Results of Mirogabalin Treatment for Diabetic Peripheral Neuropathic Pain in Asian Subjects: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Study

Baba, Masayuki; Kuroha, Masanori; Ohwada, Shoichi; Murayama, Emiko; Matsui, Norimitsu

doi:10.1007/s40122-020-00156-6

Cited by 15 publications

(20 citation statements)

References 32 publications

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“…Thrombospondins are matrix proteins involved in synaptogenesis [ 45 ], bind to α2δ-1, are upregulated after peripheral nerve injury, and disrupt intracellular Ca2 + signaling due to the interaction with this auxiliary subunit of the calcium channel [ 46 ]. A better understanding of these phenomena is of the utmost importance to clarify the mechanism of action of α2δ-1 ligands such as gabapentin, pregabalin, and the newest mirogabalin [ 47 , 48 ], which is reportedly endowed with neuropsychiatric activities during chronic pain states [ 49 , 50 , 51 ], clinical conditions in which, for instance, these drugs are often inappropriately used in non-communicative patients [ 52 , 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

Scuteri

Rombolà

Natoli

et al. 2021

Life

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Background: DYT1 dystonia is the most common form of early-onset inherited dystonia, which is caused by mutation of torsin A (TA) belonging to the “ATPases associated with a variety of cellular activities” (AAA + ATPase). Dystonia is often accompanied by pain, and neuropathic pain can be associated to peripherally induced movement disorder and dystonia. However, no evidence exists on the effect of gabapentin in mice subjected to neuropathic pain model overexpressing human normal or mutated TA. Methods: Mice subjected to L5 spinal nerve ligation (SNL) develop mechanical allodynia and upregulation of the α2δ-1 L-type calcium channel subunit, forming a validated experimental model of neuropathic pain. Under these experimental conditions, TA is expressed in dorsal horn neurons and astrocytes and colocalizes with α2δ-1. Similar to this subunit, TA is overexpressed in dorsal horn 7 days after SNL. This model has been used to investigate (1) basal mechanical sensitivity; (2) neuropathic pain phases; and (3) the effect of gabapentin, an α2δ-1 ligand used against neuropathic pain, in non-transgenic (NT) C57BL/6 mice and in mice overexpressing human wild-type (hWT) or mutant (hMT) TA. Results: In comparison to non-transgenic mice, the threshold for mechanical sensitivity in hWT or hMT does not differ (Kruskal–Wallis test = 1.478; p = 0.4777, although, in the latter animals, neuropathic pain recovery phase is delayed. Interestingly, gabapentin (100 mg/Kg) reduces allodynia at its peak (occurring between post-operative day 7 and day 10) but not in the phase of recovery. Conclusions: These data lend support to the investigation on the role of TA in the molecular machinery engaged during neuropathic pain.

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Section: Discussionmentioning

confidence: 99%

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

Scuteri

Rombolà

Natoli

et al. 2021

Life

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“…18 Three randomised, double-blind, controlled studies were conducted to gauge the efficacy and tolerability of mirogabalin in DPNP patients. 16,19,20 Overall, these studies showed promising results that need to be confirmed in further trials.…”

mentioning

confidence: 71%

Efficacy and safety of mirogabalin treatment in patients with diabetic peripheral neuropathic pain: A systematic review and meta‐analysis of randomised controlled trials

Alyoubi

Alshareef

Aldughaither

et al. 2020

Int. J. Clin. Pract.

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Aim:We aimed to perform a systematic review and meta-analysis to examine the efficacy and safety of mirogabalin in patients with diabetic peripheral neuropathic pain (DPNP). Methods:We searched four databases from inception to 1st July 2020. We included all randomised controlled trials (RCTs) which assessed the effectiveness and safety of mirogabalin in patients with DPNP. We evaluated the quality of the included RCTs using the Cochrane risk of bias assessment tool. We pooled dichotomous outcomes as risk ratios and continuous outcomes as mean differences with 95% confidence intervals, both under the random-or fixed-effects model.Results: Three RCTs matched our inclusion criteria with a total of 1732 patients with DPNP: 1057, 534 and 141 patients received mirogabalin, placebo and pregabalin, respectively. The quality of included RCTs was marked as moderate-to-high.Mirogabalin treatment was significantly associated with a significant reduction in the average daily pain score (ADPS) compared with placebo over 7 weeks. Compared with pregabalin, mirogabalin was significantly associated with more decrease in ADPS only after 3, 4 and 5 weeks. The proportion of patients with ≥30% and ≥50% reduction in the ADPS was significantly higher in the mirogabalin vs placebo and pregabalin groups. Compared with placebo, mirogabalin was significantly associated with more adverse events of dizziness, increased weight, peripheral oedema and somnolence.The safety profile was comparable between mirogabalin and pregabalin. Conclusions:Our systematic review and meta-analysis revealed that in patients with DPNP, mirogabalin treatment was superior to placebo and pregabalin in decreasing the ADPS over time. Besides, mirogabalin was largely safe and associated with some adverse events that could be managed conservatively. | INTRODUC TI ONDiabetic peripheral neuropathic pain (DPNP) is a frequent aftermath of diabetes mellitus. It is estimated to affect nearly one-third of patients with diabetic peripheral neuropathy. 1,2 Patients with DPNP experience various morbidities, including decreased work productivity, sleep disturbance, anxiety and depression. Eventually, these morbidities unfavourably influence the quality of well-being How to cite this article: Alyoubi RA, Alshareef AA, Aldughaither SM, et al. Efficacy and safety of mirogabalin treatment in patients with diabetic peripheral neuropathic pain: A systematic review and meta-analysis of randomised controlled trials.

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“…A similarlydesigned phase 2 study showed a decreased average daily pain score and sleep interference score [31]. In another phase 2 study, mirogabalin (5,10,15,20, and 30 mg twice a day) decreased the average daily pain score, average daily sleep-interference score, and ADRs [32]. In addition, mirogabalin 10 or 15 mg twice a day showed long-term (52 wk) safety and efficacy in patients with DPNP [33].…”

Section: (3) Patients With Dpnpmentioning

confidence: 95%

“…The initial dose for adults without renal dysfunction is recommended starting from 5 mg, given orally twice a day. The dose is gradually increased by 5 mg, at an interval of at least a week, to 15 mg at the 3rd week [2,3,[25][26][27][28][29][30][31][32][33].…”

Section: Clinical Application Of Mirogabalin 1) Pharmacokineticsmentioning

confidence: 99%

Mirogabalin: could it be the next generation gabapentin or pregabalin?

et al. 2021

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Results of Mirogabalin Treatment for Diabetic Peripheral Neuropathic Pain in Asian Subjects: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Study

Cited by 15 publications

References 32 publications

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A

Efficacy and safety of mirogabalin treatment in patients with diabetic peripheral neuropathic pain: A systematic review and meta‐analysis of randomised controlled trials

Mirogabalin: could it be the next generation gabapentin or pregabalin?

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