the smaller than expected number of participants from the calculated 350 sample size required for the whole study. Two hundred ninety-one individuals were divided into three groups based on treatment regimen; Group LL (Lidocaine + Lidocaine), Group LP (Lidocaine + Placebo), Group LC (Lidocaine + Capsaicin). The treatment procedure was conducted once initially and then repeated once at 12 weeks. The patients were followed up on alternate weeks till 24 weeks after the initial treatment.ResultsGroup LC experienced a more significant reduction in the average pain intensity (p < 0.05) during the last twenty-four hours. Group LC showed more significant reduction of pain compared to control (p < 0.01), a baseline score of 5.4 ± 1.2 dropped to 3.2 ± 1.5 by week 24 of treatment. The change in mean daily pain intensity was - 2.2 ± 1.5 [95% CI: -2.45, -1.5]. Group LL and LC experienced a significant overall improvement (slightly, much or very much) in the health status during the study. After the second week of the treatment, patient satisfaction scores were 2.1 ± 1.1 in Group LL which increased to 3.2 ± 1.2 by week 24 of treatment. The capsaicin 8% patch appears to be reasonably well tolerated since there were no discontinuations because of serious drug-related treatment emergent adverse event (TEAEs).ConclusionsThe aim of the present study was to assess the efficacy, safety and tolerability of the 8% capsaicin patch in patients with established painful diabetic neuropathy. There was a sustained treatment response to the initial and repeat treatment of the capsaicin 8% patch over the 24 weeks. The study population was very specific so further studies are required to investigate the generalizability of the results for patients experiencing painful diabetic neuropathy. The patch could be considered as an effective long-term treatment option in individuals with painful diabetic neuropathy, particularly those experiencing inadequate pain relief or side effects from systemic therapies.

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Long-term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain.

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Long-term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain.

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