Safety Evaluation in Iterative Development of Wearable Patches for Aripiprazole Tablets With Sensor: Pooled Analysis of Clinical Trials (Preprint)

Abstract

BACKGROUND Wearable sensors in digital health help facilitate real-time, point-of-care monitoring. However, wearable sensors may pose a risk for skin irritation through the use of adhesive patches. Little is known about how patient- and product-related factors impact the risk of skin irritation. Aripiprazole tablets with sensor (AS, Abilify MyCite®) is a digital medicine system indicated for the treatment of patients with schizophrenia, bipolar I disorder, and major depressive disorder. AS includes aripiprazole tablets with an embedded ingestible event marker, a wearable sensor attached to the skin through an adhesive patch, a smartphone app, and a web-based portal. To continuously improve the final product, successive iterations of sensor patches were developed, including RP4, which was replaced by DW5, followed by RW2. OBJECTIVE This analysis pooled safety data of clinical studies in adult participants using the RP4, DW5, and RW2 patches of AS and evaluated adverse events related to patch wear. METHODS We analyzed safety data from 6 long-term and 6 short-term studies in adults aged 18–65 years from May 2010 to August 2020. All studies evaluated safety, with short-term studies also specifically examining human factors associated with use of the components of AS. Healthy volunteers or patients with schizophrenia, bipolar I disorder, or major depressive disorder were enrolled; those who received ≥ 1 exposure to the patch component of AS were included in the safety analysis. Adverse events related to patch wear were evaluated: abrasions, blisters, dermatitis, discoloration, erythema, irritation, pain, pruritus, rash, and skin reactions were grouped as skin irritation events (SIEs). RESULTS The analysis included 763 participants (mean age 42.6 years, 47.1% White, 55% male). Participants were healthy volunteers (35.3%) or patients with schizophrenia (52.7%), bipolar I disorder (7.5%), or major depressive disorder (4.6%). Overall, 13.6% (n/N = 104/763) of the participants reported at least 1 SIE; any SIEs experienced were localized to the patch site. Incidence of SIEs decreased as the patch versions developed; ≥ 1 SIE was experienced by 18.1% (28/155), 14.2% (55/387), and 9.2% (28/306) of participants who used RP4, DW5, and RW2 patches, respectively. Incidence of SIE-related treatment discontinuation was low, reported in 1.9% (3/155), 3.1% (12/387), and 1.3% (4/306) of participants who used RP4, DW5, and RW2 patches, respectively. Incidence of SIEs was higher in long-term studies than in short-term studies (15.8% vs 8.8%), with 22.4%, 17.6%, and 5.6% of participants in long-term studies reporting ≥ 1 SIE for RP4, DW5, and RW2 patches, respectively. CONCLUSIONS The pooled safety analysis indicated that incidence of SIEs decreased as the patch versions evolved from RP4 through RW2. These results further suggest that information derived from reported adverse events may have informed product design and development, which improved both tolerability and wearability of successive products. CLINICALTRIAL 316-13-204, 316-13-205, 316-13-206A (NCT02091882), 316-13-206B (NCT02091882), 316-13-215 (NCT02722967), 316-14-220 (NCT02219009), 031-201-00186 (NCT03568500), 031-201-00266, 031-201-00301 (NCT03892889), 031-201-00383, 031-201-00420, 031-201-00469.