A phase 1 study of intravenously administered TR-701 FA in subjects with advanced renal impairment

Introduction

The objective of the study was to characterize the safety of tedizolid phosphate (TR-701 FA) and the pharmacokinetics of tedizolid (TR-700), its microbiologically active moiety, in subjects with advanced renal impairment (eGFR <30 ml/minute/1.73 m², not on dialysis) compared with matched subjects with normal renal function (eGFR ≥80.0 ml/minute/1.73 m²).

Methods

Eight subjects with advanced renal impairment and eight matched controls (by age, gender, and body mass index) received a single intravenous infusion of 200 mg TR-701 FA. Serial plasma PK samples were collected from pre-dose through 72 hours post-dose. Plasma samples were analyzed for TR-700 and the following pharmacokinetic parameters were calculated: C_max, t_max, AUC_0−∞, AUC_0−t λ_z, CL_sys, and plasma ${\mathsf{\text{t}}}_{1\text{/}2}$.

Results

Baseline eGFR ranged from 7 to 28 ml/minute/1.73 m² (including three subjects with eGFR <15 ml/minute/1.73 m²). The pharmacokinetics of TR-700 was essentially unchanged in subjects with advanced renal impairment relative to a matched control group. Approximately 8% lower AUC and nearly identical C_max values were observed in renal impaired subjects relative to matched controls, and other pharmacokinetic parameters were also similar between groups. See Table 1.

Table 1 Pharmacokinetic parameters of tedizolid in control and renal impaired subjects

Conclusion

The TR-700 plasma pharmacokinetic results from this study provide support that no dose adjustment is needed in subjects with advanced renal impairment.