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 (C max ), area under the concentration‐time curve from time zero extrapolated to infinity (AUC 0–∞ ), and AUC from time zero to τ (dosing interval) (AUC 0–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 C max , AUC 0–τ , and AUC 0–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 C max , AUC 0–τ , and AUC 0–∞ . 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.