The Clinical Application and Progress of Mirogabalin on Neuropathic Pain as a Novel Selective Gabapentinoids

Table 5

Summary of phase II and phase III clinical trials published about mirogabalin.

No.	Author/year	Disease	Study	Drug doses	Enroll	Race	Study endpoint	Serious AEs (SAEs) in the mirogabalin groups
1	Aaron Vinik/2014	DPNP	Phase II (NCT01496365)	Mirogabalin 5, 10, 15 mg, QD, 10, 15 mg, BID; placebo; pregabalin 150 mg BID for week 5	452	White; Black/African American; others	Mirogabalin groups were well tolerated and had statistically significant reductions in ADPS versus placebo.	One case: ALT ULN, ULN, and total bilirubin ULN in 15 mg/day group.
2	Domenico Merante/2017	DPNP	Phase II (NCT01496365)	Mirogabalin 5, 10, 15, 20, 30 mg; placebo; pregabalin 300 mg/day for week 5	452	White; Black/African American; others	Mirogabalin groups were significant reductions in ADSIS, compared with placebo ().; The percentage of subjects for the PGIC was greater in the each mirogabalin groups than that in the placebo group (31.1%) ().	One case: ALT , , and total bilirubin in 15 mg/day group.
3	Masayuki Baba/2020	DPNP	Phase II (NCT01504412)	Mirogabalin 5, 10, 15 mg, BID; placebo; pregabalin 150 mg BID for week 7	450	Asian	Mirogabalin groups were a greater improvement in ADPS, compared with placebo, although having no statistically significant.; Mirogabalin 15 mg BID significantly improved the SF-MPQ sensory and visual analog scale scores and ADSIS, versus placebo ().	No mentioned.
4	Masayuki Baba/2020	DPNP	Phase III (NCT02318706)	Placebo, mirogabalin 15, 20 or 30 mg/day for up to 14 weeks, with a 1- to 2-week titration	834	Asian	LSM change from baseline in ADPS for mirogabalin 30 mg/day was statistical significance reduction compared with placebo ().; Reductions in VAS and in ADSIS were statistically significant for mirogabalin 30 mg/day versus placebo (, ), respectively.; Significantly, more patients treated with mirogabalin 30 mg/day reported a PGIC score, compared with placebo. ().	Two cases: severe dizziness or edema in 15 mg/day group.; One case: alanine transferase and hepatic enzyme increased in 15 mg/day group.
5	Masayuki Baba/2020	DPNP	Extension study followed phase III (NCT02318706)	An initial dose of 5 mg BID for initial 2 weeks, 10 mg BID for the second 2 weeks, and increased to dosage of 10 or 15 mg BID for the reminding weeks.	214	Asian	All SF-MPQ scales, including sensory score, affective score, total score, VAS, and present pain intensity, decreased from baseline to week 52.	One case: aspartate aminotransferase increased.
6	Jitsu Kato/2019	PHN	Phase III (NCT02318719)	Mirogabalin 15 mg QD, 10 mg BID, or 15 mg BID; placebo for 14 weeks	765	Asian	Mirogabalin groups were a statistically significant difference in mean change in ADPS from baseline, compared with placebo ().; LSM change from baseline to week 14 in VAS of the SF-MPQ and the ADSIS was significantly greater in all mirogabalin groups compared with placebo ().; Significantly, more patients treated with each mirogabalin reported a PGIC score, compared with placebo ().	Pneumonia, rib fracture, and femur fracture in 15 mg/day group; erectile dysfunction, fracture, and upper limb fracture in 20 mg/day group; increased blood creatine phosphokinase, memory impairment, altered state of consciousness, cerumen impaction, and electrocardiogram change in 30 mg/day group.
7	Jitsu Kato/2020	PHN	Extension study followed phase III (NCT02318719)	An initial dose of 5 mg BID for initial 2 weeks, 10 mg BID for the second 2 weeks, and increased to a flexible maintenance dosage of 10 or 15 mg BID for the reminding weeks.	239	Asian	All SF-MPQ scales, including sensory score, affective score, total score, VAS, and present pain intensity, decreased from baseline to week 52.	A case: severe AE of dizziness. Two cases: 12-lead electrocardiogram abnormalities (atrial flutter and acute myocardial infarction).
8	Masayuki Baba/2020	Renal impairment with DPNP or PHN	Phase III; NCT02607280	7.5 mg BID for moderate impairment and 7.5 mg QD for severe impairment	35	Japanese	Significantly decreased ADPS from baseline in patients with renal impairment.	No unexpected adverse.
9	Lesley M. Arnold/2019	FM	Phase III (NCT02146430); (NCT02187159); (NCT02187471); Extension study (NCT02234583)	Mirogabalin 15 mg QD; mirogabalin 15 mg BID; placebo; pregabalin 150 mg BID	3864	North America, Asia Pacific, Eastern Europe, Western Europe, and Latin America	No statistical significance for the change in ADPS at week 13 at mirogabalin groups, as well as the effect on key secondary endpoints.; Conclusions cannot be drawn regarding the long term effect of mirogabalin on pain.	No unexpected adverse.