An open-label study was conducted in adults with
schizophrenia at 37 sites in Japan. Patients were enrolled in either cohort 1 or 2. Patients in cohort 1 received 8-16 mg/day
blonanserin tablets for 6 weeks and then 40-80 mg/day
blonanserin patches for 52 weeks. The dose of
blonanserin patches was determined according to the dose of the
tablets. In cohort 2, every patient started from 40 mg/day and then 40-80 mg/day
blonanserin transdermal patches for 52 weeks. Both cohorts had 1-2 weeks of follow-up. Safety endpoints included the incidence of adverse events (AEs), treatment-related AEs, extrapyramidal AEs [also assessed using the change in
Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) score], the use of any concomitant antiparkinsonian drugs, and skin-related AEs, including skin irritation. Patients also underwent assessment of laboratory values including for serum
prolactin concentration, vital signs,
body weight, electrocardiographic (ECG) changes, and the corrected QT (QTc) interval. Suicidal ideation was assessed via the Columbia-Suicide Severity Rating Scale (C-SSRS) score. Efficacy was assessed via duration of
blonanserin transdermal patch treatment, Positive and Negative Syndrome Scale (PANSS) total and subscale scores, and Clinical Global Impression-Severity (CGI-S) scores. Other endpoints included total
Drug Attitude Inventory 10 (DAI-10) scores, EuroQol-5 Dimension (EQ-5D) effect values, and a patient questionnaire about the
dosage form.
RESULTS: A total of 223 patients with consents, 117 in cohort 1 and 106 in cohort 2 were included in the study. Of the 117 patients in cohort 1, 108 were treated with
blonanserin tablets, and 97 received
blonanserin patches and were included in the safety analysis set. In cohort 2, 103 of the 106 patients were treated with
blonanserin transdermal patches and were included in the safety analysis set. In total, 91 patients were male (45.5%). The mean age was 43.8 years. Discontinuation occurred in 40 patients (41.2%) in cohort 1 and 44 patients (42.7%) in cohort 2. Discontinuation resulted from AEs in 18.6% (cohort 1) and 11.7% (cohort 2) and from withdrawal of consent in 13.4% (cohort 1) and 20.4% (cohort 2), and seven patients overall discontinued due to skin reactions. AEs were reported in 174 patients (87.0%), and 13 serious AEs occurred in 12 patients (6.0%), of which six patients were in cohort 1 and six patients were in cohort 2. Serious AEs were six
schizophrenia (n = 6) and seven other AEs (n = 6), which included impulse-control disorder, fracture,
epistaxis,
asthma,
pneumonia aspiration,
pneumonia hemophilus, and
pneumonia. The most common AEs were
nasopharyngitis (n = 62, 31.0%), application site
erythema (n = 45, 22.5%), application site
pruritus (n = 23, 11.5%), and
akathisia (n = 20, 10.0%). AE incidence was similar in cohort 1 (84.5%) and cohort 2 (89.3%). Extrapyramidal and skin-related AEs were reported in 51 patients (25.5%) and 83 patients (41.5%), respectively. None of these AEs were serious. The mean change from baseline in total DIEPSS score at Week 52 {last observation carried forward [LOCF] (standard deviation [SD])} was -0.1 (1.55), indicating no marked effect. In terms of concomitant medications used in cohort 1 and cohort 2, 33.0% (32/97) and 22.3% (23/103) used antiparkinsonian drugs, respectively. The majority of skin-related AEs occurred early in treatment and were appropriately managed with topical
therapies. Of the patients who answered "No" to all C-SSRS categories at baseline (n = 129), 13 patients (10.1%) were evaluated as having emergence of suicidal ideation. Among patients who answered "No" to all C-SSRS suicidal behavior categories at baseline (n = 172), one (0.6%) was evaluated as having suicidal behavior during
blonanserin transdermal patch treatment. There were no clinically significant changes in laboratory tests or examinations, including
prolactin level, vital signs,
body weight, ECG, metabolism-related parameters, and QTc interval. The mean (SD) change in
body weight was - 0.04 (4.561) kg and - 0.67 (6.841) kg in cohort 1 and cohort 2, respectively. The mean changes from baseline in PANSS total score at Week 52 (LOCF [SD]) were - 0.1 [11.6] and - 3.4 [15.3] in cohort 1 and 2, respectively. PANSS scores did not change after switching from
tablet to patch formulation in cohort 1 and decreased over the 52 weeks of treatment with the
blonanserin patches. The mean change from baseline in CGI-S score at Week 52 (LOCF [SD]) was - 0.2 [1.03] in both cohorts combined. After 52 weeks of
blonanserin patch treatment, the total DAI-10 score increased or remained unchanged compared with baseline in 82 of the 129 patients (63.6%) for whom these data were available. In the intention-to-treat population of the combined cohorts (n = 200), the mean (SD) change from baseline in EQ-5D score at the last assessment was - 0.0365 (0.17603). Patients' attitudes to the
blonanserin transdermal patches were generally positive.
CONCLUSIONS: NCT02335658.