A recent industry perspective published in this journal describes the benefits received by drug companies from participation in the MIDD Pilot Program. Along with the primary objectives of supporting good decision‐making in drug development, there were substantial savings in time and development costs. Furthermore, many sponsors reported qualitative benefits such as new learnings and clarity on MIDD strategies and methodology that could be applied to other development programs. Based on the success of the Pilot Program, the FDA recently announced the continuation of the MIDD Paired Meeting Program as part of the Prescription Drug User Fee Act (PDUFA VII). In this report, we describe the collective experiences of industry participants in the MIDD Program to date, including all aspects of the process from meeting request submission to follow‐up actions. The purpose is to provide future participants with information to optimize the value of the MIDD Program.

This study was designed to assess the quantitative performance of endogenous drug–drug interaction (DDI) biomarkers (N1‐methylnicotinamide (1‐NMN), N1‐methyladenosine (m¹A), and creatinine) for the organic cation transporters, OCT2 and MATE1/2K in the kidney. Ten healthy volunteers received cimetidine (400 and 800 mg, single dose) or dolutegravir (50 mg, twice a day) together with metformin (500 mg). Cimetidine and dolutegravir were considered to act mainly as MATE1/2K and OCT2 inhibitors, respectively. The renal clearance (CL_r) of metformin was decreased by 15.5% and 42.5% by cimetidine 400 and 800 mg, and by 26.8% and 56.9% by dolutegravir first and fifth doses, respectively. CL_r ratio (CL_rR) of 1‐NMN were 0.93 and 0.64 for cimetidine 400 and 800 mg, and 0.87 and 0.47 for dolutegravir first and fifth doses, respectively. CL_rR of m¹A was less than that of 1‐NMN: 1.0 and 0.80 for cimetidine 400 and 800 mg, and 0.77 and 0.71 for dolutegravir first and fifth doses, respectively. CL_r of creatinine was significantly decreased only by cimetidine 800 mg. Individual CL_rR of 1‐NMN and m¹A showed a positive correlation with the corresponding CL_rR of metformin with r² of 0.58 and 0.55, respectively. When evaluated individually, m¹A showed a better correlation during cimetidine periods (r² 0.64) than 1‐NMN (r² 0.36), but vice versa during dolutegravir periods (r² 1‐NMN, 0.80; m¹A, 0.32). These results suggest that 1‐NMN and m¹A might be more promising than creatinine as endogenous biomarkers for quantitatively assessing the DDI potential of investigational drugs for OCT2 and MATE1/2K based on their CL_rR change.