Mirogabalin in Japanese Patients with Renal Impairment and Pain Associated with Diabetic Peripheral Neuropathy or Post-Herpetic Neuralgia: A Phase III, Open-Label, 14-Week Study

Abstract

Purpose: Mirogabalin was recently approved in Japan for the treatment of peripheral neuropathic pain, based on data from clinical trials in diabetic peripheral neuropathic pain (DPNP) and post-herpetic neuralgia (PHN), common clinical conditions which cause intense distress for patients. We characterized the safety and tolerability of mirogabalin in Japanese patients with renal impairment.

Patients and methods: This multicenter, open-label study (ClinicalTrials.gov identifier NCT02607280) enrolled renally impaired individuals aged ≥20 years diagnosed with DPNP or PHN, and with an average daily pain score (ADPS) of ≥4 over the 7 days prior to treatment initiation. Mirogabalin dosage was titrated for 2 weeks, followed by a fixed dose for 12 weeks according to degree of renal impairment: 7.5 mg twice daily for moderate impairment and 7.5 mg once daily for severe impairment. The primary endpoint was safety and tolerability of mirogabalin, evaluated via treatment-emergent adverse events (TEAEs). Secondary efficacy endpoints included change in ADPS from baseline to Week 14.

Results: Overall, 35 patients were enrolled (30 with moderate and 5 with severe renal impairment). Most TEAEs were mild or moderate in severity; the most commonly reported were nasopharyngitis (22.9%) and somnolence (11.4%). Only 4 patients (11.4%) discontinued treatment due to TEAEs. Mirogabalin significantly decreased ADPS from baseline in patients with renal impairment; least squares mean change from baseline at Week 14 was -1.9 (95% confidence interval: -2.8, -1.0).

Conclusion: Mirogabalin was well tolerated and significantly reduced pain levels when used to treat DPNP/PHN at a fixed dose of 7.5 mg once or twice daily in patients with renal impairment.

Keywords: creatinine clearance; dose adjustment; mirogabalin; peripheral neuropathic pain; safety; tolerability.

Conflict of interest statement

All authors have received personal fees from Daiichi Sankyo Co., Ltd. HT, NM, and SO are employees of Daiichi Sankyo Co., Ltd. The authors report no other conflicts of interest in this work.

© 2020 Baba et al.

Figures

Figure 1

Patient disposition. Note:aOne event each of angina pectoris, hepatitis E, myelitis, and somnolence. Abbreviations: AE, adverse event; CLCR, creatinine clearance.

Figure 2

Study design. Notes:aAfter obtaining informed consent, patients who were treated with prohibited concomitant medications (DPNP and PHN) or prohibited concomitant therapies (PHN) underwent a washout period of ≥7 days. Abbreviations: BID, twice daily; CLCR, creatinine clearance; DPNP, diabetic peripheral neuropathic pain; PHN, post-herpetic neuralgia; QD, once daily.

Figure 3

Time course of average daily pain scoresa (efficacy analysis set). Notes:aData are shown as least squares mean ± SE. The MI method using pattern mixture model with different shifting parameters according to the reason for treatment discontinuation was applied. The MMRM with CLCR group, week and CLCR group-by-week as fixed effects and baseline ADPS as a covariate was performed to estimate the least squares means and the corresponding SE for each week. Abbreviations: ADPS, average daily pain score; CLCR, creatinine clearance; MI, multiple imputation; MMRM, mixed-effects model with repeated measures; RI, renal impairment; SE, standard error.