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

Masayuki Baba,1 Hiroshi Takatsuna,2 Norimitsu Matsui,3 Shoichi Ohwada4 1Aomori Prefectural Central Hospital, Aomori, Japan; 2Medical Science Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan; 3Clinical Development Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan; 4Biostatistics and Data Management Department, Daiichi Sankyo Co., Ltd., Tokyo, JapanCorrespondence: Hiroshi TakatsunaMedical Science Department, Daiichi Sankyo Co., Ltd., Tokyo 103-8425, JapanTel [phone]Fax [phone]Email [email protected]: 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: peripheral neuropathic pain, mirogabalin, creatinine clearance, dose adjustment, safety, tolerability

Keywords

• peripheral neuropathic pain
• mirogabalin
• creatinine clearance
• dose adjustment
• safety
• tolerability