Effect of coadministration of metformin with mirogabalin: Results from a phase 1, randomized, open-label, drug-drug interaction study

Mirogabalin, a selective voltage-dependent calcium channel α2δ ligand under development for treatment of neuropathic pain, may be coadministered with metformin in patients with type 2 diabetes mellitus who have diabetic peripheral neuropathic pain. A randomized, open-label, single-dose, 3-treatment, 3-period crossover study evaluated the pharmacokinetics (PK) and safety of mirogabalin and metformin upon coadministration. Eligible subjects received 3 treatments separated by a 7-day washout period: 1 oral dose of mirogabalin 15 mg; 1 oral dose of metformin 850 mg; and coadministration of mirogabalin 15 mg with metformin 850 mg. PK assessments included maximum observed plasma concentration (Cmax); time of maximum plasma concentration; area under the concentration-time curve from time 0 to the last quantifiable concentration, and from 0 to infinity (AUClast and AUC0-inf, respectively). Safety assessments included adverse event (AE) monitoring and physical and clinical laboratory evaluations. 21 healthy men with a mean age of 30.4 years were enrolled and completed the study. Geometric least square means ratios (coadministration vs. alone; 90% confidence interval) for metformin Cmax, AUClast, and AUC0-inf were 1.00 (0.95 - 1.05), 1.04 (1.00 - 1.07), and 1.03 (1.00 - 1.07), respectively; ratios for mirogabalin were 0.94 (0.87 - 1.02), 0.99 (0.95 - 1.04), and 1.00 (0.96 - 1.04), respectively. Three subjects reported treatment-emergent AEs: dyspepsia, headache, and increased hepatic enzymes (resolved upon follow-up without sequelae). There were no deaths, serious AEs, or discontinuations due to AEs. Coadministration of mirogabalin and metformin is well tolerated in healthy subjects with no evidence of a drug-drug interaction. .