Pharmacokinetic Bioequivalence of Enfuvirtide Using a Needle‐Free Device versus Standard Needle Administration

Study Objectives. To compare the relative bioavailability of enfuvirtide, a human immunodeficiency virus type 1 (HIV-1) fusion inhibitor, injected with the Biojector 2000 (B2000) needle-free device versus a 27-gauge half-inch needle-syringe; and to assess safety, tolerability and patient preference for the two devices. Design. Open-label, randomized, two-period crossover bioequivalence evaluation. Setting. Clinical research center. Patients. Twenty-seven adults with HIV-1 viral loads below 1000 copies/ml. Intervention. Each patient received enfuvirtide 90 mg subcutaneously with the B2000 and with the needle-syringe, with a 1-week washout between treatments. Measurements and Main Results. Twenty-six and 27 patients were included in the bioequivalence and safety analyses, respectively. Plasma enfuvirtide concentrations were measured at baseline and at several intervals after each injection. The B2000:needle-syringe ratios of maximum concentration (Cmax), area under the concentration-time curve from time zero extrapolated to infinity (AUC0–∞), and AUC from time zero to τ (dosing interval) (AUC0–τ) served as criteria for bioequivalence determination. The two drug delivery systems were considered bioequivalent if the 90% confidence intervals (CIs) for the ratios were within 0.8–1.25. Safety and tolerability were evaluated based on documentation of adverse events, graded laboratory toxicities, and local injection-site reactions. Patient surveys provided feedback on device preference. Ratios of Cmax, AUC0–τ, and AUC0–τ were 0.95 (90% CI 0.84–1.09), 0.99 (90% CI 0.93–1.05), and 0.99 (90% CI 0.93–1.05), respectively. The frequency of injection-site reactions was low, and severity was generally mild for both devices. Survey results showed 18 patients (69%) had a positive overall impression of the B2000 and 14 (54%) felt safer injecting with this device. Overall, 17 patients (65%) preferred the B2000 over the needle-syringe. Conclusion. Bioavailability of enfuvirtide with the B2000 and needle-syringe was equivalent based on Cmax, AUC0–τ, and AUC0–∞. Safety profiles and injection-site reactions were comparable between the devices, but patients preferred the B2000. Delivery of enfuvirtide with the B2000 is a feasible alternative to standard needle administration and warrants further evaluation.