Efficacy and Safety of HP-3070, an Asenapine Transdermal System, in Patients With Schizophrenia: A Phase 3, Randomized, Placebo-Controlled Study.

OBJECTIVE: Asenapine is a second-generation antipsychotic used to treat individuals with schizophrenia. This phase 3 study assessed efficacy and safety of HP-3070, an asenapine transdermal system (patch), in adults with schizophrenia. METHODS: In this inpatient study, a 3- to 14-day screening/single-blind run-in washout period was followed by a 6-week double-blind period wherein patients with acutely exacerbated schizophrenia (DSM-5 criteria) were randomized 1:1:1 and received HP-3070 7.6 mg/24 h (n = 204), HP-3070 3.8 mg/24 h (n = 204), or placebo (n = 206). Primary endpoint was change from baseline (CFB) in week 6 Positive and Negative Syndrome Scale (PANSS) total score versus placebo; key secondary endpoint was CFB in week 6 Clinical Global Impression-Severity of Illness score versus placebo. Safety endpoints included treatment-emergent adverse events (TEAEs) and dermal assessments. RESULTS: Each of the HP-3070 doses demonstrated significant improvement versus placebo at week 6 for the primary and key secondary endpoints. Differences in the least-squares mean (LSM) (95% CI; adjusted P) of CFB for PANSS total scores were -4.8 (-8.06 to -1.64; adjusted P = .003) and -6.6 (-9.81 to -3.40; adjusted P < .001) for 7.6 mg/24 h and 3.8 mg/24 h, respectively. HP-3070 was well tolerated, with a systemic safety profile consistent with sublingual asenapine. Incidence of application site TEAEs was higher for HP-3070 (14.2%, 7.6 mg/24 h; 15.2%, 3.8 mg/24 h) versus placebo (4.4%). Discontinuations due to application site reactions or skin disorders (urticaria, pruritus) were infrequent (≤ 0.5% per treatment group). CONCLUSIONS: HP-3070 7.6 mg/24 h and 3.8 mg/24 h doses were efficacious and well tolerated. As the first transdermal antipsychotic patch available in the US, HP-3070 offers a novel treatment option for people with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02876900; EudraCT number: 2015-005134-21.

Patches: Established and Emerging Transdermal Treatments in Psychiatry.

Transdermal delivery is an alternative to oral routes of drug administration and has made considerable contributions to the treatment of various medical diseases. With the advent of new transdermal delivery technologies, higher numbers of medications are being approved for use as transdermal formulations. This route of administration has several innate advantages that have the potential to benefit various patient populations, including those with central nervous system disorders. The current review briefly outlines the history of transdermal medications, discusses the advantages and disadvantages of transdermal formulations, and examines the challenges and opportunities present for the use of transdermal treatments in psychiatry. Patients with psychiatric illnesses have many unmet needs that may be filled through the benefits gained from transdermal treatments, such as reduced dosing frequency, effective control of plasma medication concentrations, improved tolerability, ability to check compliance visually, and avoidance of first-pass hepatic metabolism. Established transdermal treatments for various psychiatric diseases are discussed followed by an introduction to therapies that are being developed as the first patch formulations for the treatment of schizophrenia. Hypothetical schizophrenia patient profiles are also outlined to aid providers in considering how transdermal treatments for this disease may fill unmet needs for specific patients. The evidence demonstrating the potential benefits of transdermal treatments in psychiatry presented in the current review should both encourage health care providers to consider how patients may benefit from transdermal alternatives and promote future innovation in the area of transdermal drug delivery for psychiatric disorders.