Participant Engagement and Symptom Improvement: Aripiprazole Tablets with Sensor for the Treatment of Schizophrenia

Jeffrey M Cochran,1 Hui Fang,2 Christophe Le Gallo,3 Timothy Peters-Strickland,4 Jean-Pierre Lindenmayer,5 J Corey Reuteman-Fowler6 1Medical & Real World Data Analytics, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 2Biostatistics, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 3Clinical Programming, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA; 4PPD, Inc., Wilmington, NC, USA; 5Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA; 6Global Clinical Development, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USACorrespondence: Jeffrey M Cochran, Medical & Real World Data Analytics, Otsuka Pharmaceutical Development & Commercialization, Inc., 508 Carnegie Center, Princeton, NJ, 08540, USA, Tel +1 609 535 9035, Email Jeffrey.Cochran@otsuka-us.comPurpose: A recent, phase 3b, mirror-image clinical trial of outpatients with schizophrenia found that use of aripiprazole tablets with sensor (AS; Abilify MyCite®, comprising an ingestible event-marker sensor embedded in aripiprazole tablets, wearable sensor patches, and a smartphone application) reduced the incidence of psychiatric hospitalizations relative to oral standard-of-care antipsychotics. This analysis explored the relationship between AS engagement by participants and changes in participant performance and symptom-severity measures assessed by clinical raters.Participants and Methods: This post hoc analysis used prospectively collected clinical data from a phase 3b clinical trial (NCT03892889). Outpatients had schizophrenia, were aged 18– 65 years, and had ≥ 1 psychiatric hospitalization in the previous 48 months. Participants were grouped by study completion status and a k-means clustering algorithm based on AS utilization, resulting in 3 groups: discontinued (discontinued AS before month 3 of the study); moderate engagement (completed 3 months, used AS intermittently); and high engagement (completed 3 months, used AS regularly). Baseline to end-of-study differences for the Clinical Global Impression Scale (Severity of Illness and Improvement of Illness scales), Personal and Social Performance Scale, and Positive and Negative Syndrome Scale were calculated.Results: A total of 277 outpatients were enrolled (discontinued, n = 164; moderate engagement, n = 63; high engagement, n = 50). All groups experienced symptom improvement from baseline to end-of-study, with significant changes in the more-engaged groups. Highly engaged participants showed significant improvement for all clinical scores and subscores (all P < 0.05) and demonstrated significantly more improvement in symptoms than participants with less engagement.Conclusion: Participants who completed 3 months of the study and had higher AS engagement experienced significantly greater improvement in their end-of-study clinical assessments versus participants who did not complete 3 months. Improvement may be related to more-consistent medication intake and better engagement with a digital health system.Keywords: digital medicine, medication ingestion, treatment utilization, Positive and Negative Syndrome Scal