Background: Oral co-administration of encequidar (a selective, minimally absorbed oral P-gp inhibitor) 12.9 mg with paclitaxel (a P-gp substrate) 205 mg/m² for 3 consecutive days per week can achieve comparable AUC exposure to that of IV paclitaxel 80mg/m² with a significantly lowered C_max and has been demonstrated its improved tumor response with reduced neuropathy compared to IV paclitaxel 175 mg/m² Q3W for the treatment of patients with metastatic breast cancer. Because of its pharmacology as an inhibitor of P-gp, encequidar may increase the bioavailability of orally administered drugs that are substrates of P-gp, such as dabigatran etexilate. Methods: To determine the effect of a therapeutic dose and regimen (3 once-daily 12.9 mg doses) of encequidar on the single dose PK of dabigatran etexilate, an open-label, fixed-sequence study was performed in 20 healthy male subjects. Participants received a single oral dose of dabigatran etexilate 75 mg on Day 1 of Treatment Period 1 (reference) and, after a washout period of at least 7 days, on Days 3, 17 and 31 of Treatment Period 2, after receiving once-daily oral doses 12.9 mg encequidar on Days 1 to 3 of Period 2. The PK sampling for determination of plasma concentrations of total and unconjugated dabigatran lasted up to 48 hours postdose of each dabigatran etexilate dosr. Results: Mean AUC and C_max values for dabigatran were both increased ̃ 95% without changing t_½ when dabigatran etexilate was administered 1 hour post the 3^rd dose of 12.9 mg encequidar compared to when dabigatran etexilate was administered alone. When dabigatran etexilate was administered 2 weeks after encequidar administration, no apparent differences in dabigatran AUC or C_max were detected compared to those of dabigatran etexilate alone. When administered 4 weeks after discontinuation of encequidar, dabigatran AUC and C_max were both slightly lower than Reference dabigatran etexilate (̃ 25% lower for AUC and 34% lower for C_max). Both unconjugated and total dabigatran PK data were analyzed and shown to be similar. Encequidar and dabigatran etexilate were well tolerated and had acceptable safety findings in this healthy subject population. Conclusions: Concomitant dosing of encequidar with dabigatran etexilate resulted in < 2-fold increase in exposure to dabigatran, which had abated by the time of the first re-test, 14 days after the last dose of encequidar. The observed changes do not warrant dose adjustment of dabigatran etexilate when administered with encequidar. Clinical trial information: ACTRN12618000791235.