A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 14-Week Study of Mirogabalin in Chinese Patients with Diabetic Peripheral Neuropathic Pain

Abstract

Introduction: There is no approved effective drug for diabetic peripheral neuropathic pain (DPNP) in China. Gabapentinoids including mirogabalin have shown promise, although data in Chinese patients are scarce.

Methods: This phase 3, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of mirogabalin for treating DPNP in China. Mirogabalin was administered at 5 mg twice daily for the first week and uptitrated to 15 mg twice daily for a total duration of 14 weeks. The primary efficacy endpoint was the change from baseline in weekly average daily pain score (ADPS) at week 14; secondary endpoints included the ADPS responder rate, Short-Form McGill Pain Questionnaire visual analogue scale score, patient global impression of change (PGIC), average daily sleep interference score (ADSIS), EuroQol 5-dimensions 5-levels (EQ-5D-5L), and incidence of treatment-emergent adverse events (TEAEs).

Results: Of 393 patients (mirogabalin, n = 196; placebo n = 197), the mean age was 58.2 years (mirogabalin, 58.7 years; placebo, 57.7 years) and 54.2% were male (mirogabalin, 56.1%; placebo, 52.3%). Mirogabalin elicited a greater change from baseline in the weekly ADPS vs. placebo at week 14: least-squares mean difference (95% confidence interval) vs. placebo - 0.39 (- 0.74, - 0.04), p = 0.0301. PGIC, ADSIS, and EQ-5D-5L data reflected significantly better improvements for patients receiving mirogabalin vs. placebo. The incidence of TEAEs was 75.0% and 75.1% in the mirogabalin and placebo groups, respectively. Most TEAEs were mild or moderate, and the incidence of TEAEs leading to treatment discontinuation was 2.6% in the mirogabalin group and 1.5% in the placebo group.

Conclusions: Although the effect size of mirogabalin was reduced due to the placebo effect, mirogabalin is a safe and effective treatment option for Chinese patients with DPNP.

Trial registration: ClinicalTrials.gov identifier, NCT04094662.

Keywords: China; Diabetes complications; Mirogabalin; Neuralgia; Phase 3.

Fig. 1

Study design. Patients underwent screening at visit 1, at which demographics and baseline data were collected and physical exams were performed. Patients were also instructed on the use of electronic diaries and completed SF-MPQ, HADS, and C-SSRS. At visit 2 (observation), patient diaries were reviewed. Patients were randomly allocated to treatment groups at visit 3 and underwent minimal physical exams, laboratory tests, and completed SF-MPQ, HADS, EQ-5D-5L, C-SSRS, and MOS-Sleep evaluations. Patients attended the study site every week for visits 3–5 and every 2 weeks for visits 6–10 during the treatment period. At visit 11 (end of treatment), patients underwent full physical exams, laboratory tests, and completed SF-MPQ, PGIC, HADS, EQ-5L-5D, C-SSRS, and MOS-Sleep evaluations. Post-treatment follow-up was conducted at visit 12 and included the HADS and C-SSRS evaluations, as well as physical exams and laboratory tests. BID twice daily, C-SSRS Colombia-Suicide Severity Rating Scale, HADS Hospital Anxiety and Depression Scale, IC informed consent, MOS-Sleep Medical Outcomes Study Sleep Scale, PGIC patient global impression of change, SF-MPQ Short-Form McGill Pain Questionnaire

Fig. 2

Patient disposition. ^aIncludes discontinuations due to the COVID-19 pandemic. mITT modified intention-to-treat

Fig. 3

Time-course of least-squares mean weekly average daily pain score (modified intention-to-treat analysis set). Data were imputed using a multiple imputation method using a pattern mixture model with shifting parameters of [adverse event, lack of efficacy, any other reason] = [1.0, 1.0, 0.5] and a mixed-effects model for repeated measures. Data are least-squares mean with standard error. 0 = no pain; 10 = worst pain imaginable