LAUSR

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 (QTc). Bias‐corrected nonparametric two‐sided 90% confidence intervals (CIs) were derived for the mean predicted effect of BUP‐XR on QTc (ΔQTc) at therapeutic and supratherapeutic doses. Changes in QTc were associated with age, central vs. noncentral reading, sex, methadone, and barbiturates. The upper 90% CI of ΔQTc was 0.29, 0.67, and 1.34 ms at the steady‐state peak concentration (Cmax) 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.