Pharmacokinetic Profile of the Asenapine Transdermal System (HP-3070)

PURPOSE/BACKGROUND: The asenapine transdermal system (HP-3070) is the first antipsychotic patch approved in the United States for treatment of adults with schizophrenia. METHODS/PROCEDURES: Three phase 1, open-label, randomized studies characterized the pharmacokinetic (PK) profile of HP-3070 by assessing its relative bioavailability compared with sublingual asenapine, its single-/multiple-dose PK and dose proportionality, and the effects of application site, ethnicity, and external heat on bioavailability. Two studies were conducted in healthy subjects, and 1 was conducted in adults with schizophrenia. FINDINGS/RESULTS: During single HP-3070 administration, asenapine concentrations increased gradually over approximately 12 hours and remained steady until the patch was removed 24 hours after application. Asenapine area under the curve values at HP-3070 3.8 and 7.6 mg/24 hours doses were similar to those for sublingual asenapine 5 and 10 mg twice-daily doses, respectively, whereas peak exposure (maximum observed plasma concentration) was significantly lower. During daily application of HP-3070, steady-state PK was reached within approximately 72 hours after initiating daily dosing and was characterized by peak-to-trough asenapine plasma concentration ratio of approximately 1.5. HP-3070 PK was dose proportional in the dose range studied, not affected by administration site, and similar across the studied ethnic groups. Application of external heat increased the rate of asenapine absorption (time to reach maximum observed plasma concentration) but did not significantly affect peak and total exposure. IMPLICATIONS/CONCLUSIONS: HP-3070 exhibited a dose-dependent PK profile unaffected by site of administration or ethnicity. HP-3070 showed a predictable absorption profile with limited variability, with an area under the curve similar to that of sublingual asenapine. Based on these PK metrics, HP-3070 steadily delivers asenapine with lower peaks and troughs than sublingual administration of asenapine.