Tralokinumab pharmacokinetics and tolerability when administered by different subcutaneous injection methods and rates

Abstract

Objective: Tralokinumab, administered as two 1-mL subcutaneous injections every 2 weeks, at the target dose 300 mg, has been shown to improve lung function in patients with asthma. This study evaluated the pharmacokinetic (PK) and tolerability profile of tralokinumab 300 mg when administered by different rates of subcutaneous injection, as part of a pilot investigation of new injection regimens.

Methods: This phase I study randomized 60 healthy adults to receive 300 mg tralokinumab, as two 1-mL subcutaneous injections, each delivered over 10 seconds, or one 2-mL injection delivered over 10 seconds (12 mL/min), 1 minute (2 mL/min), or 12 minutes (0.167 mL/min).

Results: No differences in the PK profile of tralokinumab were observed between cohorts. Immediately following injection, injection-site pain intensity (mean (SD)) was lowest following 0.167 mL/min injection (5.1 mm (8.0) via visual analog scale (VAS)) and greatest following 12 mL/min injection (41 mm (27.7) via VAS); with mean injection-site pruritus intensity low for all participants. Two types of local injection-site reactions were observed: erythema (58.3%) and hematoma/bleeding (18.3%). All treatment-emergent adverse events were mild.

Conclusions: Tralokinumab 300 mg is well tolerated, with comparable PK, when administered by a single 2-mL injection at different rates of subcutaneous injection vs. two 1-mL injections. .

Figures

Figure 1.. Study design. SC = subcutaneous.

Figure 2.. Experimental setup. The fluid path consisted of sterile, 510(k)-cleared components attached together via Luer connections. A Harvard syringe pump (HA3000W PHD Ultra infuse/withdraw syringe pump) (A), with a 10 mL plastic Luer-Lok™ syringe (BD) (B) and Microbore extension set (B. Braun) (C) attached were used to deliver tralokinumab at the required volume and flow rate. For cohorts 1 and 2, a 25-G × ½” Surflo® winged infusion set with 8” tubing (Terumo) (rigid needle) mimicking a standard subcutaneous injection was used (D). For cohorts 3 and 4, the Animas Inset™ infusion system with a 6-mm, 25-G soft cannula was used to mimic a on body SC delivery system (E).

Figure 3.. Participant disposition.

Figure 4.. Mean (SD) serum concentration-time profiles of tralokinumab by cohort (PK population).a PK = pharmacokinetic; SD = standard deviation. aThe participant in cohort 4 with extensive tralokinumab leakage was included in the patient population as detectable levels of tralokinumab were observed in the serum.

Figure 5.. Individual serum concentration-time profiles of tralokinumab by cohort (PK population). In cohort 4, data for the participant with extensive leakage is represented with an orange line. PK = pharmacokinetic.