Trial Design

This was a multi-center, prospective, single-arm, open-label study, which took place in 10 centers in Japan between 1 October 2019 and 30 April 2020 (details are listed in the electronic supplementary material). The study received approval from the Clinical Research Review Committee, Itabashi Hospital, Nihon University School of Medicine (CRB No. CRB3180013), which notified all participating centers of the approval. The trial was conducted in accordance with the ethical principles, clinical research laws, and relevant notifications stipulated in the Declaration of Helsinki (as revised in 2013). This study was registered in the Japan Registry of Clinical Trials under the identifier jRCTs031190113.

After obtaining informed consent, where necessary the dose of pregabalin was gradually reduced over 1 week according to the package insert [11], to reduce the risk of withdrawal symptoms. Patients with creatinine clearance (CrCL) ≥ 60 ml/min reduced their daily pregabalin dose to ≤ 150 mg, and patients with CrCL 30 to  < 60 ml/min to ≤ 75 mg; the schedule of dose reduction was at the discretion of the attending physician. At enrollment, pregabalin was stopped completely and administration of mirogabalin was initiated. Mirogabalin was titrated according to renal function (Fig. 1). For patients with CrCL ≥ 60 ml/min, mirogabalin was administered as follows: 5 mg twice daily (BID) for 1 week, 10 mg BID for 1 week, and 15 mg BID or 10 mg BID for 2 weeks. For patients with CrCL 30 to  < 60 ml/min, mirogabalin was administered as 2.5 mg BID (1 week), 5 mg BID (1 week), and 7.5 mg BID or 5 mg BID (2 weeks). From the time of informed consent to the end of the study (or discontinuation), changes to, or additions of, new pain drugs/therapies were avoided as much as possible.

Study design. ^a ± 7 days; i.e., dose-adjustment period could begin anywhere between days 9 and 22. ^b ± 7 days; i.e., end of study occurred anywhere between days 22 and 36. BID twice daily, CrCL creatinine clearance