Evaluation of the Effects of a Monthly Buprenorphine Depot Subcutaneous Injection on QT Interval During Treatment for Opioid Use Disorder

Extensive 12‐lead electrocardiogram monitoring and drug concentrations were obtained during development of BUP ‐ XR , a monthly subcutaneous injection for the treatment of opioid use disorder ( OUD ). Matched QT and plasma drug concentrations (11,925) from 1,114 subjects were pooled from 5 studies in OUD . A concentration‐ QT model was developed, which accounted for confounding factors (e.g., comedications) affecting heart rate and heart rate‐corrected QT interval ( QT c). Bias‐corrected nonparametric two‐sided 90% confidence intervals ( CI s) were derived for the mean predicted effect of BUP ‐ XR on QT c (Δ QT c) at therapeutic and supratherapeutic doses. Changes in QT c were associated with age, central vs. noncentral reading, sex, methadone, and barbiturates. The upper 90% CI of Δ QT c was 0.29, 0.67, and 1.34 ms at the steady‐state peak concentration (C max ) for 100, 300, and 2 × 300 mg doses, respectively. An effect of BUP ‐ XR on QT can be ruled out at therapeutic and supratherapeutic doses of BUP ‐ XR , after accounting for covariates that may influence heart rate and QT interval in OUD .